CHRONIC EXPOSURE TO ALCOHOL DURING DEVELOPMENT ALTERS THE MEMBRANE-PROPERTIES OF CEREBELLAR PURKINJE NEURONS IN CULTURE

The active and passive membrane properties of developing Purkinje neurons in control cultures and cultures chronically treated with 20 or 40 mM ethanol for 1 or 2 weeks were examined using whole-cell current-clamp techniques. The membrane properties were characterized by the features of the voltage responses evoked by intracellular current injection of a series of depolarizing and hyperpolarizing current pulses. Analysis of these responses and background spontaneous activity showed several differences between the control and ethanol-treated Purkinje neurons: (1) membrane input resistance was significantly larger in the ethanol-treated neurons; (2) the percentage of neurons exhibiting immature firing patterns was significantly higher in the ethanol-treated neurons; (3) the afterhyperpolarization following a current-evoked train of action potentials was significantly larger in the ethanol-treated neurons; (4) spontaneous activity (synaptic potentials and synaptically evoked spike events) was significantly reduced in neurons treated with 40 mM ethanol for 1 week; spontaneous activity in neurons treated with 20 mM ethanol for 1 or 2 weeks was similar to that observed in the control group. These differences indicate that ethanol exposure during development directly alters the physiological properties of this CNS neuronal type. These neuronal actions of ethanol may contribute to the behavioral deficits observed in animal models of fetal alcohol syndrome. Similar target sites of ethanol action are likely to be present in the human CNS neurons and may be involved in human fetal alcohol syndrome.