ORGANOTYPIC BRAIN SLICE CULTURES FOR FUNCTIONAL-ANALYSIS OF ALCOHOL-RELATED DISORDERS - NOVEL VERSUS CONVENTIONAL PREPARATIONS

Assessment of long-term alterations in neural function and phenotype h as usually involved culture techniques that utilize dissociated prepar ations. Recently, we have approached such topics in alcohol research b y using brain slice cultures, also known as explant or organotypic pre parations. In this symposium presentation, two preparations will be di scussed, and examples of the particular advantages of these preparatio ns will be presented in relation to alcohol research. First, we use th e hippocampal exp;ant preparation for assessment of long-term alterati ons in N-methyl-D-aspartate receptor (NMDAR) function due to chronic e thanol exposure and subsequent withdrawal. This preparation displays m any synaptic, structural, and enzymatic phenotypes indicative of norma l neural preparations. Patch clamp recordings reveal NMDAR-mediated ex citatory postsynaptic current (EPSC) elicited upon stimulation of Scha ffer collateral fibers and recorded from CA1 pyramidal cells. Long-ter m ethanol exposure followed by subsequent withdrawal resulted in a spe cific enhancement of NMDAR-mediated synaptic responses which preceded the expression of epileptiform events that occurred after prolonged wi thdrawal periods. Second, we describe a navel explant preparation, der ived from horizontal slices of the entire forebrain and midbrain of th e rat. These long-term explants displayed multiple normal phenotypes i ncluding Nissl, AChE, TH, and GFAP staining. Electrophysiologically, t hese explants displayed a functional corticostriatal pathway recorded with field and patch clamp techniques and elicited by synaptic stimula tion. Taken together, these explant preparations display utility for l ong-term study of ethanol effects on neural systems, especially relati ng to withdrawal hyperexcitability as well as systems involved in drug -seeking behavior.