GABAB autoreceptors regulate the induction of LTP

Abstract

UNDERSTANDING the mechanisms involved in long-term potenti-ation (LTP) should provide insights into the cellular and molecular basis of learning and memory in vertebrates¹. It has been established that in the CA1 region of the hippocampus the induction of LTP requires the transient activation of the N-methyl-D-aspartate (NMDA) receptor system². During low-frequency transmission, significant activation of this system is prevented by γ-aminobutyric acid (GABA) mediated synaptic inhibition^3,4 which hyperpolarizes neurons into a region where NMDA receptor-operated channels are substantially blocked by Mg²⁺ (refs. 5, 6). But during high-frequency transmission, mechanisms are evoked that provide sufficient depolarization of the postsynaptic membrane to reduce this block⁷ and thereby permit the induction of LTP. We now report that this critical depolarization is enabled because during high-frequency transmission GABA depresses its own release by an action on GABA_B autoreceptors, which permits sufficient NMDA receptor activation for the induction of LTP. These findings demonstrate a role for GABAB receptors in synaptic plasticity.