alpha_2-ADRENOCEPTOR REGULATES THE SPONTANEOUS AND THE GABA/GLUTAMATE MODULATED FIRING ACTIVITY OF THE RAT MEDIAL PREFRONTAL CORTEX PYRAMIDAL NEURONS

摘要

The spontaneous and event-related firing activity of the medial prefrontal cortex (mPFC) pyramidal neurons are modulated mainly by glutamatergic inputs and GABAergic afferents. Substantial data demonstrate that alpha_2-adrenocep-tors also play specific roles in the regulation of the firing of these pyramidal neurons. In the present study, the effects of alpha_2-adrenoceptor agents on spontaneous, GABA- and gluta-mate-mediated firing of mPFC pyramidal neurons were examined in anaesthetized rats. Microiontophoresis of norepi-nephrine (NE, 30 nA) decreased the spontaneous firing rate in the majority of the pyramidal neurons (25/36) and induced unchanged (six out of 36) or excitatory (five out of 36) effects in a minority of the pyramidal neurons. The inhibitory effect of NE was reproduced by alpha_2-adrenoceptor agonist clonidine (40 nA) and blocked by alpha_2-adrenoceptor antagonist idazoxan (15 nA). Clonidine application (2-5 nA) enhanced the inhibitory responses to GABA administration in the most of the pyramidal neurons examined (seven out of 12). Clonidine with low current intensity (2-5 nA) did not significantly modulate the excitatory effect of glutamate ejection on firing rate of the pyramidal neurons for both the absolute effect and the percentage of excitation. In contrast, the absolute excitatory effect of glutamate was not significantly strengthened in the presence of clonidine with high current intensity (20-40 nA) but the percentage of excitation by glutamate was increased. These results indicate that the inhibitory effects of NE on spontaneous firing of the mPFC pyramidal neurons are mediated by alpha_2-adrenoceptors, whereas alpha_2-adrenoceptors stimulation enhanced GABA-mediated inhibition and play a specific part in modulation of glutamate-mediated excitation on the neurons.