Title

Disruption and recovery of patterned retinal activity in the absence of acetylcholine.

Document Type

Article

Publication Date

2005

Keywords

Animals-Newborn, Body-Patterning, Calcium-Signaling, Choline-O-Acetyltransferase, Comparative-Study, In-Vitro, Mice, Mice-Inbred-C57BL, Mice-Knockout, Research-Support-N, I, H, -Extramural, Research-Support-U, S, -Gov't-Non-P, H, S, Research-Support-U, S, -Gov't-P, H, S, Retina, Synaptic-Transmission

JAX Source

J Neurosci 2005 Oct; 25(41):9347-57.

Abstract

Many developing neural circuits generate synchronized bursting activity among neighboring neurons, a pattern thought to be important for sculpting precise neural connectivity. Network output remains relatively constant as the cellular and synaptic components of these immature circuits change during development, suggesting the presence of homeostatic mechanisms. In the retina, spontaneous waves of activity are present even before chemical synapse formation, needing gap junctions to propagate. However, as synaptogenesis proceeds, retinal waves become dependent on cholinergic neurotransmission, no longer requiring gap junctions. Later still in development, waves are driven by glutamatergic rather than cholinergic synapses. Here, we asked how retinal activity evolves in the absence of cholinergic transmission by using a conditional mutant in which the gene encoding choline acetyltransferase (ChAT), the sole synthetic enzyme for acetylcholine (ACh), was deleted from large retinal regions. ChAT-negative regions lacked retinal waves for the first few days after birth, but by postnatal day 5 (P5), ACh-independent waves propagated across these regions. Pharmacological analysis of the waves in ChAT knock-out regions revealed a requirement for gap junctions but not glutamate, suggesting that patterned activity may have emerged via restoration of previous gap-junctional networks. Similarly, in P5 wild-type retinas, spontaneous activity recovered after a few hours in nicotinic receptor antagonists, often as local patches of coactive cells but not waves. The rapid recovery of rhythmic spontaneous activity in the presence of cholinergic antagonists and the eventual emergence of waves in ChAT knock-out regions suggest that homeostatic mechanisms regulate retinal output during development.