]> Neuroscience ontology derived from the SenseLab NeuronDB database. TODO: Some classes of receptors are not subclasses of Neuro_receptor, altough they should be. TODO: Refine definition of canonical neurons Angiotensin II receptor, type 2 AT2 Inner ear CN pyramidal (fusiform) cell ADORA2A Gene Thyrotropin-releasing hormone receptor TRH1 CNR1 Gene MC2R Gene Glutamate Olfactory cortex Alpha2 receptor Acetylcholine CXCR4 HRH2 Gene Calcium Activated Nonspecific cation channel I CAN current FSH receptor Follicle stimulating hormone receptor CNR2 Gene Retinal bipolar cell Purinergic receptor P2Y, G-protein coupled, 2 P2Y2 Calcium activated chloride current I Cl,Ca current edg3 NGFR Gene CRHR2 Gene Y6 Spinal motor neuron B2 Sensory receptor P2RX4 Gene Prostaglandin I2 (prostacyclin) receptor (IP) IP BRS3 Gene Kappa Opioid Peptide receptor TP Thromboxane A2 receptor GALNR3 Gene CN octopus cell Purinergic receptor P2X, ligand-gated ion channel, 1 P2X1 Epinephrine Hair cell (auditory) CYSLT1 Gene NTRK2 Gene MTNR1B Gene Nicotinic acetylcholine receptor Cochlear nucleus Adenylate cyclase activating polypeptide 1 (pituitary) receptor type I PAC1 PTGDR Gene CCR8 Chemokine (C-C motif) receptor 8 "Transient"; inactivating I A current PGR Gene Beta receptor Calcitonin receptor amylin EP3 Prostaglandin E receptor 3 (subtype EP3) Neurotransmitter / Neuromodulator Vasoactive intestinal peptide receptor 1 VPAC1 Glutamate receptor, metabotropic 6 mglur6 CCR3 Gene CRHR1 Gene Neuron with no axon F2RL2 Gene IL8RA Gene CCKAR Gene Mesencephalon Bradykinin receptor B1 B1 "Neither"; rapidly inactivating; threshold around -20 mV I N current PAR3 Coagulation factor II (thrombin) receptor-like 2 Gaseous receptor CCR9 Chemokine (C-C motif) receptor 9 Thalamic reticular neuron NTRK3 Gene CCR10 Formyl peptide receptor 1 fMLP Somatostatin receptor 5 sst5 Neuron with single dendrite or multipolar neuron Neurotrophic tyrosine kinase, receptor, type 2 trkB PTGER1 Gene ADRA1C Gene GAL1 GPR9 Gene CCR9 Gene Bombesin-like receptor 3 bb3+ CHRM1 Gene EDG5 Gene ET-B Endothelin receptor type B ADRA2C Gene MTNR1A Gene Tachykinin receptor 3 NK3 Principal neuron P2Y6 Pyrimidinergic receptor P2Y, G-protein coupled, 6 BBR2 Gene OXTR Gene ADORA3 Gene Acetylcholine receptor ADRA2B Gene A3 Adenosine A3 receptor Glutamate receptor, metabotropic 5 mglur5 Brain region ADRA2A Gene M5 receptor M5 NTSR1 Gene Neocortical pyramidal neuron deep V1b CO Norephinephrine Dorsal cochlear nucleus Dorsal cochlear nucleus Middle part of apical dendrite (Dam) Distal part of equivalent dendrite (Ded) MC4R Gene mGluR6 metabolic glutamate receptor mGluR5 metabolic glutamate receptor I IR,Q,h current Inward rectifier; "Queer"; activated by hyperpolarization/mixed cation current Olfactory receptor Histamine mGluR metabolic glutamate receptor Mu Opioid Peptide Alpha1 receptor Melanocortin 2 receptor (adrenocorticotropic hormone) MC2 C3a EDG1 Gene Visual motor Somatostatin receptor 1 sst1 Olfactory cortex pyramidal neuron V1a Arginine vasopressin receptor 1A SSTR2 Gene D1 receptor D1 Dopamine receptor D1 I Potassium current Muscarinic acetylcholine receptor Receptor P2RY4 Gene Histamine receptor H3 H3 Olfactory receptor neuron PAR4 Coagulation factor II (thrombin) receptor-like 3 P2X4 Purinergic receptor P2X, ligand-gated ion channel, 4 IL8RB Gene CN bushy cell Peptide P2Y1 MC1R Gene ADORA2B Gene CB2 Cannabinoid receptor 2 (macrophage) Retinal photoreceptor Proximal part of basal dendrite (Dbp) Neocortical basket cell Dentate Paleocortex Retina Calcitonin receptor calcitonin Adrenergic, alpha-1B-, receptor alpha 1B TACR3 Gene BB2 M1 receptor M1 Chemokine (C-C motif) receptor 3 CCR3 5-ht5B receptor Electrical current between two cells. Rectifying or non-rectifying types. I gap current Glucocorticoid p75 NPR2 Gene Opsin (photoreceptor) Chemokine (C-C motif) receptor 6 CCR6 Basal dendrite Serotonin mglur1 HTR2B Gene HTR5A Gene DRD5 Gene NO trh2_ edg4 Endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor, 4 EDNRA Gene TBXA2R Gene MT2 Peroxisome proliferator-activated receptor gamma PPAR-gama BLR1 Gene I CNG current Cyclic-Nucleotide Gated nonspecific cation channel CXCR3 PAR1 Coagulation factor II (thrombin) receptor Olfactory cortex interneuron superficial F2RL1 Gene HTR2C Gene Hair cell (vestibular) CCKBR Gene alpha 2C Adrenergic, alpha-2C-, receptor PTGER2 Gene "Long-lasting"; slowly inactivating; threshold around -20 mV I L high threshold current Olfactory cortex interneuron deep GALNR2 Gene Adenosine A1 receptor A1 Diencephalon Diencephalon HRH3 Gene Neuronal receptor NTSR2 Gene SSTR4 Gene HTR2A Gene AGTR1 Gene ANPA Natriuretic peptide receptor A/guanylate cyclase A (atrionatriuretic peptide receptor A) DRD3 Gene Histamine receptor BLT M2 receptor M2 gal3 CHRM2 Gene alpha 2B NTRK1 Gene Kainate receptor NA Gene Neostriatum Progesterone Progesterone receptor EDNRB Gene Dentate granule cell Zn2+ Androgen Androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease) Apical dendrite trkC NPY6R Gene mglur7 Interneuron Olfactory bulb periglomerular cell CCR2 Gene Olfactory epithelium HTR4 Gene CXCR5 Burkitt lymphoma receptor 1, GTP binding protein (chemokine (C-X-C motif) receptor 5) GABA CRF1 Corticotropin releasing hormone receptor 1 Antennal Lobe CCR8 Gene Dendrite PPARA Gene Olfactory projection neuron Segment I Na,p current Persistent (plateau); non-inactivating; TTX-resistant BB1 P2RX3 Gene EDG2 Gene 5-HT5 receptor Adrenergic receptor ADRB3 Gene NPR1 Gene Mineralocorticoid I T low threshold current "Transient"; rapidly inactivating, threshold negative to -65mV Cochlea P2X3 Purinergic receptor P2X, ligand-gated ion channel, 3 5-HT1 receptor Basal ganglia 5-hydroxytryptamine (serotonin) receptor 6 5-ht6 receptor Soma Axon GALNR Gene mglur4 Dopamine receptor D3 D3 SSTR1 Gene GRM4 Gene Mechanoreceptor Retinal ganglion cell CCR2 Peptide receptor PTGER3 Gene CCR1 Gene Nigral dopaminergic cell Prostaglandin E receptor 4 (subtype EP4) EP4 Distal part of basal dendrite (Dbd) CCR11 5-ht1E 5-hydroxytryptamine (serotonin) receptor 1E ADORA1 Gene P2RX1 Gene Olfactory bulb Somatostatin receptor 2 sst2 mGluR1 metabolic glutamate receptor Adrenergic, alpha-2A-, receptor alpha 2A OPRD Gene gal2 P2RX2 Gene Cerebellum CXCR2 Interleukin 8 receptor, beta mglur8 Glutamate receptor, metabotropic 8 Hippocampus Melatonin receptor 1A MT1 GRM8 Gene GPR2 Gene CCR5 5-HT7 receptor 5-hydroxytryptamine (serotonin) receptor 7 (adenylate cyclase-coupled) C3AR1 Gene F2RL3 Gene Metencephalon mGluR3 metabolic glutamate receptor CCR4 Gene HRH1 Gene Compartment CRF2 Corticotropin releasing hormone receptor 2 BDKRB1 Gene CHRM5 Gene PTGFR Gene NMDA receptor VIPR1 Gene Cholecystokinin B receptor CCK2 Anterior ventral cochlear nucleus TACR2 Gene I Chloride current D2 receptor D2 Dopamine receptor D2 HTR3 Gene Ions Thalamic relay neuron N/OFQ receptor I Na,t current "Transient"; rapidly inactivating MC5R Gene NTS1 5-hydroxytryptamine (serotonin) receptor 2C 5-HT2C LTB4R Gene 5-HT4 receptor 5-hydroxytryptamine (serotonin) receptor 4 Gabrg1 Gene Dynorphin P2Y4 Dopaminergic receptor CB1 mGluR8 metabolic glutamate receptor GRL Gene Gene Adrenergic, beta-3-, receptor beta 3 Equivalent dendrite HTR1F Gene CCR7 Gene ADRB1 Gene Neocortical pyramidal neuron superficial AMPA receptor AMPA Glutamate receptor, ionotrophic, AMPA 3 Glycine edg5 Dynorphin receptor A2A Adenosine A2a receptor alpha 1A receptor alpha 1D Adrenergic, alpha-1D-, receptor Dopamine ADRA1B Gene Neuron with apical and basal dendrites TSHR Gene LHCGR Gene OPRK Gene Amino acid receptor HTR1D Gene C5a Alpha receptor beta 2 mglur3 CALCR Gene EP1 Prostaglandin E receptor 1 (subtype EP1), 42kDa Monoamine receptor I A, slow current Slowly inactivating "delay" current I K(D) Tachykinin receptor 2 NK2 Axon hillock (AH) Includes BK, IK, SK, and I AHP currents; K current activated by increases in [Ca2+]i; voltage dependence varies I K,Ca current Gases VPAC2 AR Gene CHRM4 Gene MC3R Gene GRM5 Gene Monoamine CCR6 Gene D4 Dopamine receptor D4 P2RY2 Gene Cerebellar granule cell Y4 CysLT1 GRM6 Gene MC5 Melanocortin 5 receptor NPY1R Gene Contributes to neuronal resting "leak"conductance I K,leak current Archicortex Middle part of equivalent dendrite (Dem) Endothelial differentiation, sphingolipid G-protein-coupled receptor, 1 edg1 GABA receptor Gamma-aminobutyric acid (GABA) B receptor, 1 GABA-B receptor GabaB SSTR5 Gene FP DRD2 Gene ADRB2 Gene Activated by strong depolarization; delayed rectifier I K current Proximal part of apical dendrite (Dap) OPRM Gene Amino acid 5-HT2A P2RY1 Gene Neuron P2X2 Purinergic receptor P2X, ligand-gated ion channel, 2 EDG3 Gene DP Prostaglandin D2 receptor (DP) I Sodium GRM7 Gene Axon terminal (T) Neostriatal cholinergic interneuron CA1 pyramidal neuron Spinal Ia interneuron AGTR2 Gene Distal part of apical dendrite (Dad) DRD1 Gene 5-ht1F 5-hydroxytryptamine (serotonin) receptor 1F BDKRB2 Gene ADRA1D Gene Includes both p-type and q-type currents I p,q current 5-HT3 receptor Melanocortin 4 receptor MC4 Neurotensin receptor 2 nts2 Neuron current gria3 Gene sst4 TACR1 Gene Natriuretic peptide receptor B/guanylate cyclase B (atrionatriuretic peptide receptor B) ANPB CCR5 Gene FSHR Gene Posterior ventral cochlear nucleus AVPR2 Gene V2 Neuropeptide Y receptor Y1 Y1 Dopamine receptor D5 D5 Ventral horn CCK1 Cholecystokinin A receptor 5-HT1B 5-hydroxytryptamine (serotonin) receptor 1B HTR7 Gene GRM3 Gene CCR7 Chemokine (C-C motif) receptor 7 OPRL Gene Substantia nigra PTGER4 Gene EDG4 Gene Myelencephalon NO receptor P2RY11 Gene HTR1B Gene GABBR1 Gene MLR Gene Thalamus Cholinergic receptor, muscarinic 3 M3 receptor M3 TSH receptor Thyroid stimulating hormone receptor Glutamate receptor ADCYAP1R1 Gene Oxytocin receptor OT mglur1 Gene PPARD Gene Zn2+ receptor Cholinergic receptor, muscarinic 4 M4 receptor M4 NPY2R Gene AVPR1A Gene trkA Neurotrophic tyrosine kinase, receptor, type 1 Interleukin 8 receptor, alpha CXCR1 Gamma-aminobutyric acid (GABA) A receptor, gamma 1 GABA-A receptor GabaA Glutamate receptor, metabotropic 2 mglur2 Proximal part of equivalent dendrite (Dep) P2RY6 Gene BBR1 Gene Middle part of basal dendrite (Dbm) AVPR3 Gene HTR1E Gene MC3 Melanocortin 3 receptor 5-HT1A 5-hydroxytryptamine (serotonin) receptor 1A Vestibular organ Y5 Neostriatal spiny neuron 5-hydroxytryptamine (serotonin) receptor 2B 5-HT2B Coagulation factor II (thrombin) receptor-like 1 PAR2 edg2 Endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor, 2 Cerebellar purkinje cell PTGIR Gene HTR1A Gene FPR1 Gene CHRM3 Gene trhr2 Gene 5-hydroxytryptamine (serotonin) receptor 1D 5-HT1D I Calcium current Chemokine (C-C motif) receptor 1 CCR1 5-ht5A receptor 5-hydroxytryptamine (serotonin) receptor 5A 5-HT2 receptor MC1 Melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) AT1 VIPR2 Gene Y2 Neuropeptide Y receptor Y2 I M current Activated by depolarization above -65 mV; slow, weak and non-inactivating; blocked by ligands like acetylcholine acting through muscarinic (M) receptors Luteinizing hormone/choriogonadotropin receptor LSH receptor Prostaglandin E receptor 2 (subtype EP2), 53kDa EP2 Spinal cord mGluR7 metabolic glutamate receptor PPARG Gene I Mixed current HTR6 Gene CA1 oriens alveus interneuron Neocortex Olfactory bulb granule cell GRM2 Gene F2R Gene H1 receptor H1 Histamine receptor H1 Glycine receptor Histamine receptor H2 H2 receptor H2 NPY5R Gene Molecule, molecular complex or ion CO receptor NK1 mGluR2 metabolic glutamate receptor Serotonin receptor Olfactory bulb mitral cell Axon shaft (T) TRHR Gene DRD4 Gene p2y11 PPAR-beta Peroxisome proliferator-activated receptor delta CA3 pyramidal neuron htr5b Gene Forebrain PPAR-alpha Peroxisome proliferator-activated receptor alpha beta 1 NPY4R Gene A2B Adenosine A2b receptor Somatostatin receptor 3 sst3 SSTR3 Gene Delta Opioid Peptide ET-A Endothelin receptor type A mGluR4 metabolic glutamate receptor CXCR4 Gene C5AR Gene Ion receptor Chemokine (C-C motif) receptor 4 CCR4 Relates a protein to the gene that encodes the protein. protein is gene product of cites evidence source has currents indentified by Pubmed ID has transmitter has peptide sequence described by has receptors The subcellular distribution and biophysical properties of this current were studied in cell-attached patches. The basal dendrites were practically devoid of this conductance [213]. The subcellular distribution and biophysical properties of this current were studied in cell-attached patches. The basal dendrites were practically devoid of this conductance [213]. The rate of NMDAR channel opening was studied in response to depolarisations at different times after brief 1 ms and sustained 4.6 s applications of glutamate to nucleated patches from neocortical pyramidal neurons [478]. The distribution of GABAA and GABAB receptors was studied with patch-clamp recording in combination with infrared-guided laser stimulation to release GABA photolytically. The data suggest that relatively more GABAA receptors are located at the apical dendrite and relatively more GABAB receptors near the soma [217]. The distribution of GABAA and GABAB receptors was studied with patch-clamp recording in combination with infrared-guided laser stimulation to release GABA photolytically. The data suggest that relatively more GABAA receptors are located at the apical dendrite and relatively more GABAB receptors near the soma [217]. Immunolabeling was observed in soma and dendrites of layer V pyramidal cells in the frontal cortex [219]. This persistant conductance may be activated by the NMDA receptor depolarization, providing a mechanism for graded, voltage dependent EPSP amplification [59]. The subcellular distribution and biophysical properties of this current were studied in cell-attached patches. Up to approximately 400um from the soma a low density of channels was found, with a 20-fold increase in the apical distal dendrite. The findings suggest that integration of synaptic input to the apical tuft and the basal dendrites occurs spatially independently due to the high Ih channel density in the apical tuft that increases the electrotonic distance between these two compartments in comparison to a passive dendrite [213]. A linear increase has been found 9 pA/100um in the density of these channels with distance from soma. It was suggested that this generates site independence of EPSP time course [214]. Types and distribution of voltage-gated K+ channels in the soma and apical dendrites were studied in acute brain slices [179]. The amplitude of ensemble K+ currents in cell-attached patches decreased along the apical dendrite as the distance from the soma increased, with a slope of -0.9 +/- 0.3 pA per 100um. In nucleated outside-out patches from soma in acute slices of sensorimotor cortex from 13- to 15-day-old Wistar rats some patches contained only I-A-like channels, other contained only IK-like channels that did not inactivate or inactivated slowly, and the remainder contained mixtures of both types. The amount of IA and IK depended weakly on distance along the primary apical dendrite from the soma. The amplitude of IA increased, while the amplitude of IK decreased [227][228]. using whole-cell patch-clamp recordings from freshly dissociated mouse neocortical pyramidal neurons showed that Ca2+-dependent K+ currents were activated by Ca2+ entry through both N- and L-type channels [480]. Dual patch-clamp recordings showed that Ca-activated K+ BK channels were not triggered by neuronal action potentials in normal slices and only opened as neuronal responses deteriorated smaller or absent spikes and in a spike-independent manner, suggesting that BK channels may activate only in pathological conditions [220]. Intracellular recordings from sensorimotor cortex suggested that what activate IKCa persistently would not be calcium but some biochemical modification triggered by NMDA receptor activation [221]. Ca2+-activated K+ currents were studied using whole-cell patch-clamp recordings from freshly dissociated mouse neocortical pyramidal neurons [480]. using whole-cell patch-clamp recordings from freshly dissociated mouse neocortical pyramidal neurons showed that Ca2+-dependent K+ currents were activated by Ca2+ entry through both N- and L-type channels [480]. It has been suggested that the pharmacologically separable components of the HVA current in these neurons do not differ significantly in kinetics [285]. Using calcium imaging, calcium waves in layer 2/3 and layer 5 neocortical somatosensory pyramidal neurons were examined in slices from 2- to 8-week-old rats [481]. Types and distribution of voltage-gated K+ channels in the soma and apical dendrites were studied in acute brain slices [179]. The amplitude of ensemble K+ currents in cell-attached patches decreased along the apical dendrite as the distance from the soma increased, with a slope of -0.9 +/- 0.3 pA per 100um. In nucleated outside-out patches from soma in acute slices of sensorimotor cortex from 13- to 15-day-old Wistar rats some patches contained only I-A-like channels, other contained only IK-like channels that did not inactivate or inactivated slowly, and the remainder contained mixtures of both types. The amount of IA and IK depended weakly on distance along the primary apical dendrite from the soma. The amplitude of IA increased, while the amplitude of IK decreased [227][228]. Dual whole-cell recordings in acute slices showed that kainate receptors located on presynaptic interneuron terminals can be activated by glutamate released from the somatodendritic compartment of the postsynaptic pyramidal cells [215]. The subcellular distribution and biophysical properties of this current were studied in cell-attached patches. The basal dendrites were practically devoid of this conductance [213]. Immunolabeling was observed in soma and dendrites of layer V pyramidal cells in the frontal cortex [219]. The distribution of GABAA and GABAB receptors was studied with patch-clamp recording in combination with infrared-guided laser stimulation to release GABA photolytically. The data suggest that relatively more GABAA receptors are located at the apical dendrite and relatively more GABAB receptors near the soma [217]. Recordings using infrared-guided laser stimulation combined with whole cell recordings revealed a highly nonuniform distribution. Hot spots, with amplitude and integral of glutamate-evoked responses three times larger than responses evoked at neighboring sites, were detected. It appeared that the larger responses evoked resulted from an increase in activation of both AMPA and NMDA receptors. There was no correlation with branch points [300]. The distribution of GABAA and GABAB receptors was studied with patch-clamp recording in combination with infrared-guided laser stimulation to release GABA photolytically. The data suggest that relatively more GABAA receptors are located at the apical dendrite and relatively more GABAB receptors near the soma [217]. Types and distribution of voltage-gated K+ channels in the soma and apical dendrites were studied in acute brain slices [179]. The amplitude of ensemble K+ currents in cell-attached patches decreased along the apical dendrite as the distance from the soma increased, with a slope of -0.9 +/- 0.3 pA per 100um. In nucleated outside-out patches from soma in acute slices of sensorimotor cortex from 13- to 15-day-old Wistar rats some patches contained only I-A-like channels, other contained only IK-like channels that did not inactivate or inactivated slowly, and the remainder contained mixtures of both types. The amount of IA and IK depended weakly on distance along the primary apical dendrite from the soma. The amplitude of IA increased, while the amplitude of IK decreased [227][228]. Types and distribution of voltage-gated K+ channels in the soma and apical dendrites were studied in acute brain slices [179]. The amplitude of ensemble K+ currents in cell-attached patches decreased along the apical dendrite as the distance from the soma increased, with a slope of -0.9 +/- 0.3 pA per 100um. In nucleated outside-out patches from soma in acute slices of sensorimotor cortex from 13- to 15-day-old Wistar rats some patches contained only I-A-like channels, other contained only IK-like channels that did not inactivate or inactivated slowly, and the remainder contained mixtures of both types. The amount of IA and IK depended weakly on distance along the primary apical dendrite from the soma. The amplitude of IA increased, while the amplitude of IK decreased [227][228]. The developmental evolution of Ca-dependent spikes in the tuft was investigated using simultaneous somatic and dendritic recordings [182]. Using calcium imaging, calcium waves in layer 2/3 and layer 5 neocortical somatosensory pyramidal neurons were examined in slices from 2- to 8-week-old rats [481]. Ih conductance causes voltage attunuation and is more concentrated in dendrites than in soma [431]. The subcellular distribution and biophysical properties of this current were studied in cell-attached patches. Up to approximately 400um from the soma a low density of channels was found, with a 20-fold increase in the apical distal dendrite. The findings suggest that integration of synaptic input to the apical tuft and the basal dendrites occurs spatially independently due to the high Ih channel density in the apical tuft that increases the electrotonic distance between these two compartments in comparison to a passive dendrite [213]. A linear increase has been found 9 pA/100um in the density of these channels with distance from soma. It was suggested that this generates site independence of EPSP time course [214]. This persistant conductance may be activated by the NMDA receptor depolarization, providing a mechanism for graded, voltage dependent EPSP amplification [59]. Many authors have described the activation of dendritic voltage activated Ca channels [58]. Numerous authors e.g., [78]; Benardo et al 1982; [79] have provided evidence for active properties. Dual patch recordings show backpropagating impulses [43]. [184] The distribution of GABAA and GABAB receptors was studied with patch-clamp recording in combination with infrared-guided laser stimulation to release GABA photolytically. The data suggest that relatively more GABAA receptors are located at the apical dendrite and relatively more GABAB receptors near the soma [217]. The distribution of GABAA and GABAB receptors was studied with patch-clamp recording in combination with infrared-guided laser stimulation to release GABA photolytically. The data suggest that relatively more GABAA receptors are located at the apical dendrite and relatively more GABAB receptors near the soma [217]. Immunolabeling was observed in soma and dendrites of layer V pyramidal cells in the frontal cortex [219]. Recordings using infrared-guided laser stimulation combined with whole cell recordings revealed a highly nonuniform distribution. Hot spots, with amplitude and integral of glutamate-evoked responses three times larger than responses evoked at neighboring sites, were detected. It appeared that the larger responses evoked resulted from an increase in activation of both AMPA and NMDA receptors. There was no correlation with branch points [300]. The subcellular distribution and biophysical properties of this current were studied in cell-attached patches. Up to approximately 400um from the soma a low density of channels was found, with a 20-fold increase in the apical distal dendrite. The findings suggest that integration of synaptic input to the apical tuft and the basal dendrites occurs spatially independently due to the high Ih channel density in the apical tuft that increases the electrotonic distance between these two compartments in comparison to a passive dendrite [213]. A linear increase has been found 9 pA/100um in the density of these channels with distance from soma. It was suggested that this generates site independence of EPSP time course [214]. Types and distribution of voltage-gated K+ channels in the soma and apical dendrites were studied in acute brain slices [179]. The amplitude of ensemble K+ currents in cell-attached patches decreased along the apical dendrite as the distance from the soma increased, with a slope of -0.9 +/- 0.3 pA per 100um. In nucleated outside-out patches from soma in acute slices of sensorimotor cortex from 13- to 15-day-old Wistar rats some patches contained only I-A-like channels, other contained only IK-like channels that did not inactivate or inactivated slowly, and the remainder contained mixtures of both types. The amount of IA and IK depended weakly on distance along the primary apical dendrite from the soma. The amplitude of IA increased, while the amplitude of IK decreased [227][228]. This persistant conductance may be activated by the NMDA receptor depolarization, providing a mechanism for graded, voltage dependent EPSP amplification [59]. Numerous authors e.g., [78]; Benardo et al 1982; [79] have provided evidence for active properties. Dual patch recordings show backpropagating impulses [43]. [184] Dendritic fluorescence imaging showed that Ca2+ channels of several subtypes mediated the AP-evoked fluorescence transient in the proximal 100-170 microns apical dendrite. The fluorescence resulted from Ca2+ entry through L, N, and P-type channels, and through Ca2+ channels R-type not sensitive to L-, N- and P-type Ca2+ channel blockers [222]. Dendritic fluorescence imaging showed that Ca2+ channels of several subtypes mediated the AP-evoked fluorescence transient in the proximal 100-170 microns apical dendrite. The fluorescence resulted from Ca2+ entry through L, N, and P-type channels, and through Ca2+ channels R-type not sensitive to L-, N- and P-type Ca2+ channel blockers [222]. Using calcium imaging, calcium waves in layer 2/3 and layer 5 neocortical somatosensory pyramidal neurons were examined in slices from 2- to 8-week-old rats [481]. Many authors have described the activation of dendritic voltage activated Ca channels [58]. Types and distribution of voltage-gated K+ channels in the soma and apical dendrites were studied in acute brain slices [179]. The amplitude of ensemble K+ currents in cell-attached patches decreased along the apical dendrite as the distance from the soma increased, with a slope of -0.9 +/- 0.3 pA per 100um. In nucleated outside-out patches from soma in acute slices of sensorimotor cortex from 13- to 15-day-old Wistar rats some patches contained only I-A-like channels, other contained only IK-like channels that did not inactivate or inactivated slowly, and the remainder contained mixtures of both types. The amount of IA and IK depended weakly on distance along the primary apical dendrite from the soma. The amplitude of IA increased, while the amplitude of IK decreased [227][228]. Dendritic fluorescence imaging showed that Ca2+ channels of several subtypes mediated the AP-evoked fluorescence transient in the proximal 100-170 microns apical dendrite. The fluorescence resulted from Ca2+ entry through L, N, and P-type channels, and through Ca2+ channels R-type not sensitive to L-, N- and P-type Ca2+ channel blockers [222]. The distribution of GABAA and GABAB receptors was studied with patch-clamp recording in combination with infrared-guided laser stimulation to release GABA photolytically. The data suggest that relatively more GABAA receptors are located at the apical dendrite and relatively more GABAB receptors near the soma [217]. Recordings using infrared-guided laser stimulation combined with whole cell recordings revealed a highly nonuniform distribution. Hot spots, with amplitude and integral of glutamate-evoked responses three times larger than responses evoked at neighboring sites, were detected. It appeared that the larger responses evoked resulted from an increase in activation of both AMPA and NMDA receptors. There was no correlation with branch points [300]. The distribution of GABAA and GABAB receptors was studied with patch-clamp recording in combination with infrared-guided laser stimulation to release GABA photolytically. The data suggest that relatively more GABAA receptors are located at the apical dendrite and relatively more GABAB receptors near the soma [217]. Immunolabeling was observed in soma and dendrites of layer V pyramidal cells in the frontal cortex [219]. Types and distribution of voltage-gated K+ channels in the soma and apical dendrites were studied in acute brain slices [179]. The amplitude of ensemble K+ currents in cell-attached patches decreased along the apical dendrite as the distance from the soma increased, with a slope of -0.9 +/- 0.3 pA per 100um. In nucleated outside-out patches from soma in acute slices of sensorimotor cortex from 13- to 15-day-old Wistar rats some patches contained only I-A-like channels, other contained only IK-like channels that did not inactivate or inactivated slowly, and the remainder contained mixtures of both types. The amount of IA and IK depended weakly on distance along the primary apical dendrite from the soma. The amplitude of IA increased, while the amplitude of IK decreased [227][228]. Types and distribution of voltage-gated K+ channels in the soma and apical dendrites were studied in acute brain slices [179]. The amplitude of ensemble K+ currents in cell-attached patches decreased along the apical dendrite as the distance from the soma increased, with a slope of -0.9 +/- 0.3 pA per 100um. In nucleated outside-out patches from soma in acute slices of sensorimotor cortex from 13- to 15-day-old Wistar rats some patches contained only I-A-like channels, other contained only IK-like channels that did not inactivate or inactivated slowly, and the remainder contained mixtures of both types. The amount of IA and IK depended weakly on distance along the primary apical dendrite from the soma. The amplitude of IA increased, while the amplitude of IK decreased [227][228]. Numerous authors e.g., [78]; Benardo et al 1982; [79] have provided evidence for active properties. Dual patch recordings show backpropagating impulses [43]. [184] This persistant conductance may be activated by the NMDA receptor depolarization, providing a mechanism for graded, voltage dependent EPSP amplification [59]. Dendritic fluorescence imaging showed that Ca2+ channels of several subtypes mediated the AP-evoked fluorescence transient in the proximal 100-170 microns apical dendrite. The fluorescence resulted from Ca2+ entry through L, N, and P-type channels, and through Ca2+ channels R-type not sensitive to L-, N- and P-type Ca2+ channel blockers [222]. Dendritic fluorescence imaging showed that Ca2+ channels of several subtypes mediated the AP-evoked fluorescence transient in the proximal 100-170 microns apical dendrite. The fluorescence resulted from Ca2+ entry through L, N, and P-type channels, and through Ca2+ channels R-type not sensitive to L-, N- and P-type Ca2+ channel blockers [222]. Dendritic fluorescence imaging showed that Ca2+ channels of several subtypes mediated the AP-evoked fluorescence transient in the proximal 100-170 microns apical dendrite. The fluorescence resulted from Ca2+ entry through L, N, and P-type channels, and through Ca2+ channels R-type not sensitive to L-, N- and P-type Ca2+ channel blockers [222]. Using calcium imaging, calcium waves in layer 2/3 and layer 5 neocortical somatosensory pyramidal neurons were examined in slices from 2- to 8-week-old rats [481]. The subcellular distribution and biophysical properties of this current were studied in cell-attached patches. Up to approximately 400um from the soma a low density of channels was found, with a 20-fold increase in the apical distal dendrite. The findings suggest that integration of synaptic input to the apical tuft and the basal dendrites occurs spatially independently due to the high Ih channel density in the apical tuft that increases the electrotonic distance between these two compartments in comparison to a passive dendrite [213]. A linear increase has been found 9 pA/100um in the density of these channels with distance from soma. It was suggested that this generates site independence of EPSP time course [214]. Many authors have described the activation of dendritic voltage activated Ca channels [58]. Dual whole-cell recordings in acute slices showed that kainate receptors located on presynaptic interneuron terminals can be activated by glutamate released from the somatodendritic compartment of the postsynaptic pyramidal cells [215]. Dual whole-cell recordings in connected cell pairs suggested that attenuation of local horizontal excitation by dopamine is through D1 actions at a presynaptic site [218]. From cerebral cortex [45]. P2 Amputation of the apical dendrite approximately 30 micron from the soma, while simultaneously recording the slow AHP whole cell current at the soma, depressed the sAHP amplitude by only approximately 30% compared with control. Somatic cell-attached and nucleated patches did not contain sAHP current. Amputation of the axon about 20um from the soma had little effect on the amplitude of the sAHP. By this process of elimination, it is suggested that sAHP channels may be concentrated in the basal dendrites of CA1 pyramids [192]. --- --- Extracelluar ACPD an mGluR agonist application to apical or basal dendrites of CA1 pyramidal neurons causes local increases in calcium concentration that propagate throughout the cell, as measured by simultaneous whole cell recording and confocal microscopy with calcium imaging [146], suggesting the presence of mGluRs. [147] provide evidence that activation of these receptors is necessary for LTP induction . The way that different parts of a neuron carry out multiple information processing roles is illustrated by the CA1 pyramidal cell in the hippocampus. The authors used 2-photon microscopy to obtain high resolution images of calcium signals in the apical dendrites while activating Schaffer collateral inputs to induce long-term potentiation LTP of different durations. Short-duration LTP LTP 1 was associated with Ca increase in dendritic spines, due to activation of NMDA receptors and local ryanodine receptors RyRs. Intermediate duration LTP LTP 2 was associated with Ca increase in dendritic branches, due to activation of NMDA receptors and local IP3 receptors IP3Rs. For Ca increase in long duration LTP LTP3, see Ca channels in CA1 pyramidal cell apical dendrite. The authors conclude that "selective induction of different forms of LTP is achieved via spatial segregation of functionally distinct calcium signals"[540]. The Schaeffer collateral/commissural pathway elicits EPSPs in CA1 that have an NMDA-receptor mediated component that can be blocked by APV under certain experimental circumstances such as low bath Mg+ levels. Many authors have suggested that NMDA receptors may be involved in long-term potentiation in this region. Reviewed in [142]. EM showed colocalization at axodendritic asymmetric synapses within the CA1 subfield of rat hippocampus. AMPA/NMDA receptor colocalization was found in non-GABAergic dendritic shafts as well as dendritic spines, suggesting that excitatory neuronal transmission in CA1 neurons may generally involve activation of both NMDA and AMPA receptor subunits at a single synapse [250]. The Schaeffer collateral/commissural pathway elicits EPSPs in CA1 that have a large AMPA receptor-mediated component that can be blocked by CNQX [145]. Reviewed in [142].EM showed colocalization at axodendritic asymmetric synapses within the CA1 subfield of rat hippocampus. AMPA/NMDA receptor colocalization was found in non-GABAergic dendritic shafts as well as dendritic spines, suggesting that excitatory neuronal transmission in CA1 neurons may generally involve activation of both NMDA and AMPA receptor subunits at a single synapse [250]. Using outside-out patches and a fast application system the properties and distribution of synaptic glutamate receptors an approximately twofold increase in AMPA-mediated current was observed in the dendritic region that receives a uniform density of Schaffer collateral input 100-250um from soma [299]. [183] Ca fluorescence imaging shows that application of L-channel antagonists reduces the Ca influx associated with backpropagating action potentials, and has a significantly greater effect in the proximal dendrites than in more distal dendrites [143]. Patch recordings yield an approximate channel density of 7 pS/micron^2 in juvenile rats ] 4 wks of age, rising to 10 pS/micron^2 in older rats. Ca channel density was similar in other dendritic compartments, and in general lower than Na channel density [140]. However, in a few apical patches the channel density was increased X 3, which could indicate channel clustering. Ca fluorescence imaging shows that application of T-channel antagonists reduces the Ca influx associated with backpropagating action potentials, and has a two-fold greater effect in the dendrites than in the soma [143]. A D-type potassium current is involved in dendritic calcium spikes initiation and repolarization [438]. "action potential-mediated depolarization can...result in the elevation of dendritic intracellular Ca concentration Regehr et al 1989, [76], which is important for the induction of long term changes in synaptic strength" [57]. Membrane patches recorded in the cell-attached patch configuration from the soma and apical dendrites revealed an Ih that increased over sixfold from soma to distal dendrites. Ih demonstrated a mixed Na+-K+ conductance and was sensitive to low concentrations of external CsCl. As a result of Ih the propagation of subthreshold voltage transients is directionally specific. The elevated dendritic Ih density decreases EPSP amplitude and duration and reduces the time window over which temporal summation takes place [187]. A-current is reduced in the presence of beta-amyloid receptors[517]. Patch-clamp recordings reveal a high density of A-type K channels in the dendritic tree, which increases with distance from the soma [144]. A shift toward more depolarized potentials of the activation curve has also been observed in mid and distal dendrites more than 100um [144]. These channels "prevent initiation of an action potential in the dendrites, limit the backpropagation of action potentials into the dendrites, and reduce excitatory synaptic events" [144]. Single action potential backpropagations show dichotomy of either strong attenuation 26-42% or weak attenuation 71-87%. The dichotomy seems to be conferred primarily by differences in distribution, density, etc. of voltage dependent sodium and potassium channel A-type, especially along the somatodendritic axis [439] CA1 neurons and subiculum neurons in hippoampus differ in firing pattern the former being regular and the later being either regular, weakly bursting or strongly bursting and resting membrane properties such as input restistance and membran time constant; however, low concentration of 4-AP 50 uM can convert neurons in both regions into firing bursting action potentials [440]. Na impulses may underly "fast prepotentials" that boost distal EPSPs [75]. Na action potentials support backpropagating impulses [57], and can activate Ca action potentials [57]. Patch recordings yield an approximate channel density of 28 pS/micron^2 in juvenile rats ] 4 wks of age, rising to 61 pS/micron^2 in older rats. Channel density was similar in other dendritic compartments [140]. [180]. Inactivation of dendritic Na channel contributes to the attenuation of activity-dependent backpropagation of APs [435]. Slow inactivation of sodium channels in dendrites and soma will modulate neuronal excitability in a way that depends in a complicated manner on the resting potential and previous history of action potential firing [436]. Dendritic can fire sodium spikes that can precede somatic action potentials APs, the probability and amplitude of which depend on previous synaptic and firing history. Some dendritic spikes could occur in the absense of somatic APs, indicating that their propagation to soma is unreliable [437]. Single action potential backpropagations show dichotomy of either strong attenuation 26-42% or weak attenuation 71-87%. The dichotomy seems to be conferred primarily by differences in distribution, density, etc. of voltage dependent sodium and potassium channel A-type, especially along the somatodendritic axis [439] Using confocal microscopy, these channels were found to be localized on the soma, dendrites, and a subpopulation of dendritic spines [402]. The way that different parts of a neuron carry out multiple information processing roles is illustrated by the CA1 pyramidal cell in the hippocampus. The authors used 2-photon microscopy to obtain high resolution images of calcium signals in the apical dendrites while activating Schaffer collateral inputs to induce long-term potentiation LTP of different durations. Short-duration LTP LTP 1 was associated with Ca increase in dendritic spines, due to activation of NMDA receptors and local ryanodine receptors RyRs. Intermediate duration LTP LTP 2 was associated with Ca increase in dendritic branches, due to activation of NMDA receptors and local IP3 receptors IP3Rs. For Ca increase in long duration LTP LTP3, see Ca channels in CA1 pyramidal cell apical dendrite. The authors conclude that "selective induction of different forms of LTP is achieved via spatial segregation of functionally distinct calcium signals"[540]. EM showed colocalization at axodendritic asymmetric synapses within the CA1 subfield of rat hippocampus. AMPA/NMDA receptor colocalization was found in non-GABAergic dendritic shafts as well as dendritic spines, suggesting that excitatory neuronal transmission in CA1 neurons may generally involve activation of both NMDA and AMPA receptor subunits at a single synapse [250]. Recordings from membrane patches of dendrites and soma reveal fast and slow responses to fast application of glutamate, mediated by AMPA amd NMDA receptors, respectively [434]. EM showed colocalization at axodendritic asymmetric synapses within the CA1 subfield of rat hippocampus. AMPA/NMDA receptor colocalization was found in non-GABAergic dendritic shafts as well as dendritic spines, suggesting that excitatory neuronal transmission in CA1 neurons may generally involve activation of both NMDA and AMPA receptor subunits at a single synapse [250]. Recordings from membrane patches of dendrites and soma reveal fast and slow responses to fast application of glutamate, mediated by AMPA amd NMDA receptors, respectively [434]. Glutamate is commonly believed to be the primary excitatory neurotransmitter in the hippocampal formation generally reviewed in Cotman et al., 1995, and in CA1 in particular [141], [142]. CA1 pyramidal neurons increase their firing recorded extracellularly in response to ionophoresed Glu within their apical dendritic fields or in the cell body layer Dudar 1974 PMID4437726. [183] Labeling for glutamic acid decarboxylase GAD, the enzyme that synthesizes GABA, is heavy in the molecular layer of CA1 [141], cited in Johnston and Amaral, 1998. Using confocal microscopy, these channels were found to be localized on the soma, dendrites, and a subpopulation of dendritic spines [402]. Depolarizing "sag" during larger hyperpolarizing voltage transients is indicative of Ih current in determinating the passive membrane properties of CA1 pyramidal neurons [432]. Membrane patches recorded in the cell-attached patch configuration from the soma and apical dendrites revealed an Ih that increased over sixfold from soma to distal dendrites. Ih demonstrated a mixed Na+-K+ conductance and was sensitive to low concentrations of external CsCl. As a result of Ih the propagation of subthreshold voltage transients is directionally specific. The elevated dendritic Ih density decreases EPSP amplitude and duration and reduces the time window over which temporal summation takes place [187]. A-current is reduced in the presence of beta-amyloid receptors[517]. Patch-clamp recordings reveal a high density of A-type K channels in the dendritic tree, which increases with distance from the soma [144]. A shift toward more depolarized potentials of the activation curve has also been observed in mid and distal dendrites more than 100um [144]. These channels "prevent initiation of an action potential in the dendrites, limit the backpropagation of action potentials into the dendrites, and reduce excitatory synaptic events" [144]. Single action potential backpropagations show dichotomy of either strong attenuation 26-42% or weak attenuation 71-87%. The dichotomy seems to be conferred primarily by differences in distribution, density, etc. of voltage dependent sodium and potassium channel A-type, especially along the somatodendritic axis [439] CA1 neurons and subiculum neurons in hippoampus differ in firing pattern the former being regular and the later being either regular, weakly bursting or strongly bursting and resting membrane properties such as input restistance and membran time constant; however, low concentration of 4-AP 50 ?M can convert neurons in both regions into firing bursting action potentials [440]. "action potential-mediated depolarization can...result in the elevation of dendritic intracellular Ca concentration Regehr et al 1989, [76], which is important for the induction of long term changes in synaptic strength" [57]. Na impulses may underly "fast prepotentials" that boost distal EPSPs [75]. Na action potentials support backpropagating impulses [57], and can activate Ca action potentials [57]. Patch recordings yield an approximate channel density of 28 pS/micron^2 in juvenile rats ] 4 wks of age, rising to 61 pS/micron^2 in older rats. Channel density was similar in other dendritic compartments [140]. [180]. Inactivation of dendritic Na channel contributes to the attenuation of activity-dependent backpropagation of APs [435]. Slow inactivation of sodium channels in dendrites and soma will modulate neuronal excitability in a way that depends in a complicated manner on the resting potential and previous history of action potential firing [436]. Single action potential backpropagations show dichotomy of either strong attenuation 26-42% or weak attenuation 71-87%. The dichotomy seems to be conferred primarily by differences in distribution, density, etc. of voltage dependent sodium and potassium channel A-type, especially along the somatodendritic axis [439] Ca fluorescence imaging shows that application of L-channel antagonists reduces the Ca influx associated with backpropagating action potentials, and has a significantly greater effect in the proximal dendrites than in more distal dendrites [143]. Patch recordings yield an approximate channel density of 7 pS/micron^2 in juvenile rats ] 4 wks of age, rising to 10 pS/micron^2 in older rats. Ca channel density was similar in other dendritic compartments, and in general lower than Na channel density [140]. However, in a few apical patches the channel density was increased X 3, which could indicate channel clustering. Ca fluorescence imaging shows that application of T-channel antagonists reduces the Ca influx associated with backpropagating action potentials, and has a two-fold greater effect in the soma than in the dendrites [143]. Recordings from membrane patches of dendrites and soma reveal fast and slow responses to fast application of glutamate, mediated by AMPA amd NMDA receptors, respectively [434]. The baskets formed by inhibitory basket cells have high concentrations of glutamic acid decarboxylase GAD, the enzyme that synthesizes GABA [141]. A 40-50% reduction in a small fraction of peri- somatic synapses with large or complex postsynaptic structure after kindling has been found. This functionally relevant reduction may be related to the loss of a specific class of interneurons, and could underlie the enhanced seizure susceptibility after kindling epileptogenesis [284]. Recordings from membrane patches of dendrites and soma reveal fast and slow responses to fast application of glutamate, mediated by AMPA amd NMDA receptors, respectively [434]. Patch recordings indicate channels similar in basic characteristics to one or more of the HVAm channel types most likely Q- or R-type channels[140]. The properties of voltage-gated potassium currents were studied in acutely isolated rat cells from area CA1 and CA3 at postnatal ages of day 6-8, 9-14, and 26-29 P6-8, P9-14, and P26-29 with the use of the whole cell version of the patch-clamp technique. In CA1 cells IK was blocked by TEA at +30 mV with an IC50 of 0.98 mM. In CA3 cells the corresponding IC50 value was 1.05 mM. About 20% of IK were insensitive to TEA. IK was partially blocked by approximately 30% with 100 microM 4-AP. Mast cell degranulating peptide 100-200 nM and dendrotoxin 50-300 nM had no effect on IK. IK was upregulated with increasing postnatal age. This increase in the expression of IK was approximately 300% much larger in CA1 cells than in CA3 cells, with only approximately 50% [162]. Cells were voltage-clamped using a single microelectrode, at 23-30 degrees C. M-current resembled that of sympathetic ganglion cells. It was abolished by addition of carbachol, muscarine or bethanechol, as well as by 1 mM barium. It was suggested that activation of cholinergic septal inputs to the hippocampus facilitates repetitive firing of pyramidal cells by turning off the M-conductance, without much change in the resting potential of the cell [197]. It was was blocked by linopirdine in a reversible, concentration-dependent manner [198], and by cholinergic agonists in slices [199]. Serotonin produced a slowly developing and long-lasting suppression of IM leading to depolarization end excitation [200]. It was decreased by cannabinoids [287]. Depolarizing "sag" during larger hyperpolarizing voltage transients is indicative of Ih current in determinating the passive membrane properties of CA1 pyramidal neurons [432]. Membrane patches recorded in the cell-attached patch configuration from the soma and apical dendrites revealed an Ih that increased over sixfold from soma to distal dendrites. Ih demonstrated a mixed Na+-K+ conductance and was sensitive to low concentrations of external CsCl. As a result of Ih the propagation of subthreshold voltage transients is directionally specific. The elevated dendritic Ih density decreases EPSP amplitude and duration and reduces the time window over which temporal summation takes place [187]. Patch recordings [140]. Using confocal microscopy, these channels were found to be localized on the soma, dendrites, and a subpopulation of dendritic spines [402]. Membrane patches recorded in the cell-attached patch configuration from the soma and apical dendrites revealed an Ih that increased over sixfold from soma to distal dendrites. Ih demonstrated a mixed Na+-K+ conductance and was sensitive to low concentrations of external CsCl. As a result of Ih the propagation of subthreshold voltage transients is directionally specific. The elevated dendritic Ih density decreases EPSP amplitude and duration and reduces the time window over which temporal summation takes place [187]. Patch-clamp recordings reveal A-type K channels in the soma[144]. T-type channels are less dense in the soma than in the dendrites [140]. Patch recordings yield an approximate channel density of 45 pS/micron^2 compared with 28 pS/micron^2 in dendrites in juvenile rats ] 4 wks of age, rising modestly to 56 pS/micron^2 compared with 61 pS/micron^2 in dendrites in older rats [140]. [180]. Recordings using the intracellular perfusion method showed no differences between the I-V characteristics of CA1 and CA3 neurones for this current. In contrast to this, the steady-state inactivation of both types of neurones was significantly different [292]. Inactivation of dendritic Na channel contributes to the attenuation of activity-dependent backpropagation of APs [435]. Slow inactivation of sodium channels in dendrites and soma will modulate neuronal excitability in a way that depends in a complicated manner on the resting potential and previous history of action potential firing [436]. In patch recordings, "HVA-l channels reminiscent of L-type channels were occasionally encountered primarily in the more proximal dendrites" and in the soma [140]. A single-electrode voltage-clamp technique was employed on slices to examine slow AHP. This was achieved by using conventional procedures to evoke an AHP in current clamp, followed rapidly by a switch into voltage clamp hybrid clamp. The AHP current showed a dependence on extracellular K+ close to that predicted by the Nernst equation. It could be blocked by Cd2+ or norepinephrine, showed a requirement for voltage-dependent Ca2+ entry, but did not show any clear intrinsic voltage dependence. Once activated, AHP current is not turned off by hyperpolarizing the membrane potential [191]. Cell-attached patches on the proximal 100um of the apical dendrite did not contain sAHP channels. Amputation of the apical dendrite approximately 30 micron from the soma, while simultaneously recording the sAHP whole cell current at the soma, depressed the sAHP amplitude by only approximately 30% compared with control. Somatic cell-attached and nucleated patches did not contain sAHP current. Amputation of the axon about 20um from the soma had little effect on the amplitude of the sAHP. By this process of elimination, it is suggested that sAHP channels may be concentrated in the basal dendrites of CA1 pyramids [192]. In situ hybridization of three cloned SK channel subunits SK1-3, the prime candidates likely to underlie Ca2+-dependent AHPs showed high levels of expression in regions presenting prominent AHP currents including CA1-3 regions of the hippocampus SK1 and SK2, reticularis thalami SK1 and SK2, supraoptic nucleus SK3, and inferior olivary nucleus SK2 and SK3 [193]. The role of large-conductance Ca2+-dependent K+ channels BK in spike broadening during repetitive firing was studied using sharp electrode and computer modelling. The amplitude of the fast after-hyperpolarization fAHP rapidly declined during each train. Suppression of BK-channel activity with the selective BK-channel blocker iberiotoxin, the non-peptidergic BK-channel blocker paxilline, or calcium-free medium, broadened the 1st spike to a similar degree approximately 60 % [194]. p2 The way that different parts of a neuron carry out multiple information processing roles is illustrated by the CA1 pyramidal cell in the hippocampus. The authors used 2-photon microscopy to obtain high resolution images of calcium signals in the apical dendrites while activating Schaffer collateral inputs to induce long-term potentiation LTP of different durations. Short-duration LTP LTP 1 was associated with Ca increase in dendritic spines, due to activation of NMDA receptors and local ryanodine receptors RyRs. Intermediate duration LTP LTP 2 was associated with Ca increase in dendritic branches, due to activation of NMDA receptors and local IP3 receptors IP3Rs. For Ca increase in long duration LTP LTP3, see Ca channels in CA1 pyramidal cell apical dendrite. The authors conclude that "selective induction of different forms of LTP is achieved via spatial segregation of functionally distinct calcium signals"[540]. EM showed colocalization at axodendritic asymmetric synapses within the CA1 subfield of rat hippocampus. AMPA/NMDA receptor colocalization was found in non-GABAergic dendritic shafts as well as dendritic spines, suggesting that excitatory neuronal transmission in CA1 neurons may generally involve activation of both NMDA and AMPA receptor subunits at a single synapse [250]. EM showed colocalization at axodendritic asymmetric synapses within the CA1 subfield of rat hippocampus. AMPA/NMDA receptor colocalization was found in non-GABAergic dendritic shafts as well as dendritic spines, suggesting that excitatory neuronal transmission in CA1 neurons may generally involve activation of both NMDA and AMPA receptor subunits at a single synapse [250]. --- GABAA-mediated bicuculline-sensitive inhibitory responses can be demonstrated in CA1 neurons by extracellular recording Curtis et al, 1970 and by recording spontaneous synaptic currents Collingridge, 1984. [183] The baskets formed by inhibitory basket cells have high concentrations of glutamic acid decarboxylase GAD, the enzyme that synthesizes GABA [141]. Extracelluar ACPD an mGluR agonist application to apical or basal dendrites of CA1 pyramidal neurons causes local increases in calcium concentration that propagate throughout the cell, as measured by simultaneous whole cell recording and confocal microscopy with calcium imaging [146], suggesting the presence of mGluRs. [148] provide evidence that activation of these receptors is necessary for LTP induction Membrane patches recorded in the cell-attached patch configuration from the soma and apical dendrites revealed an Ih that increased over sixfold from soma to distal dendrites. Ih demonstrated a mixed Na+-K+ conductance and was sensitive to low concentrations of external CsCl. As a result of Ih the propagation of subthreshold voltage transients is directionally specific. The elevated dendritic Ih density decreases EPSP amplitude and duration and reduces the time window over which temporal summation takes place [187]. A-current is reduced in the presence of beta-amyloid receptors[517]. Patch-clamp recordings reveal a high density of A-type K channels in the dendritic tree, which increases with distance from the soma [144]. These channels "prevent initiation of an action potential in the dendrites, limit the backpropagation of action potentials into the dendrites, and reduce excitatory synaptic events" [144]. Single action potential backpropagations show dichotomy of either strong attenuation 26-42% or weak attenuation 71-87%. The dichotomy seems to be conferred primarily by differences in distribution, density, etc. of voltage dependent sodium and potassium channel A-type, especially along the somatodendritic axis [439] CA1 neurons and subiculum neurons in hippoampus differ in firing pattern the former being regular and the later being either regular, weakly bursting or strongly bursting and resting membrane properties such as input restistance and membran time constant; however, low concentration of 4-AP 50 uM can convert neurons in both regions into firing bursting action potentials [440]. A D-type potassium current is involved in dendritic calcium spikes initiation and repolarization [438]. CA1 neurons and subiculum neurons in hippoampus differ in firing pattern the former being regular and the later being either regular, weakly bursting or strongly bursting and resting membrane properties such as input restistance and membran time constant; however, low concentration of 4-AP 50 181M can convert neurons in both regions into firing bursting action potentials [440]. Na impulses may underly "fast prepotentials" that boost distal EPSPs [75]. Na action potentials support backpropagating impulses [57], and can activate Ca action potentials [57]. Patch recordings yield an approximate channel density of 28 pS/micron^2 in juvenile rats ] 4 wks of age, rising to 61 pS/micron^2 in older rats. Channel density was similar in other dendritic compartments [140]. However, channel density varied widely in the proximal compartment, possibly indicating the presence of hot spots. [180]. Inactivation of dendritic Na channel contributes to the attenuation of activity-dependent backpropagation of APs [435]. Slow inactivation of sodium channels in dendrites and soma will modulate neuronal excitability in a way that depends in a complicated manner on the resting potential and previous history of action potential firing [436]. Single action potential backpropagations show dichotomy of either strong attenuation 26-42% or weak attenuation 71-87%. The dichotomy seems to be conferred primarily by differences in distribution, density, etc. of voltage dependent sodium and potassium channel A-type, especially along the somatodendritic axis [439] Patch recordings yield an approximate channel density of 7 pS/micron^2 in juvenile rats ] 4 wks of age, rising to 10 pS/micron^2 in older rats. Ca channel density was similar in other dendritic compartments, and in general lower than Na channel density [140]. However, in a few apical patches the channel density was increased X 3, which could indicate channel clustering. Ca fluorescence imaging shows that application of T-channel antagonists reduces the Ca influx associated with backpropagating action potentials, and has a two-fold greater effect in the dendrites than in the soma [141]. Ca fluorescence imaging shows that application of P-channel antagonists reduces the Ca influx associated with backpropagating action potentials [141]. "action potential-mediated depolarization can...result in the elevation of dendritic intracellular Ca concentration Regehr et al 1989, [76], which is important for the induction of long term changes in synaptic strength" [57]. Using a monoclonal antibody [196] showed that the proximal dendrites and somata of hippocampal neurons label for L-type Ca2+ channels and that these channels tend to cluster near the bases of the neural processes. In patch recordings, "HVA-l channels reminiscent of L-type channels were occasionally encountered primarily in the more proximal dendrites" and in the soma [140]. Ca fluorescence imaging shows that application of L-channel antagonists reduces the Ca influx associated with backpropagating action potentials, and has a significantly greater effect in the proximal dendrites than in more distal dendrites [143]. Whole-cell somatic recording during TTX application to proximal dendrites suggests the presence of a persistent Na current [148]. Ca fluorescence imaging shows that application of N-channel antagonists slightly reduces the Ca influx associated with backpropagating action potentials [143]. Using confocal microscopy, these channels were found to be localized on the soma, dendrites, and a subpopulation of dendritic spines [402]. Experimental findings support a cascade for induction of homosynaptic, NO-dependent LTD involving activation of guanylyl cyclase, production of guanosine 3',5' cyclic monophosphate and subsequent PKG activation. This process has an additional requirement for release of Ca2+ from ryanodine-sensitive stores [263]. Extracellular recordings in vivo suggested that the dendritic density of these channels rapidly decreases with distance from soma [399]. Bath application of Pb2+ shifted the neurons curent-voltage relation in patch-clamp recording from acutely isolated pyramidal neurons. These results were interpreted to "demonstrate that Pb2+ in micromolar concentration is a voltage-dependent, reversible blocker of delayed-rectifier potassium currents of hippocampal neurons" [164]. In a study of acutely isolated rat cells under whole cell recording across development states Day 6 - Day 29, it was found that delayed rectifier currents decayed along a double-exponential time course and were 50% blocked by TEA tetraethylammonium, a KDR antagonist at +30 mV at a concentration of about 1mM, as well as being partially blocked by 4-AP 4-aminopyridine. The current also appeared to increase over this development period. This increase was approximately 300% much larger in CA1 cells than in CA3 cells, with only approximately 50% [162]. A combined in situ hybridization and immunocytochemical study demonstrated that Kv1.2 which probably corresponds to IK channels is concentrated in the dendrites of CA3 neurons [173]. Experimental findings support a cascade for induction of homosynaptic, NO-dependent LTD involving activation of guanylyl cyclase, production of guanosine 3',5' cyclic monophosphate and subsequent PKG activation. This process has an additional requirement for release of Ca2+ from ryanodine-sensitive stores [263]. Quantitative autoradiography has been used to localize [3H]AMPA binding sites. It was found that AMPARs are found in a high concentration in the hippocampus relative to other areas in the brain. In CA3, labeling was substantially heavier in s. pyramidale than in s.radiatum and s. lacunosum-moleculare [170]. The physiology of these receptors has been studied in outside-out patches from the proximal apical dendrites. It was found that a CNQX-sensitive component of the synaptic current evoked by fast aplication of glutamate could be isolated and was presumed to be the result of AMPA channel opening. It was calculated that AMPA channels had a mean elementary conductance of 10 pS estimated by non-stationary fluctuation analysis and was found that the channels had a low permeability to Ca2+. The reversal potential for AMPA receptors was found to be about 0 mV with an almost linear peak current-voltage relationship [174]; see also [159]. It has also been found that CNQX does not block the intracellular calcium concentration increase normally associated with stratum lucidum stimulation [168]. Recordings from membrane patches of dendrites and soma reveal fast and slow responses to fast application of glutamate, mediated by AMPA amd NMDA receptors, respectively [434]. Quantitative autoradiography has been used to localize sites at which L-[3H]-glutamate is displaced by NMDA. The labelling of these receptors was somewhat lower than in CA1 overall, being highest in s. oriens and s. radiatum and very low in s.pyramidale and s. lucidum [169]. In contrast, a study using radioactive in situ hybridization histochemistry looked at mRNA coding an NMDA glutamate binding protein and at NMDAR1 an NMDAR subunit expression and found heavy labeling for both in the pyramidal and polymorphic layers but little in the molecular layer [172].The physiology of these receptors has been studied in outside-out patches from the proximal apical dendrites. It was found that an APV-sensitive component of the synaptic current evoked by fast aplication of glutamate could be isolated and was presumed to be the result of NMDA channel opening. It was calculated that NMDA channels had a main conductance state conductance of 45 pS and it was confirmed that the channel was permeable to Ca2+. The NMDAR-mediated conductance was blocked by Mg2+ in a voltage-dependent way and by Zn2+ in a non-voltage-dependent fashion [174]; see also [159]. NMDA iontophoretically applied to basal dendrites evoked inward currents near resting potential. Changing levels of bath calcium concentration downwards by 50% caused an increase in the inward current [155]. MK801 an NMDAR antagonist blocks the transient intracellular Ca2+ release normally associated with stratum lucidum stimulation found by simultaneous Ca imaging and intracellular recording in rat brain slices by [168]. While NMDA receptor activation may be necessary for LTP at the commissural/associational synapses [156], it has been shown to occur at mossy fiber synapses even in the presence of NMDA receptor antagonists under certain conditions [156]; [157] Differential induction of potentiation and depression at commissural and mossy fiber synapses has also been shown by R158E. Recordings from membrane patches of dendrites and soma reveal fast and slow responses to fast application of glutamate, mediated by AMPA amd NMDA receptors, respectively [434]. Bath application of Pb2+ shifted the neurons curent-voltage relation in patch-clamp recording from acutely isolated pyramidal neurons. These results were interpreted to "demonstrate that Pb2+ in micromolar concentration is a voltage-dependent, reversible blocker of delayed-rectifier potassium currents of hippocampal neurons" [164]. In a study of acutely isolated rat cells under whole cell recording across development states Day 6 - Day 29, it was found that delayed rectifier currents decayed along a double-exponential time course and were 50% blocked by TEA tetraethylammonium, a IK antagonist at +30 mV at a concentration of about 1mM, as well as being partially blocked by 4-AP 4-aminopyridine. The current also appeared to increase over this development period. This increase was approximately 300% much larger in CA1 cells than in CA3 cells, with only approximately 50% [162]. A combined in situ hybridization and immunocytochemical study demonstrated that Kv1.2 which may correspond to IK channels is concentrated in the dendrites of CA3 neurons [173]. Intracellular recording from CA3 pyramidal neurons in a slice culture from rat found a slow excitatory response to Glu application in the presence of blocking agents for the ionotropic GluRs. Further experimentation revealed that ACPD could evoke the same response, which was due to the depression of IK, Ca and voltage-gated IK [151]. A subsequent study in rat slice cultures has shown that bath application of MCPG a mGluR antagonist blocks the inward Ca-dependent K-current associated with ACPD application or mossy fiber stimulation in the presence on ionotropic GluR antagonists [155]. Another study using bath application of 1S,3R-ACPD in rat slice cultures during single electrode voltage clamp recording showed that depolarizing current steps revealed a suppression of K currents leading to a negative slope conductance at potential between -55mV and -40 mV [163]. mGluR2 knockout mice show normal LTP and synaptic transmission but not LTD [175]. It has also been shown using whole and perforated patch recording from acutely isolated CA3 pyramidal neurons that application of Glu and quisqualatic acid in the presence of D-AP5, an NMDAR-antagonist, and CNQX, an AMPAR antagonist results in responses that consist of an inward current that may be preceded by an outward current. Both of these currents are affected by bath [K] and they had different pharmacological properties Harata et al, 1996. Hilar stimulation has been used to elicit pharmacologically isolated IPSPs in CA3 pyramidal neurons recorded by means of intracellular or whole cell methods depending on the age of the animal. Paired pulse stimulation in this preparation resulted in paired pulse depression, which could be reduced by bath application of CGP35348 a GABABR antagonist in adult rats. Neonatal rats 5-7 days old showed paired pulse depression only within a much shorter range of interstimulus intervals and it was not affected by CGP35348 unless transmitter release was facilitated by raising the bath [Ca2+] and lowering the bath [Mg+] [150]. Quantitative autoradiography has been used to localize [3H]AMPA binding sites. It was found that AMPARs are found in a high concentration in the hippocampus relative to other areas in the brain. In CA3, labeling was substantially heavier in s. pyramidale than in s.radiatum and s. lacunosum-moleculare [170]. The physiology of these receptors has been studied in outside-out patches from the proximal apical dendrites. It was found that a CNQX-sensitive component of the synaptic current evoked by fast aplication of glutamate could be isolated and was presumed to be the result of AMPA channel opening. It was calculated that AMPA channels had a mean elementary conductance of 10 pS estimated by non-stationary fluctuation analysis and was found that the channels had a low permeability to Ca2+. The reversal potential for AMPA receptors was found to be about 0 mV with an almost linear peak current-voltage relationship [174]; see also [159]. It has also been found that CNQX does not block the intracellular calcium concentration increase normally associated with stratum lucidum stimulation [173]. A study using simultaneous intracellular recording from interneurons and pyramidal neurons combined with biocytin cell fills and morphological reconstructions revealed that the interneurons made connections onto the soma and proximal dendrites of the pyramidal neuron and that stimulation of the interneurons evoked IPSPs in the pyramidal neurons. EM microscopy revealed differential numbers of terminals depending on the subcellular locus of the connections. [167]. Quantitative autoradiography has been used to localize sites at which L-[3H]-glutamate is displaced by NMDA. The labelling of these receptors was somewhat lower than in CA1 overall, being highest in s. oriens and s. radiatum and very low in s.pyramidale and s. lucidum [169]. In contrast, a study using radioactive in situ hybridization histochemistry looked at mRNA coding an NMDA glutamate binding protein and at NMDAR1 an NMDAR subunit expression and found heavy labeling for both in the pyramidal and polymorphic layers but little in the molecular layer [172]. The physiology of these receptors has been studied in outside-out patches from the proximal apical dendrites. It was found that an APV-sensitive component of the synaptic current evoked by fast aplication of glutamate could be isolated and was presumed to be the result of NMDA channel opening. It was calculated that NMDA channels had a main conductance state conductance of 45 pS and it was confirmed that the channel was permeable to Ca2+. The NMDAR-mediated conductance was blocked by Mg2+ in a voltage-dependent way and by Zn2+ in a non-voltage-dependent fashion [174]; see also [159]. NMDA iontophoretically applied to basal dendrites evoked inward currents near resting potential. Changing levels of bath calcium concentration downwards by 50% caused an increase in the inward current [155]. MK801 an NMDAR antagonist blocks the transient intracellular Ca2+ release normally associated with stratum lucidum stimulation found by simultaneous Ca imaging and intracellular recording in rat brain slices by [168]. While NMDA receptor activation may be necessary for LTP at the commissural/associational synapses [156], it has been shown to occur at mossy fiber synapses even in the presence of NMDA receptor antagonists under certain conditions [156]; [157] Differential induction of potentiation and depression at commissural and mossy fiber synapses has also been shown by [152]. Intracellular recording from organotypic rat hippocampal cultures have shown that approximately 25% of single spikes in CA3 pyramidal neurons are followed by IPSPs at a fixed latency, presumeably a result of feedback inhibition from inhibitory interneurons. The addition of bicuculline a competitive GABAA antagonist completely abolished these responses, but they were insensitive to CGP35348, a GABAB antagonist [154]. There is also evidence that Zn+ can modulate bicuculline-sensitive responses to GABA [165] early in development in rat studied ]8 days old.