Differential Expression Analysis Identifies Candidate Synaptogenic Molecules for Wiring Direction-Selective Circuits...

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Neural circuits exhibit specific synaptic connections, exemplified by retinal direction-selective (DS) circuits.
• Starburst amacrine cells (SACs) form selective connections with DS retinal ganglion cell (DSGC) subtypes, crucial for motion detection.

Purpose of the Study:

• To investigate the molecular basis of specific synaptic wiring in DS retinal circuits.
• To identify unique gene expression profiles in DSGC subtypes that may guide SAC connectivity.
• To test the role of candidate molecules, such as cerebellin-4 (Cbln4), in the development of DS tuning.

Main Methods:

• Paired recordings in isolated mouse retinas to determine synapse formation timing (postnatal day 10).
• RNA sequencing and differential expression analysis of isolated ON-OFF DSGCs.
• Conditional knockout of Cbln4 and subsequent two-photon calcium imaging and whole-cell voltage-clamp recordings.

Main Results:

• Postnatal day 10 is identified as a critical period for asymmetric synapse formation in DS circuits.
• Transcriptomic analysis revealed candidate molecules potentially involved in direction-specific wiring.
• Mice lacking Cbln4 showed a slight deficit in directional tuning in ventral-preferring DSGCs, but no significant change in inhibitory inputs was detected.

Conclusions:

• Cbln4 does not appear to primarily act through a cell-autonomous mechanism to instruct DS circuit wiring.
• The study identified novel candidate factors that warrant further investigation into the molecular mechanisms of synaptic specificity in the DS circuit.