RETROGRADE SIGNALING AT GABA(A)-RECEPTOR SYNAPSES IN THE MAMMALIAN CNS

Recent studies have emphasized the role of signals that travel from a target cell, in a retrograde direction, to cells that synapse on the target and influence their output. While the focus of most research on this topic has been on long-lasting alterations at excitatory synapses, evidence that implicates retrograde transmission in the transient reduction of GABA(A)-receptor-mediated inhibition in hippocampus and cerebellum has begun to accumulate. Brief depolarizations of the postsynaptic principal cells lead to increases in the intracellular concentration of Ca2+, and a reduction in GABA(A)-receptor-mediated responses for 1-2 min. No concomitant reduction in postsynaptic GABA(A)-receptor responsiveness has been detected. Rather, release of GABA from inhibitory-interneuron terminals appears to be reduced. The properties of this 'depolarization-induced suppression of inhibition' might be appropriate for unique physiological roles.