Cross-compartmental Modulation of Dendritic Signals for Retinal Direction Selectivity

Abstract

Summary Compartmentalized signaling in dendritic subdomains is critical for the function of many central neurons. In the retina, individual dendritic sectors of a starburst amacrine cell (SAC) are preferentially activated by different directions of linear motion, indicating limited signal propagation between the sectors. However, the mechanism that regulates this propagation is poorly understood. Here, we find that metabotropic glutamate receptor 2 (mGluR2) signaling, which acts on voltage-gated calcium channels in SACs, selectively restricts cross-sector signal propagation in SACs, but does not affect local dendritic computation within individual sectors. mGluR2 signaling ensures sufficient electrotonic isolation of dendritic sectors to prevent their depolarization during non-preferred motion, yet enables controlled multicompartmental signal integration that enhances responses to preferred motion. Furthermore, mGluR2-mediated dendritic compartmentalization in SACs is important for the functional output of direction-selective ganglion cells (DSGCs). Therefore, our results directly link modulation of dendritic compartmentalization to circuit-level encoding of motion direction in the retina.

Antagonistic center-surround mechanisms for direction selectivity in the retina

“…We presented On-SAC with expanding (CF motion) and collapsing (CP motion) drifting rings centered on the cell's soma while recording SAC somatic voltage in current-clamp mode ( Figure 2A). In accordance with previous reports, dark adapted (DA) On-SAC displayed stronger depolarization in response to CF than to CP motion (Figure 2A, B, top) (Ding et al, 2016;Euler et al, 2002;Fransen and Borghuis, 2017;Koren et al, 2017). The CF preference was reflected by a positive annular direction selective index (A-DSI; see Methods; A-DSIDA = 0.19 ± 0.2; Figure 2C).…”

“…Starburst amacrine cells (SAC) mediate the directional response via asymmetric wiring, as only processes oriented in the DSGC's null direction tend to form inhibitory synapses on its dendrites ( Figure 1A) (Briggman et al, 2011). Although SAC somatic voltage shows no directional preference to linear motion, its processes act as autonomous units with directional preference, responding with greater depolarization to motion away from the cell soma (centrifugal; CF) than to motion towards cell soma (centripetal; CP) (Ding et al, 2016;Euler et al, 2002;Fransen and Borghuis, 2017;Koren et al, 2017). Due to their wiring specificity, SAC processes that innervate a given DSGC display directional preference to its null direction, which is expected to result in stronger GABA release during null motion than during preferred motion.…”

Cholinergic excitation complements glutamate in coding visual information in retinal ganglion cells

“…Recent physiological studies show that mGluR2 signalling is specific to starbursts in the retina, and reduces the activity of N/P/Q type voltage‐gated calcium channels (Koren et al . ), known to be critical for starburst neurotransmitter release (Lee et al . ).…”

“…Recent physiological studies show that mGluR2 signalling is specific to starbursts in the retina, and reduces the activity of N/P/Q type voltage-gated calcium channels (Koren et al 2017), known to be critical for starburst neurotransmitter release (Lee et al 2010). Immunohistochemistry indicates that the mGluR2 receptor is found exclusively on cholinergic amacrine cells in the inner retina (Koulen et al 1996;Yoshida et al 2001), and indeed the activation of mGluR2 reduces directional selectivity of ganglion cells by enhancing their null spiking response (Jensen, 2006).…”

Regional differences in Purkinje cell morphology in the cerebellar vermis of male mice

“…Dendritic branch points can have important consequences for the propagation of signals within a neuron; differences in dendritic arbor morphology could therefore influence how PCs integrate synaptic input (Branco & Hausser, ; Larkum & Nevian, ). In particular, dendritic branches act to compartmentalize the cell by limiting signal propagation between dendritic sectors (Branco & Hausser, ; Koren, Grove, & Wei, ); the presence of two primary dendrites could therefore influence the integration of parallel fiber input within PCs. Given that 67% of lobule IX PCs had two primary dendrites in the present study, this could in turn affect the neuronal computations occurring in this region.…”