Ethanol Disrupts Immature Network Neuronal Activity Driven by Exci- Tatory Actions of Gaba

ETHANOL DISRUPTS IMMATURE NETWORK NEURONAL ACTIVITY DRIVEN BY EXCITATORY ACTIONS OF GABA. C. F. Valenzuela; R. Galindo. Dept. of Neurosciences, U of New Mexico HSC, Albuquerque, NM 87131, USA. The hippocampus is a brain region that is important for learning and memory processes and studies have demonstrated that it is particularly sensitive to the neuroteratogenic effects of ethanol. In this brain region, there is a developmentally-regulated pattern of network-driven electrical activity known as the giant depolarizing potentials (GDPs). In immature neurons, GABAA receptors are excitatory due to a shift in Clequilibrium potential towards more depolarized potentials. The excitatory actions of GABA generate these GDPs, which are associated with large oscillations in intracellular calcium. These oscillations contribute to activity-dependent modulation of neuronal growth and synaptogenesis by, for example, increasing DNA synthesis and inducing neurotrophic factor expression. Therefore, alterations in this pattern of synaptic activity could have profound effects on the normal maturation of hippocampal circuits. Using acute hippocampal slices from neonatal rats and patch-clamp electrophysiological techniques, it was discovered that ethanol dramatically disrupts GDPs in the CA3 region. Short-term (8 min) application of ethanol (50 mM) increased GDP frequency by 100% 30 (n 12) The increment in GDP activity is likely mediated by an increase in action potential-dependent GABA and glutamate release given that we found that ethanol (50mM) significantly increased the frequency of GABAA receptor-mediated spontaneous postsynaptic currents in pyramidal cells (33% 6; n 12) and interneurons (45% 10; n 11), and of glutamate receptor-mediated spontaneous postsynaptic currents in interneurons (35% 14; n 7). Ethanol did not affect the intrinsic excitability of either interneurons or pyramidal neurons. We are currently investigating if the effect of ethanol involves changes in the probability of GABA or glutamate release. These novel actions of ethanol on immature neuronal circuits are likely to contribute to the pathophysiology of alcohol-related neurodevelopmental disorders and fetal alcohol syndrome. Supported by NIH grant AA12684.