GABAERGIC HETEROSYNAPTIC BEHAVIORAL TIMESCALE PLASTICITY IN THE HIPPOCAMPUS

The mechanisms underlying induction of long-term plasticity at inhibitory synapses (iLTP/iLTD) differ from the well-established rules governing excitatory plasticity. A distinctive property of inhibitory plasticity is its heterosynaptic nature, whereby non-stimulated GABAergic synapses undergo modifications in response to activity at nearby excitatory inputs. Here, we examined the mechanisms that promote GABAergic plasticity under behavioral-timescale plasticity (BTSP) paradigm. To this end, we simultaneously recorded, in hippocampal slices, excitatory and optogenetically evoked inhibitory postsynaptic currents in CA1 pyramidal cells (CA1PCs). Excitatory BTSP was induced in the current-clamp mode by pairing burst of 10 stimuli (20Hz) at CA3→CA1PC input with a plateau potential evoked by somatic current injection (300 ms, 500 pA).
We observed statistically significant excitatory LTP after coincident BTSP pairing (Δt=0ms), causal pre→postsynaptic BTSP pairing (Δt=-750ms), and acausal post→presynaptic pairing (Δt=+750ms). Notably, BTSP induction did not elicit heterosynaptic plasticity at inhibitory inputs arising from parvalbumin-expressing interneurons. In contrast, at inhibitory synapses formed by somatostatin-containing interneurons (SST→CA1PC), excitatory BTSP led to the concurrent expression of long-term GABAergic plasticity. Importantly, coincident, causal, and acausal BTSP pairings all produced iLTP at SST→CA1PC synapses. Moreover, whereas the magnitude of excitatory BTSP declined with increasing pairing interval, the associated heterosynaptic inhibitory plasticity remained comparable across the −750ms to +750ms Δt range.
These findings demonstrate that BTSP-associated heterosynaptic GABAergic plasticity is synapse-specific and depends on interneuron subtype, providing a framework for understanding how inhibitory circuits are coordinated with excitatory learning signals during hippocampus-dependent memory formation. Funding: NCN OPUS grants: 2021/43/B/NZ4/01675 and 2021/43/B/NZ4/01675.