Nicotinic receptor activation induces NMDA receptor independent long-term potentiation of glutamatergic signalling in hippocampal oriens interneurons.

Many interneurons located in stratum oriens of the rodent hippocampus exhibit a form of long-term potentiation (LTP) of glutamatergic transmission that does not depend on NMDA receptors for its induction but, instead, requires Ca2+ -permeable AMPA receptors and group I metabotropic glutamate receptors. A role for cholinergic signalling has also been reported. However, electrical stimulation of presynaptic axons, conventionally used to evoke synaptic responses, does not allow the relative roles of glutamatergic and cholinergic synapses in the induction of LTP to be distinguished. Here, we show that repetitive optogenetic stimulation confined to cholinergic axons is sufficient to trigger a lasting potentiation of glutamatergic signalling. This phenomenon shows partial occlusion with LTP induced by electrical stimulation, and is sensitive to postsynaptic Ca2+ chelation and blockers of nicotinic receptors. ACh release from cholinergic axons is thus sufficient to trigger heterosynaptic potentiation of glutamatergic signalling to oriens interneurons in the hippocampus.