This proposal is focused on coupling anatomical and electrophysiological techniques to answer questions of location and function of Group II metabotropic glutamate receptors (mGluRs) with the hopes of identifying a novel target for the treatment of absence epilepsy. To do this we will investigate 2 complementary aims.
Aim 1 is the localization of Group II mGluRs within the thalamocortical absence circuitry in an animal model of absence (the ferret) at the light and electron microscopic level. We hypothesize that these receptors are found on presynaptic cortical terminals innervating the TRN, presynaptic TRN terminals innervating the LGN and on TRN dendrites opposing cortical terminals, thus allowing the potential for multiple functions of the Group II mGluRs in the control of cortically-evoked spike-and-wave activity.
Aim 2 is directed at understanding the function of Group II mGluRs in the corticothalamic network. In this aim, we will study the influence of Group II mGluRs on corticothalamic and intra-thalamic synaptic transmission. Furthermore, we will induce absence rhythms in the in vitro slice and investigate whether modulation of Group II mGluRs will reduce these rhythms. We hypothesize that activation of Group II mGluRs will attenuate the cortically driven signal to the thalamus, and this attenuation will reduce the ability of the corticothalamic network to initiate and propagate absence rhythms.
