Differences in the expression of GABA_A receptors between functionally innervated and non-innervated granule neurons in neonatal rat cerebellar cultures

We had earlier found that granule neurons in cultures of small explants of neonatal rat cerebellar cortex could be placed in two groups: cells in one group showed spontaneous synaptic activity and also had a large response to applications of 1 μM γ-aminobutyric acid (GABA) while cells in the other lacked spontaneous activity and also showed much lower sensitivity to GABA [25]. For convenience, the more responsive cells will be termed A-type neurons, while the less responsive cells will be termed B-type. We have undertaken a comparison of the responses mediated by activation of GABA_A receptors for the two types of neurons. A-type neurons have a larger maximal response to GABA (about 10 times that for B-type neurons), suggesting that they express more functional GABA_A receptors. The concentration of GABA producing half-maximal activation of A-type neurons is somewhat less (12 μM) than that for B-type neurons (41 μM), while the Hill coefficients are similar. Responses of both types of cell desensitize to prolonged applications 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 lesser extent by either chlordiazepoxide or alphaxalone than are the responses of B-type neurons, indicating that the pharmacological properties of the receptors differ. These data indicate that A-type and B-type granule neurons in our cultures express GABA_A receptors which differ in number, physiological properties and pharmacological responsiveness. We have also confirmed the observation that almost all A-type neurons also show spontaneous synaptic currents, while almost no B-type neurons do.