Distinct GABAergic modulation of timing-dependent LTP in CA1 pyramidal neurons along the longitudinal axis of the mouse hippocampus

Abstract

Synaptic plasticity in the hippocampus underlies episodic memory formation, with dorsal hippocampus being instrumental for spatial memory whereas ventral hippocampus is crucial for emotional learning. Here, we studied how GABAergic inhibition regulates physiologically relevant low repeat spike timing-dependent LTP (t-LTP) at Schaffer collateral-CA1 synapses along the dorsoventral hippocampal axis. We used two t-LTP protocols relying on only 6 repeats of paired spike-firing in pre- and postsynaptic cells within 10s that differ in postsynaptic firing patterns. GABAA receptor mechanisms played a greater role in blocking 6× 1:1 t-LTP that recruits single postsynaptic action potentials. 6× 1:4 t-LTP that depends on postsynaptic burst-firing unexpectedly required intact GABAB receptor signaling. The magnitude of both t-LTP-forms decreased along the dorsoventral axis, despite increasing excitability and basal synaptic strength in this direction. This suggests that GABAergic inhibition contributes to the distinct roles of dorsal and ventral hippocampus in memory formation.