Postsynaptic Plasticity Triggered by Ca2+-Permeable AMPA Receptor Activation in Retinal Amacrine Cells

Abstract

SUMMARY Amacrine cells are thought to be a major locus for mechanisms of light adaptation and contrast enhancement in the retina. However, the potential for plasticity in their AMPA receptor currents remains largely unknown. Using paired patch-clamp recordings between bipolar cell terminals and amacrine cells, we have simultaneously measured presynaptic membrane capacitance changes and EPSCs. Repetitive bipolar cell depolarizations, designed to maintain the same amount of exocytosis, nevertheless significantly potentiated evoked EPSCs in a subpopulation of amacrine cells. Likewise, repetitive iontophoresis (or puffs) of glutamate (or AMPA) onto the dendrites of amacrine cells also significantly potentiated evoked currents and [Ca2+]i rises. However, strong postsynaptic Ca2+ buffering with BAPTA abolished the potentiation and selective antagonists of Ca2+-permeable AMPA receptors also blocked the potentiation of AMPA-mediated currents. Together these results suggest that Ca2+ influx via Ca2+-permeable AMPA receptors can elicit a rapid form of postsynaptic plasticity in a subgroup of amacrine cell dendrites.

Synaptic Transfer between Rod and Cone Pathways Mediated by AII Amacrine Cells in the Mouse Retina

“…To test this, we activated all OFF CBCs with kainic acid (KA, 1 mM), an exogenous AMPA/kainate receptor agonist, applied via puffer pipette [29, 30]. KA elicited inward currents in CBC2s when puffed in the OPL (Figure 3E,H) and activated glutamate receptors directly on AIIs when puffed into the OFF layer of the IPL (Figure 3F,H) [31]. KA did not, however, evoke strong synaptic responses in AIIs when puffed in the OPL (Figure 3I-K), suggesting that AIIs receive little synaptic input from any OFF CBCs.…”

“…For example, although CBC2s make numerous synaptic inputs onto AIIs (Figure 2) and OFF CBCs provide robust synaptic input to AIIs in rat retina [11], our recordings in mouse indicate functionally weak OFF CBC→ AII connectivity (Figure 3; [53]). Functional glutamate receptors clearly populate AII OFF layer lobules (Figure 3F,H; [31]), but perhaps they do not appose CBC ribbons. Electron microscopy and immunogold labeling are required to address this possibility.…”

Presynaptic Diversity Revealed by Ca2+-Permeable AMPA Receptors at the Calyx of Held Synapse

“…The majority of GluA2 subunits are edited in the brains of rodents and humans (Hume et al, 1991;Carlson et al, 2000) and animals deficient in the Q/R site editing die prematurely (Brusa et al, 1995). In several brain regions, CP-AMPARs serve important functions in the induction and modulation of activity-dependent synaptic plasticity at developing and mature synapses (Jia et al, 1996;Plant et al, 2006;Kim and von Gersdorff, 2016;Park et al, 2016). Additionally, Ca 2ϩ permeability through this receptor regulates neuronal Ca 2ϩ -induced excitotoxicity (Carriedo et al, 1998;Noh et al, 2005;Sebe et al, 2017) and the progression of several CNS pathologies are dependent on Ca 2ϩ influx through these receptors (Weiss, 2011).…”

Quantifying the effect of light activated outer and inner retinal inhibitory pathways on glutamate release from mixed bipolar cells.

“…Taken together, NBQX in the presence of PTX was expected to hyperpolarize HCs (Krizaj, Akopian, & Witkovsky, ; Verweij et al, ) and thus remove HC‐mediated inhibition in the outer retina (Davenport, Detwiler, & Dacey, ; Fahrenfort et al, ; Hirasawa & Kaneko, ; Tatsukawa et al, ; Thoreson et al, ; Verweij et al, ) regardless of its nature (Kramer & Davenport, ), thereby enhancing the light‐responses of Mbs (Figure ). It is important to point out, that in the absence of a specific and selective blocker of the HC‐mediated inhibition in the outer retina, we could not reverse the order of eliminating inner and outer retinal inhibition of Mbs: although applying NBQX first would have eliminated the HC‐mediated outer retinal inhibition, it could also reduce GABA A/C ‐mediated reciprocal feedback to Mb terminals (Vigh & von Gersdorff, ) by blocking Mb‐to‐AC communication as it has been shown recently in paired recordings (Kim & von Gersdorff, ).…”