155. Gerber U, Lüthi A and Gähwiler BH. (1993) Inhibition of a slow synaptic response by a metabotropic glutamate receptor antagonist in hippocampal CA3 pyramidal cells. Proc Biol Sci 254:169-72 [Journal] .

NeuronCompartmentPropertyConnectivityNotes
Hippocampus CA3 pyramidal cellDistal apical dendriteNMDAPerforant pathway entorhinal pyramidal neuron terminals (T)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 (Monaghan DT and Cotman CW, 1985169 ). 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 (Sato K et al, 1995 [rat ]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 (Spruston N et al, 1995 [rat ]174 ; see also Jahr CE and Stevens CF, 2000 [rat ]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 (Gerber U et al, 1993 [rat ]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 Pozzo Miller LD et al, 1996168 ). While NMDA receptor activation may be necessary for LTP at the commissural/associational synapses (Gorter JA and Brady RJ, 1995 [rat ]156 ), it has been shown to occur at mossy fiber synapses even in the presence of NMDA receptor antagonists under certain conditions (Gorter JA and Brady RJ, 1995 [rat ]156 ; Harris EW and Cotman CW, 1986157 ) Differential induction of potentiation and depression at commissural and mossy fiber synapses has also been shown by #R#158#E#. 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 (Spruston N et al, 1995434 ).
Hippocampus CA3 pyramidal cellMiddle apical dendriteNMDACA3 Pyramidal neuron terminals (T)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 (Monaghan DT and Cotman CW, 1985169 ). 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 (Sato K et al, 1995 [rat ]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 (Spruston N et al, 1995 [rat ]174 ; see also Jahr CE and Stevens CF, 2000 [rat ]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 (Gerber U et al, 1993 [rat ]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 Pozzo Miller LD et al, 1996168 ). While NMDA receptor activation may be necessary for LTP at the commissural/associational synapses (Gorter JA and Brady RJ, 1995 [rat ]156 ), it has been shown to occur at mossy fiber synapses even in the presence of NMDA receptor antagonists under certain conditions (Gorter JA and Brady RJ, 1995 [rat ]156 ; Harris EW and Cotman CW, 1986157 ) Differential induction of potentiation and depression at commissural and mossy fiber synapses has also been shown by Chattarji S et al, 1989152 .
Hippocampus CA3 pyramidal cellMiddle apical dendritemGluRReceptor Notes Dentate Granule Cell mossy terminals (T) 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 I(K, Ca) and voltage-gated I(K) (Charpak S et al, 1990151 ). 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 (Gerber U et al, 1993 [rat ]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 (Lüthi A et al, 1997163 ). mGluR2 knockout mice show normal LTP and synaptic transmission but not LTD (Yokoi M et al, 1996 [mice ]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).
Hippocampus CA3 pyramidal cellSomamGluR-----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 I(K,Ca) and voltage-gated I(K) (Charpak S et al, 1990151 ). 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 (Gerber U et al, 1993 [rat ]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 (Lüthi A et al, 1997163 ). mGluR2 knockout mice show normal LTP and synaptic transmission but not LTD (Yokoi M et al, 1996 [mice ]175 ). It has also been shown (using whole cell 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 #8680866).

References
169. Monaghan DT and Cotman CW. (1985) Distribution of N-methyl-D-aspartate-sensitive L-[3H]glutamate-binding sites in rat brain. J Neurosci 5:2909-19.
172. Sato K, Mick G, Kiyama H and Tohyama M. (1995) Expression patterns of a glutamate-binding protein in the rat central nervous system: comparison with N-methyl-D-aspartate receptor subunit 1 in rat. Neuroscience 64:459-75.
174. Spruston N, Schiller Y, Stuart G and Sakmann B. (1995) Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science 268:297-300.
159. Jahr CE and Stevens CF. (2000) Glutamate activates multiple single channel conductances in hippocampal neurons. Nature 325:522-5.
155. Gerber U, Lüthi A and Gähwiler BH. (1993) Inhibition of a slow synaptic response by a metabotropic glutamate receptor antagonist in hippocampal CA3 pyramidal cells. Proc Biol Sci 254:169-72 [Journal] .
168. Pozzo Miller LD, Petrozzino JJ, Golarai G and Connor JA. (1996) Ca2+ release from intracellular stores induced by afferent stimulation of CA3 pyramidal neurons in hippocampal slices. J Neurophysiol 76:554-62.
156. Gorter JA and Brady RJ. (1995) Modulation of N-methyl-D-aspartic acid receptors by extracellular calcium in immature and adult hippocampal slices: whole cell recordings in CA3 pyramidal cells. Neurosci Lett 194:209-13.
157. Harris EW and Cotman CW. (1986) Long-term potentiation of guinea pig mossy fiber responses is not blocked by N-methyl D-aspartate antagonists. Neurosci Lett 70:132-7.
434. Spruston N, Jonas P and Sakmann B. (1995) Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons. J Physiol 482 ( Pt 2):325-52.
152. Chattarji S, Stanton PK and Sejnowski TJ. (1989) Commissural synapses, but not mossy fiber synapses, in hippocampal field CA3 exhibit associative long-term potentiation and depression. Brain Res 495:145-50.
151. Charpak S, Gahwiler BH, Do KQ and Knopfel T. (1990) Potassium conductances in hippocampal neurons blocked by excitatory amino-acid transmitters. Nature 347:765-7.
163. Lüthi A, Gähwiler BH and Gerber U. (1997) 1S, 3R-ACPD induces a region of negative slope conductance in the steady-state current-voltage relationship of hippocampal pyramidal cells. J Neurophysiol 77:221-8.
175. Yokoi M, Kobayashi K, Manabe T, Takahashi T, Sakaguchi I, Katsuura G, Shigemoto R, Ohishi H, Nomura S, Nakamura K, Nakao K, Katsuki M and Nakanishi S. (1996) Impairment of hippocampal mossy fiber LTD in mice lacking mGluR2. Science 273:645-7.
_1/16/2018 12:07:45 PM