Abstract
The mechanism underlying a presynaptic GABAB receptor-mediated inhibition of transmitter release has been characterized for a variety of synapses in the central nervous system. These studies have suggested a range of transduction mechanisms, including the activation of adenylate cyclase and the closure of K+ and Ca2+ channels via G-coupled proteins. We have examined the intracellular signaling pathways underlying baclofen-induced inhibition of transmitter release in autaptic synapses of isolated mouse hippocampal neurons by using patch-clamp recording methods. Baclofen, a selective GABAB receptor agonist, reversibly decreased both the amplitude of evoked postsynaptic currents (ePSCs) and the frequency of spontaneously occurring miniature postsynaptic currents (mPSCs). During the inhibition of mPSCs frequency, the mean amplitude of mPSCs did not show any significant alternations. These observations suggest that baclofen inhibits synaptic transmission by presynaptic mechanism. To clarify the intracellular mechanisms of the observed presynaptic inhibition by baclofen, the effects of Ca2+-free extracellular solution were studied. In the absence of extracellular Ca2+, baclofen blocked ePSC and reduced the frequency of mPSCs. The results might suggest that baclofen inhibits neurotransmitter release downstream of Ca2+ entry and may directly affect the exocytotic machinery at the presynaptic terminal. [Jpn J Physiol 55 Suppl:S151 (2005)]
