Requirements for synaptically evoked plateau potentials in relay cells of the dorsal lateral geniculate nucleus of the mouse.

Abstract

In developing cells of the mouse dorsal lateral geniculate nucleus (dLGN), synaptic responses evoked by optic tract (OT) stimulation give rise to long-lasting, high-amplitude depolarizations known as plateau potentials. These events are mediated by L-type Ca2+ channels and occur during early postnatal life, a time when retinogeniculate connections are remodelling. To better understand the relationship between L-type activity and dLGN development we used an in vitro thalamic slice preparation which preserves the retinal connections and intrinsic circuitry in dLGN and examined how synaptic responses evoked by OT stimulation lead to the activation of plateau potentials. By varying the strength and temporal frequency of OT stimulation we identified at least three factors that contribute to the developmental regulation of plateau activity: the degree of retinal convergence, the temporal pattern of retinal stimulation and the emergence of feed-forward inhibition. Before natural eye opening (postnatal day 14), the excitatory synaptic responses of relay cells receiving multiple retinal inputs summated in both the spatial and temporal domains to produce depolarizations sufficient to activate L-type activity. After eye opening, when inhibitory responses are fully developed, plateau activity was rarely evoked even with high temporal rates of OT stimulation. When the bulk of this inhibition was blocked by bath application of bicuculline, the incidence of plateau activity increased significantly. We also made use of a transgenic mouse that lacks the β3 subunit of the L-type Ca2+ channel. These mutants have far fewer membrane-bound Ca2+ channels and attenuated L-type activity. In β3 nulls, L-type plateau activity was rarely observed even at young ages when plateau activity prevails. Thus, in addition to the changing patterns of synaptic connectivity and retinal activity, the expression of L-type Ca2+ channels is a requisite component in the manifestation of plateau activity.