Synaptic Remodeling in the Cone Pathway After Early Postnatal Horizontal Cell Ablation

Area of Science:

• Neuroscience
• Retinal Biology
• Synaptic Plasticity

Background:

• The visual pathway's initial synapse involves photoreceptors, horizontal cells, and bipolar cells.
• Horizontal cells are crucial for forming invaginating synapses in rod photoreceptors.
• The impact of horizontal cell ablation on cone photoreceptor synapses is not well understood.

Purpose of the Study:

• To investigate the effects of horizontal cell ablation on cone photoreceptor synaptic connections during mouse retinal development.
• To understand how cones adapt and form new synaptic connections in the absence of horizontal cells.

Main Methods:

• Selective ablation of horizontal cells in developing mouse retinas around postnatal day 4/5.
• Analysis of cone photoreceptor morphology and synaptic connections using light and electron microscopy.
• Assessment of synaptic remodeling and expression of synaptic proteins in adult retinas.

Main Results:

• Cone photoreceptors initially formed normal flat contacts with OFF bipolar cells but reduced invaginating contacts with ON bipolar cells after horizontal cell ablation.
• Significant synaptic remodeling occurred, including cone terminal clustering and mislocalization of cone somata.
• Adult cones developed highly branched axons with numerous terminals, and OFF bipolar cells formed new putative synapses with cones, expressing glutamate receptors.

Conclusions:

• Early horizontal cell ablation leads to differential remodeling of cone bipolar cell synapses: loss of ON bipolar cell connections and formation of new OFF bipolar cell synapses.
• Cone photoreceptors can form new synaptic connections with OFF bipolar cells, suggesting plasticity in the visual pathway.
• Synapse formation and maintenance are differentially regulated for flat versus invaginating contacts at cone terminals, highlighting the critical role of horizontal cells.