Excitatory Synaptic Transmission in the Inner Retina: Paired Recordings of Bipolar Cells and Neurons of the Ganglion Cell Layer

Abstract

Properties of glutamatergic synaptic transmission were investigated by simultaneously voltage-clamping a pair of connected bipolar cells and cells in the ganglion cell layer (GLCs) in the newt retinal slice preparation. Activation of the Ca2+ current in a single bipolar cell was essential for evoking the glutamatergic postsynaptic current in the GLC. Depolarization for as short as 15 msec activated both NMDA and non-NMDA receptors. On the other hand, analysis of the spontaneous glutamatergic synaptic currents of GLCs revealed that these currents consisted of mainly non-NMDA receptor activation with little contribution from NMDA receptors. This suggests that non-NMDA receptors of GLCs are clustered in postsynaptic membrane regions immediately beneath the release sites of bipolar cells and that NMDA receptors have lower accessibility to the released transmitter than non-NMDA receptors. Glutamate that is spilled over from the release sites may activate the NMDA receptors. When a prolonged depolarizing pulse was applied to a bipolar cell, the response induced by non-NMDA receptors was limited greatly by their fast desensitization, whereas NMDA receptors were able to produce a maintained response. The relationship between the pulse duration applied to the bipolar cell and the integrated charge of the response evoked in the GLC was almost linear. Therefore, we propose that both non-NMDA and NMDA receptors cooperate to transfer the graded photoresponses of bipolar cells proportionally to GLCs.

Distinct perisynaptic and synaptic localization of NMDA and AMPA receptors on ganglion cells in rat retina

“…NMDARs are not activated by glutamate released from a single vesicle (Taylor et al, 1995;Matsui et al, 1998;Chen and Diamond, 2002), unless glutamate uptake is reduced (Chen and Diamond, 2002), and NMDARs encounter a lower synaptic glutamate concentration during evoked responses than do AMPARs (Chen and Diamond, 2002). Taken together, these previous physiological data and the morphological results presented here suggest that transmitter released from a single vesicle is not sufficient to activate NMDARs located perisynaptically, several hundred nm from the release site.…”

“…Although evoked EPSCs in RGCs are mediated by AMPARs and NMDARs (Mittman et al, 1990;Diamond and Copenhagen, 1993;Lukasiewicz et al, 1997;Matsui et al, 1998;Higgs and Lukasiewicz, 1999;Matsui et al, 1999;Chen and Diamond, 2002), spontaneous mEPSCs on RGCs are mediated solely by AMPARs both in mammalian and amphibian retina (rat: Chen and Diamond, 2002;salamander: Taylor et al, 1995;newt: Matsui et al, 1998). NMDARs encounter a lower glutamate concentration during evoked EPSCs than do NMDARs and an NMDAR component emerges in mEPSCs when glutamate uptake is reduced (Chen and Diamond, 2002), suggesting that NMDARs may be located extrasynaptically on RGC dendrites (see also Matsui et al, 1998). This is in apparent contrast to pre-embedding EM studies in mammalian retina indicating that NMDAR subunits are present in postsynaptic elements at cone bipolar cell ribbon synapses (Hartveit et al, 1994;Fletcher et al, 2000;Pourcho et al, 2001).…”

Active Roles of Electrically Coupled Bipolar Cell Network in the Adult Retina

“…However, asynchronous release from the Mb1-BC was evident only after the termination of a long (ϳ200 ms) depolarization (von Gersdorff et al, 1998), and thus, it seems unlikely that the brief depolarization (20 ms) could exhibit asynchronous release strong enough to evoke the long-lasting EPSC. Delayed activation of NMDA receptors in GCs (Matsui et al, 1998;Vigh and von Gersdorff, 2005) would also contribute to the longlasting EPSC. However, it seems unlikely because NMDA receptors could be mostly blocked by extracellular Mg 2ϩ at the holding potential of Ϫ60 mV (Nowak et al, 1984), and that application of D-AP5 did not change the duration of the longlasting EPSC (data not shown).…”

Mechanisms Underlying Signal Filtering at a Multisynapse Contact

“…10D, fourth row). These results suggest that NMDARs acted to compensate for the loss of AMPAR activation resulting from desensitization (Matsui et al, 1998). However, postsynaptic spike timing was no longer time locked to the presynaptic stimulation by the end of the train (Fig.…”