Nonlinear dendritic integration of electrical and chemical synaptic inputs drives fine-scale correlations

Trenholm, Stuart; McLaughlin, Amanda J.; Schwab, David J.; Turner, Maxwell H.; Smith, Robert G.; Rieke, Fred; Awatramani, Gautam B.

doi:10.1038/nn.3851

Cited by 76 publications

(66 citation statements)

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“…By influencing neurotransmitter release from bipolar cell axons, lateral spread of signals among neighboring bipolar cells can selectively enhance bipolar synaptic output in response to low contrast stimuli that occur closely in space and time. Recent work demonstrates an important role for electrical coupling in postsynaptic integration of combined electrical and chemical synaptic inputs (Trenholm et al, 2013b; Trenholm et al, 2014; Vervaeke et al, 2012), and in controlling steady-state release properties of chemical synapses (Grimes et al, 2014); our results complement these findings to highlight how electrical and chemical synapses can work in concert to dictate circuit function.…”

Section: Discussionsupporting

confidence: 73%

Nonlinear Spatiotemporal Integration by Electrical and Chemical Synapses in the Retina

Kuo

Schwartz

Rieke

2016

Neuron

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100

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Summary Electrical and chemical synapses coexist in circuits throughout the CNS. Yet, it is not well understood how electrical and chemical synaptic transmission interact to determine the functional output of networks endowed with both types of synapse. We found that release of glutamate from bipolar cells onto retinal ganglion cells (RGCs) was strongly shaped by gap junction-mediated electrical coupling within the bipolar cell network of the mouse retina. Specifically, electrical synapses spread signals laterally between bipolar cells, and this lateral spread contributed to a nonlinear enhancement of bipolar cell output to visual stimuli presented closely in space and time. Our findings thus (1) highlight how electrical and chemical transmission can work in concert to influence network output, and (2) reveal a previously unappreciated circuit mechanism that increases RGC sensitivity to spatiotemporally correlated input, such as that produced by motion.

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Section: Discussionsupporting

confidence: 73%

Nonlinear Spatiotemporal Integration by Electrical and Chemical Synapses in the Retina

Kuo

Schwartz

Rieke

2016

Neuron

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100

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“…Importantly, probing the DSGC's receptive field with small spots activates local regions of the DSGC's receptive field, distinct from large low‐contrast spot stimuli (Trenholm et al . ).…”

Section: Discussionmentioning

confidence: 97%

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

Sethuramanujam

Awatramani

Slaughter

2018

The Journal of Physiology

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Starburst amacrine cells release GABA and ACh. This study explores the coordinated function of starburst-mediated cholinergic excitation and GABAergic inhibition to bistratified retinal ganglion cells, predominantly direction-selective ganglion cells (DSGCs). In rat retina, under our recording conditions, starbursts were found to provide the major excitatory drive to a sub-population of ganglion cells whose dendrites co-stratify with starburst dendrites (putative DSGCs). In mouse retina, recordings from genetically identified DSGCs at physiological temperatures reveal that ACh inputs dominate the response to small spot-high contrast light stimuli, with preferential addition of bipolar cell input shifting the balance towards glutamate for larger spot stimuli In addition, starbursts also appear to gate glutamatergic excitation to DSGCs by postsynaptic and possibly presynaptic inhibitory processes ABSTRACT: Starburst amacrine cells release both GABA and ACh, allowing them to simultaneously mediate inhibition and excitation. However, the precise pre- and postsynaptic targets for ACh and GABA remain under intense investigation. Most previous studies have focused on starburst-mediated postsynaptic GABAergic inhibition and its role in the formation of directional selectivity in ganglion cells. However, the significance of postsynaptic cholinergic excitation is only beginning to be appreciated. Here, we found that light-evoked responses measured in bi-stratified rat ganglion cells with dendrites that co-fasciculate with ON and OFF starburst dendrites (putative direction-selective ganglion cells, DSGCs) were abolished by the application of nicotinic receptor antagonists, suggesting ACh could act as the primary source of excitation. Recording from genetically labelled DSGCs in mouse retina at physiological temperatures revealed that cholinergic synaptic inputs dominated the excitation for high contrast stimuli only when the size of the stimulus was small. Canonical glutamatergic inputs mediated by bipolar cells were prominent when GABA/glycine receptors were blocked or when larger spot stimuli were utilized. In mouse DSGCs, bipolar cell excitation could also be unmasked through the activation of mGluR2,3 receptors, which we show suppresses starburst output, suggesting that GABA from starbursts serves to inhibit bipolar cell signals in DSGCs. Taken together, these results suggest that starbursts amplify excitatory signals traversing the retina, endowing DSGCs with the ability to encode fine spatial information without compromising their ability to encode direction.

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“…DSGCs in rabbit retina generate dendritic sodium spikes that significantly sharpen DS tuning (Oesch et al, 2005; Sivyer and Williams, 2013), and a different DSGC subtype in mouse employs both dendritic spikes and gap junction-mediated interconnectivity to synchronize and temporally advance the timing of DS signaling (Trenholm et al, 2014; Trenholm et al, 2013). We did not detect dendritic spikes in DRD4 DSGCs (data not shown), and our computer simulations did not require regenerative dendritic events to replicate experimentally recorded PSP and (somatic) AP responses and DSI values, suggesting that passive PSP propagation to the soma is sufficient to generate reliable DS detection in these DSGCs.…”

Section: Discussionmentioning

confidence: 99%

NMDA Receptors Multiplicatively Scale Visual Signals and Enhance Directional Motion Discrimination in Retinal Ganglion Cells

Poleg-Polsky

Diamond

2016

Neuron

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SUMMARY Postsynaptic responses in many CNS neurons are typically small and variable, often making it difficult to distinguish physiologically relevant signals from background noise. To extract salient information, neurons are thought to integrate multiple synaptic inputs and/or selectively amplify specific synaptic activation patterns. Here, we present evidence for a third strategy: directionally selective ganglion cells (DSGCs) in the mouse retina multiplicatively scale visual signals via a mechanism that requires both nonlinear NMDA receptor (NMDAR) conductances in DSGC dendrites and directionally tuned inhibition provided by the upstream retinal circuitry. Postsynaptic multiplication enables DSGCs to discriminate visual motion more accurately in noisy visual conditions without compromising directional tuning. These findings demonstrate a novel role for NMDARs in synaptic processing and provide new insights into how synaptic and network features interact to accomplish physiologically relevant neural computations.

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Nonlinear dendritic integration of electrical and chemical synaptic inputs drives fine-scale correlations

Cited by 76 publications

References 50 publications

Nonlinear Spatiotemporal Integration by Electrical and Chemical Synapses in the Retina

Nonlinear Spatiotemporal Integration by Electrical and Chemical Synapses in the Retina

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

NMDA Receptors Multiplicatively Scale Visual Signals and Enhance Directional Motion Discrimination in Retinal Ganglion Cells

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