Long-term potentiation in neurogliaform interneurons modulates excitation-inhibition balance in the temporoammonic pathway

Apical dendrites of pyramidal neurons integrate information from higher-order cortex and thalamus, and gate signalling and plasticity at proximal synapses. In the hippocampus, neurogliaform cells and other interneurons located within stratum lacunosum-moleculare (SLM) mediate powerful inhibition of CAI pyramidal neuron distal dendrites. Is the recruitment of such inhibition itself subject to use-dependent plasticity, and if so, what induction rules apply? Here we show that interneurons in mouse SI.N1 exhibit I Iebbian NIVIDA receptor-dependent long-term potentiation (LIP). Such plasticity can be induced by selective optogenetic stimulation of afferents in the temporoammonic pathway from the entorhinal cortex (EC), but not by equivalent stimulation of afferents from the thalamic nucleus reuniens. We further show that theta-burst patterns of afferent firing induces LTP in neuroglialorm interneurons identified using neuron-derived neurotrophic factor (Ndnf)-Cre mice. Theta burstactivity of EC afferents led to an increase in disynaptic feed-forward inhibition, but not monosynaptic excitation, of CAI pyramidal neurons. Activity-dependent synaptic plasticity in SLM interneurons thus alters the excitation-inhibition balance at EC inputs to the apical dendrites of pyramidal neurons, implying a dynamic role for these interneurons in gating C'AI dendritic computations.