GABAergic Inhibition: A case for dynamic thinking

Studies of bidirectional synaptic plasticity (long-term potentiation (LTP) and long-term depression (LTD)), a hallmark of learning and memory, have uncovered rapid but long-lasting changes in glutamatergic synaptic function triggered by activity-dependent processes. It is now known that such changes in synaptic strength induce compensatory regulation at GABAergic synapses to prevent global alterations in network activity. The fast time scale of synapse turnover implies the existence of cellular mechanisms to facilitate rapid building of GABAergic PSDs. Overall, the regulation of the GABAergic PSD has received little attention so far, however, in recent years, there has been considerable advance in the characterization of molecular structure and regulation of the GABAergic postsynaptic density (PSD). The protein identified to play pre-eminent role in this process is a multi-functional scaffolding protein gephyrin, which interacts with numerous signaling molecules and also with a1, a2, and a3 subunit-containing GABAARs. Nevertheless, many aspects governing the formation and plasticity of the GABAergic PSD remain unclear. This seminar will present evidence showing the convergence of signaling pathways that facilitate changes in GABAergic neurotransmission in brain pathology like ischemia