DIFFERENCES IN THE EXPRESSION OF GABA(A) RECEPTORS BETWEEN FUNCTIONALLY INNERVATED AND NONINNERVATED GRANULE NEURONS IN NEONATAL RAT CEREBELLAR CULTURES

We had earlier found that granule neurons in cultures of small explant s of neonatal rat cerebellar cortex could be placed in two groups: cel ls in one group showed spontaneous synaptic activity and also had a la rge response to applications of 1 mu M gamma-aminobutyric acid (GABA) while cells in the other lacked spontaneous activity and also showed m uch lower sensitivity to GABA [25]. For convenience, the more responsi ve cells will be termed A-type neurons, while the less responsive cell s will be termed B-type. We have undertaken a comparison of the respon ses mediated by activation of GABA(A) receptors for the two types of n eurons. A-type neurons have a larger maximal response to GABA (about 1 0 times that for B-type neurons), suggesting that they express more fu nctional GABA(A) receptors. The concentration of GABA producing half-m aximal activation of A-type neurons is somewhat less (12 mu M) than th at for B-type neurons (41 mu M), while the Hill coefficients are simil ar. Responses of both types of cell desensitize to prolonged applicati ons of GABA. At a given concentration of GABA the responses of A-type neurons desensitize more rapidly than the responses of B-type neurons, indicating that the physiological properties of the receptors differ. Responses of A-type neurons are also potentiated to a significantly l esser extent by either chlordiazepoxide or alphaxalone than are the re sponses of B-type neurons, indicating that the pharmacological propert ies of the receptors differ. These data indicate that A-type and B-typ e granule neurons in our cultures express GABA(A) receptors which diff er in number, physiological properties and pharmacological responsiven ess. We have also confirmed the observation that almost all A-type neu rons also show spontaneous synaptic currents, while almost no B-type n eurons do.