Input specificity of NMDA-dependent GABAergic plasticity in the hippocampus

<p><span style="font-size:11pt;line-height:107%;font-family:&#39;calibri&#39; , sans-serif">Sensory
experiences and learning induce long-lasting changes in both excitatory and
inhibitory synapses, thereby providing a crucial substrate for memory. However,
the co-tuning of excitatory long-term potentiation (eLTP) or depression (eLTD)
with the simultaneous changes at inhibitory synapses (iLTP/iLTD) remains
unclear. Herein, we investigated the co-expression of NMDA-induced synaptic
plasticity at excitatory and inhibitory synapses in hippocampal CA1 pyramidal
cells (PCs) using a combination of electrophysiological, optogenetic, and
pharmacological approaches. We found that inhibitory inputs from somatostatin
(SST)- and parvalbumin (PV)-positive interneurons onto CA1 PCs display
input-specific long-term plastic changes following transient NMDA receptor
activation. Notably, synapses from SST-positive interneurons consistently
exhibited iLTP, irrespective of the direction of excitatory plasticity, whereas
synapses from PV-positive interneurons predominantly showed iLTP concurrent
with eLTP, rather than eLTD. As neuroplasticity is known to depend on the
extracellular matrix, we tested the impact of metalloproteinases (MMP)
inhibition. MMP3 blockade interfered with GABAergic plasticity for all
inhibitory inputs, whereas MMP9 inhibition selectively blocked eLTP and iLTP in
SST-CA1PC synapses co-occurring with eLTP but not eLTD.  These findings demonstrate
the dissociation of excitatory and inhibitory plasticity co-expression. We propose that these mechanisms of
plasticity co-expression may be involved in maintaining excitation-inhibition
balance and modulating neuronal integration modes.</span></p>