EVIDENCE FOR PRETERMINAL NICOTINIC RECEPTORS ON GABAERGIC AXONS IN THE RAT INTERPEDUNCULAR NUCLEUS

Presynaptic nicotinic ACh receptors (nAChRs) are abundant in the nervo us system, where they are thought to regulate the release of various n eurotransmitters. Whole-cell recordings performed on rat interpeduncul ar nucleus neurons using the thin-slice technique showed that nicotine dramatically increased the frequency of postsynaptic GABAergic curren ts. This effect was observed at low micromolar concentration of agonis t; it was mimicked by cytisine, dimethyl-phenylpiperazinium, and ACh i n the presence of eserine. It was blocked by hexamethonium, dihydro-be ta-erythroidine, and mecamylamine. The presynaptic action was suppress ed in the presence of TTX. A comparable effect of nicotine was found u sing a preparation of acutely isolated neurons that had retained synap tic terminals attached to their cell body as evidenced by immunoreacti vity to synaptophysin and presence of spontaneous GABAergic and glutam atergic synaptic activity. Nicotinic agonists increased the frequency of GABAergic postsynaptic currents, an effect blocked by curare and me camylamine. This action was also suppressed in the presence of TTX. Th ese data suggest the presence of nAChRs at a preterminal level on axon s of intrinsic GABAergic neurons. We propose that, in contrast to pres ynaptic nAChRs, activation of these ''preterminal'' nAChRs can trigger a spike discharge and thus have a generalized action on the GABAergic afferent.