Nearly 50 different mouse retinal ganglion cell (RGC) types sample the visual scene for distinct features. RGC feature selectivity arises from their synapses with a specific subset of amacrine (AC) and bipolar cell (BC) types, but how RGC dendrites arborize and collect input from these specific subsets remains poorly understood. Here we examine the hypothesis that RGCs employ molecular recognition systems to meet this challenge. By combining calcium imaging and type-specific histological stains we define a family of circuits that express the recognition molecule Sidekick 1 (Sdk1) which include a novel RGC type (S1-RGC) that responds to local edges. Genetic and physiological studies revealed that Sdk1 loss selectively disrupts S1-RGC visual responses which result from a loss of excitatory and inhibitory inputs and selective dendritic deficits on this neuron. We conclude that Sdk1 shapes dendrite growth and wiring to help S1-RGCs become feature selective.
Sample registration fields, registration code, and GCaMP6f datasets are available at Dryad (https://doi.org/10.5061/dryad.4xgxd2593).
Data From: The cell adhesion molecule Sdk1 shapes assembly of a retinal circuit that detects localized edgesDryad Digital Repository, doi:10.5061/dryad.4xgxd2593.
Study: Mouse retinal ganglion cell adult atlas and optic nerve crush time seriesBroad Institute Single Cell Portal.
Study: Mouse Retinal Cell Atlas: Molecular Identification of over Sixty Amacrine Cell TypesBroad Institute Single Cell Portal.
Study: Retinal Bipolar Neuron Drop-seqBroad Institute Single Cell Portal.
- Arjun Krishnaswamy
- Arjun Krishnaswamy
- Pierre-Luc Rochon
- Aline Giselle Rangel Olguin
- Aline Giselle Rangel Olguin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Animals were used in accordance with the rules and regulations established by the Canadian Council on Animal Care and protocol (2017-7889) was approved by the Animal Care Committee at McGill University
- Marla B Feller, University of California, Berkeley, United States
© 2021, Rochon et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
The presynaptic protein α-synuclein (αSyn) has been suggested to be involved in the pathogenesis of Parkinson’s disease (PD). In PD, the amygdala is prone to develop insoluble αSyn aggregates, and it has been suggested that circuit dysfunction involving the amygdala contributes to the psychiatric symptoms. Yet, how αSyn aggregates affect amygdala function is unknown. In this study, we examined αSyn in glutamatergic axon terminals and the impact of its aggregation on glutamatergic transmission in the basolateral amygdala (BLA). We found that αSyn is primarily present in the vesicular glutamate transporter 1-expressing (vGluT1+) terminals in mouse BLA, which is consistent with higher levels of αSyn expression in vGluT1+ glutamatergic neurons in the cerebral cortex relative to the vGluT2+ glutamatergic neurons in the thalamus. We found that αSyn aggregation selectively decreased the cortico-BLA, but not the thalamo-BLA, transmission; and that cortico-BLA synapses displayed enhanced short-term depression upon repetitive stimulation. In addition, using confocal microscopy, we found that vGluT1+ axon terminals exhibited decreased levels of soluble αSyn, which suggests that lower levels of soluble αSyn might underlie the enhanced short-term depression of cortico-BLA synapses. In agreement with this idea, we found that cortico-BLA synaptic depression was also enhanced in αSyn knockout mice. In conclusion, both basal and dynamic cortico-BLA transmission were disrupted by abnormal aggregation of αSyn and these changes might be relevant to the perturbed cortical control of the amygdala that has been suggested to play a role in psychiatric symptoms in PD.
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