Extrasynaptic glutamate and inhibitory neurotransmission modulate ganglion cell participation during glutamatergic retinal waves

Abstract

Firl A, Sack GS, Newman ZL, Tani H, Feller MB. Extrasynaptic glutamate and inhibitory neurotransmission modulate ganglion cell participation during glutamatergic retinal waves. J Neurophysiol 109: 1969 -1978, 2013. First published January 23, 2013 doi:10.1152/jn.00039.2013.-During the first 2 wk of mouse postnatal development, transient retinal circuits give rise to the spontaneous initiation and lateral propagation of depolarizations across the ganglion cell layer (GCL). Glutamatergic retinal waves occur during the second postnatal week, when GCL depolarizations are mediated by ionotropic glutamate receptors. Bipolar cells are the primary source of glutamate in the inner retina, indicating that the propagation of waves depends on their activation. Using the fluorescence resonance energy transfer-based optical sensor of glutamate FLII81E-1, we found that retinal waves are accompanied by a large transient increase in extrasynaptic glutamate throughout the inner plexiform layer. Using two-photon Ca 2ϩ imaging to record spontaneous Ca 2ϩ transients in large populations of cells, we found that despite this spatially diffuse source of depolarization, only a subset of neurons in the GCL and inner nuclear layer (INL) are robustly depolarized during retinal waves. Application of the glutamate transporter blocker dl-threo-␤-benzyloxyaspartate (25 M) led to a significant increase in cell participation in both layers, indicating that the concentration of extrasynaptic glutamate affects cell participation in both the INL and GCL. In contrast, blocking inhibitory transmission with the GABA A receptor antagonist gabazine and the glycine receptor antagonist strychnine increased cell participation in the GCL without significantly affecting the INL. These data indicate that during development, glutamate spillover provides a spatially diffuse source of depolarization, but that inhibitory circuits dictate which neurons within the GCL participate in retinal waves. retina; development; retinal waves; glutamate spillover; crossover inhibition

CaV3.2 KO mice have altered retinal waves but normal direction selectivity

“…First, several cell types in the circuit that mediate retinal waves – including bipolar cells, starburst amacrine cells and DSGCs – are depolarized during these waves (Zhou, 1998; Elstrott & Feller, 2010; Ford et al , 2012; Firl et al , 2013; Akrouh & Kerschensteiner, 2013). Thus they are robustly activated by spontaneous activity.…”

“…Glutamatergic waves are mediated by glutamate release from bipolar cells (Firl et al , 2013; Akrouh & Kerschensteiner, 2013), however which aspects of the circuit control burst properties and the frequency of waves are not yet identified. In the retina, T-type channels have been described in bipolar cell terminals and retinal ganglion cells (Ma & Pan, 2003; Pan et al , 2001; Lee et al , 2003; Hu et al , 2009; Cui et al , 2012; Sargoy et al , 2014).…”

“…A critical component of the network mediating waves and a primary source of depolarizing input to RGCs is glutamate release from bipolar cells (Firl et al , 2013; Akrouh & Kerschensteiner, 2013). In the adult retina, bipolar cells exhibit unstable membrane potentials and their spontaneous depolarizations are mediated by low-voltage activated T-type calcium channels (Ma & Pan, 2003; Cueni et al , 2009; Sargoy et al , 2014; Puthussery et al , 2014) that are expressed in subsets of bipolar cells (Pan et al , 2001; Singer & Diamond, 2003) and of ganglion cells (Sargoy et al , 2014).…”

Copper is an endogenous modulator of neural circuit spontaneous activity

“…5). Retinas were acutely isolated from P10−P13 mice and bolus loaded with OGB as previously described (52). Spontaneous calcium transients propagated across the GCL with a welldefined periodic frequency (Fig.…”

GABAergic regulation of spontaneous spike patterns in the developing rabbit retina

“…Thus, our study suggests that the emergence of inhibition from amacrine cells plays an important role in shaping and regulating the diverse spike patterns of ganglion cells. On the other hand, because bipolar cells also participate in stage III waves [2,7], an additional possibility of a developmental GABAergic contribution at the outer plexiform layer cannot be excluded.…”