Activity-dependent development of synaptic circuits mediates direction selectivity in an axis-specific manner
Karina Bistrong1, Rachana Deven Somaiya1, Eugene Y Liang2
1Department of Neuroscience & Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell Reports
|June 25, 2025
Summary
Spontaneous activity shapes vision development. In mice lacking cholinergic retinal waves, the loss of horizontal direction selectivity impairs the optokinetic reflex (OKR), highlighting the role of early neural activity in forming motion detection circuits.
Area of Science:
- Neuroscience
- Developmental Biology
- Visual System Research
Background:
- The optokinetic reflex (OKR) stabilizes retinal images during navigation, originating from direction-selective ganglion cells (DSGCs).
- Cholinergic retinal waves are crucial for developing visual processing, including direction selectivity.
- The β2-nAChR-KO mouse model lacks these waves, exhibiting deficits in horizontal direction selectivity but retaining vertical direction selectivity.
Purpose of the Study:
- To investigate the impact of absent cholinergic retinal waves on horizontal and vertical OKR in β2-nAChR-KO mice.
- To examine asymmetric inhibition in DSGCs in the absence of cholinergic retinal waves.
- To elucidate the role of spontaneous neural activity in the formation of motion detection circuits.
Main Methods:
- Utilizing the β2-nAChR-KO mouse model lacking cholinergic retinal waves.
- Assessing the optokinetic reflex (OKR) along horizontal and vertical axes.
- Performing dual whole-cell voltage-clamp recordings to analyze synaptic conductances.
- Investigating asymmetric inhibition onto horizontal- and vertical-preferring DSGCs.
Main Results:
- β2-nAChR-KO mice showed a loss of horizontal OKR, correlating with diminished asymmetric inhibition onto horizontal-preferring DSGCs.
- Vertical OKR and asymmetric inhibition onto vertical-preferring DSGCs were preserved.
- Reduced GABAergic conductance between horizontal-preferring DSGCs and their presynaptic partners underlies the observed decrease in asymmetric inhibition.
Conclusions:
- Absence of horizontal direction selectivity in β2-nAChR-KO mice leads to impaired horizontal OKR.
- Spontaneous activity, specifically cholinergic retinal waves, is essential for the precise wiring required for horizontal motion detection.
- These findings underscore the critical role of early, spontaneous neural activity in shaping visual circuit development before vision onset.
