NMDA and AMPA receptors contribute similarly to temporal processing in mammalian retinal ganglion cells

Abstract

Key pointsr In most areas of the brain, NMDA-type glutamate receptors (NMDARs) exhibit slower kinetics than do AMPA-type receptors (AMPARs).r Most retinal ganglion cells express a combination of AMPARs and NMDARs, but whether NMDAR kinetics limit temporal encoding of light stimulation is not well understood.r In this study, we measured AMPAR-and NMDAR-mediated conductances evoked by visual stimulation in two types of guinea pig retinal ganglion cell.r In both cell types, AMPAR-and NMDAR-mediated responses encoded rapidly varying contrast modulation within the physiological range (up to 18 temporal cycles s -1 ).r In retinal ganglion cells, NMDARs and AMPARs act together to encode a wide range of temporal frequencies, suggesting that NMDARs in some sensory neurons have relatively fast kinetics.Abstract Postsynaptic AMPA-and NMDA-type glutamate receptors (AMPARs, NMDARs) are commonly expressed at the same synapses. AMPARs are thought to mediate the majority of fast excitatory neurotransmission whereas NMDARs, with their relatively slower kinetics and higher Ca 2+ permeability, are thought to mediate synaptic plasticity, especially in neural circuits devoted to learning and memory. In sensory neurons, however, the roles of AMPARs and NMDARs are less well understood. Here, we tested in the in vitro guinea pig retina whether AMPARs and NMDARs differentially support temporal contrast encoding by two ganglion cell types. In both OFF Alpha and Delta ganglion cells, contrast stimulation evoked an NMDAR-mediated response with a characteristic J-shaped I-V relationship. In OFF Delta cells, AMPAR-and NMDAR-mediated responses could be modulated at low frequencies but were suppressed during 10 Hz stimulation, when responses were instead shaped by synaptic inhibition. With inhibition blocked, both AMPAR-and NMDAR-mediated responses could be modulated at 10 Hz, indicating that NMDAR kinetics do not limit temporal encoding. In OFF Alpha cells, NMDAR-mediated responses followed stimuli at frequencies up to ß18 Hz. In both cell types, NMDAR-mediated responses to contrast modulation at 9-18 Hz showed delays of <10 ms relative to AMPAR-mediated responses. Thus, NMDARs combine with AMPARs to encode rapidly modulated glutamate release, and NMDAR kinetics do not limit temporal coding by OFF Alpha and Delta ganglion cells substantially. Furthermore, glutamatergic transmission is differentially regulated across bipolar cell pathways: in some, release is suppressed at high temporal frequencies by presynaptic inhibition.

Directional excitatory input to direction‐selective ganglion cells in the rabbit retina

“…Moreover, NMDAR mediated excitatory inputs have been observed in rabbit DSGCs (Lee et al, ). In other ganglion cell types recorded under identical or very similar recording conditions, nonlinearity in the I‐V relations due to NMDARs could be observed, and showed sensitivity to NMDAR antagonists (Lee et al, ; Stafford, Manookin, Singer, & Demb, ; Venkataramani & Taylor, ). In the current experiments, the I‐V relations did not display a strong NMDAR nonlinearity, even after acetylcholine receptors were blocked (Figure c), suggesting that any NMDAR mediated component is relatively minor.…”

A Central Role for Mixed Acetylcholine/GABA Transmission in Direction Coding in the Retina

“…Most strikingly, AMPAR-mediated synaptic activity in DSGCs is absent at low contrast and only emerges at the higher-contrast levels. This is unusual, as in most ganglion cells the AMPAR conductance is the dominant excitatory conductance (Diamond and Copenhagen, 1993;Sagdullaev et al, 2006;Sethuramanujam and Slaughter, 2015;Zhang and Diamond, 2009), and AMPARs and NMDARs are usually activated in parallel when contrast (Buldyrev et al, 2012;Diamond and Copenhagen, 1995;Manookin et al, 2010) or temporal frequency (Stafford et al, 2014) is varied. Whether different types of bipolar cells differentially use NMDARs and AMPARs, or whether these receptors are expressed at the same synapses and the system relies on the distinct affinities of these receptors (Patneau and Mayer, 1990) to signal different levels of glutamate release evoked by varying contrasts remains to be investigated.…”

Functional Circuitry of the Retina

“…Some ganglion cell types use NMDA receptors for the primary depolarizing response, whereas others have minimal NMDA receptor activity under physiological conditions (i.e., light-evoked responses with intact inhibition) (Manookin et al 2010, Venkataramani & Taylor 2010, Buldyrev et al 2012, Crook et al 2014). Both receptor types can respond to rapidly modulated presynaptic glutamate release (Stafford et al 2014). Beyond encoding light-evoked glutamate release, NMDA receptors could play a role in regulating the density and subtype of synaptic AMPA receptors ( Jones et al 2012).…”