Nicotinic ACh receptors in the hippocampal circuit; functional expression and role in synaptic plasticity

Abstract

Acetylcholine (ACh) can regulate neuronal excitability in the hippocampus, an important area in the brain for learning and memory, by acting on both nicotinic (nAChRs) and muscarinic ACh receptors. The primary cholinergic input to the hippocampus arises from the medial septum and diagonal band of Broca (MS-DBB), and we investigated how their activation regulated hippocampal synaptic plasticity. We found that activation of these endogenous cholinergic inputs can directly induce different forms of hippocampal synaptic plasticity with a timing precision in the millisecond range. Furthermore, we observed a prolonged enhancement of excitability both pre- and postsynaptically. Lastly we found that the presence of the α7 nAChR subtype to both pre- and postsynaptic sites appeared to be required to induce this plasticity. We propose that α7 nAChRs coordinate pre- and postsynaptic activities to induce glutamatergic synaptic plasticity, and thus provide a novel mechanism underlying physiological neuronal communication that could lead to timing-dependent synaptic plasticity in the hippocampus.

Figure 1. Both pre- and postsynaptic α7 nAChRs are required for the ACh-induced induction of LTP and STD

The release of glutamate by CA3 pyramidal neurons and the resulting effect on glutamate receptors on the spines of CA1 pyramidal neurons is regulated by endogenous ACh released by septal cholinergic neurons acting on α7 receptors both on the pre- and postsynaptic membranes.