RECRUITMENT OF FUNCTIONAL GABA(A) RECEPTORS TO POSTSYNAPTIC DOMAINS BY INSULIN

Modification of synaptic strength in the mammalian central nervous sys tem (CNS) occurs at both pre- and postsynaptic sites(1,2). However, be cause postsynaptic receptors are likely to be saturated by released tr ansmitter, an increase in the number of active postsynaptic receptors may be a more efficient way of strengthening synaptic efficacy(3-7). B ut there has been no evidence for a rapid recruitment of neurotransmit ter receptors to the postsynaptic membrane in the CNS, Here we report that insulin causes the type A gamma-aminobutyric acid (GABA(A)) recep tor, the principal receptor that mediates synaptic inhibition in the C NS8, to translocate rapidly from the intracellular compartment to the plasma membrane in transfected HEK 293 cells, and that this relocation requires the beta 2 subunit of the GABA(A) receptor. In CNS neurons, insulin increases the expression of GABA(A) receptors on the postsynap tic and dendritic membranes. We found that insulin increases the numbe r of functional postsynaptic GABA(A) receptors, thereby increasing the amplitude of the GABA(A)-receptor-mediated miniature inhibitory posts ynaptic currents (mIPSCs) without altering their time course. These re sults provide evidence for a rapid recruitment of functional receptors to the postsynaptic plasmamembrane, suggesting a fundamental mechanis m for the generation of synaptic plasticity.