L-type calcium channel agonist induces correlated depolarizations in mice lacking the beta2 subunit nAChRs.
Retinal waves are mediated in part by activation of nicotinic receptors containing the beta2 subunit. Mice deficient in beta2 containing nAChRs have maintained firing of action potentials but do not support correlated waves. As a result, beta2-/- 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 beta2-/- retina by pharmacological application of the L-type calcium channel agonist, FPL-64176. Here, we characterize FPL-induced activity patterns in beta2-/- retina using both whole cell and multielectrode array recordings. FPL-induced strong depolarizations in previously non-spiking beta2-/- 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 beta2-/- 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 beta2-/- mice.
Torborg
Christine
C
Neurobiology Section 0357, Division of Biological Sciences, UCSD, 9500 Gilman Drive, La Jolla, CA 92093-0357, USA.
Wang
Chih-Tien
CT
Muir-Robinson
Gianna
G
Feller
Marla B
MB
D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004594:Electrophysiology; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D011758:Pyrroles / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D011758:Pyrroles; D011978:Receptors, Nicotinic; C071658:FPL 64176