Development of spontaneous and glutamate-evoked activity is altered by chronic ethanol in cultured cerebellar Purkinje neurons.
The effects of continuous exposure to ethanol on the cytological and physiological development of a central nervous system (CNS) neuron were studied using the cultured Purkinje neuron of the rat cerebellar cortex. Purkinje neurons in fetal rat brain cultures which are established at one day before birth show development comparable to that described in vivo in other studies. In culture, Purkinje neurons progress from immature rounded cells with fine neurites to mature neurons with a branched dendritic structure. These structural changes are accompanied by an increase in the duration and complexity of the excitatory response to glutamate, by transitions in the patterns of spontaneous activity, and by an increase in mean firing rate. Our results demonstrate that chronic exposure to a low concentration of ethanol (90 mg%; 19.5 mM) during development selectively alters the electrophysiological but not the morphological properties of Purkinje neurons. Specifically, ethanol treatment reduces the responsiveness of these neurons to glutamate, delays the expected developmental transitions in patterns of spontaneous activity, and induces increased spontaneous bursting activity, particularly at the stage of dendritic formation. Impairment of responsiveness to glutamate is significant in that it may reflect the compromise by ethanol of a major excitatory pathway in the cerebellar cortex, resulting from the decreased efficacy of glutamatergic input from parallel fibers. In contrast to the results of other studies using adult neurons as a model for the effects of ethanol, our work suggests that the developing CNS neuron does not become tolerant; that is, in the continuing presence of ethanol, it does not express physiological function equivalent to that of the control.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D009419:Nerve Tissue Proteins / Q000032:analysis; D011689:Purkinje Cells / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D016704:Synapsins
D005971:Glutamates; D009419:Nerve Tissue Proteins; D016704:Synapsins; D000431:Ethanol; D018698:Glutamic Acid