L-type calcium channel agonist induces correlated depolarizations in mice lacking the β2 subunit nAChRs

Abstract Retinal waves are mediated in part by activation of nicotinic receptors containing the β2 subunit. Mice deficient in β2 containing nAChRs have maintained firing of action potentials but do not support correlated waves. As a result, β2−/− mice have inhibited refinement of circuits within the retina as well as retinal projections to the CNS. Previously, we observed that correlated increases in calcium reminiscent of retinal waves could be induced in β2−/− retina by pharmacological application of the L-type calcium channel agonist, FPL-64176. Here, we characterize FPL-induced activity patterns in β2−/− retina using both whole cell and multielectrode array recordings. FPL-induced strong depolarizations in previously non-spiking β2−/− retinal ganglion cells. Though these strong depolarizations were likely to underlie the FPL-induced calcium transients, they led to highly variable effects on the spiking of individual retinal ganglion cells. In addition, induced spiking activity had significantly weaker nearest-neighbor correlations than WT mice. Initial attempts of intraocular injections of FPL in β2−/− mice did not rescue eye-specific layer formation. These findings indicate that activity induced by FPL is not sufficient for driving eye-specific segregation in β2−/− mice.