Vestibular stimulation enhances hippocampal long-term potentiation via activation of cholinergic septohippocampal cells.

Vestibular stimulation induced acetylcholine release in the hippocampus, and acetylcholine is known to facilitate long-term potentiation (LTP) in the hippocampus. Thus, we hypothesize that vestibular stimulation enhances LTP in CA1 in freely behaving rats, and this enhancement depends on the activation of septohippocampal cholinergic neurons. Field excitatory postsynaptic potentials were recorded in CA1 area of behaving rats following stimulation of the basal dendritic afferents. LTP was induced by a single stimulation train (100 pulses at 200 Hz) during passive whole-body rotation or during awake-immobility. LTP induced during rotation was significantly larger than that induced during immobility. Pretreatment with cholinergic antagonist atropine sulfate (50mg/kg i.p.) abolished the facilitation of LTP during rotation as compared to immobility. Selective lesion of cholinergic cells in the medial septum (MS) with 192 IgG-saporin (0.49 μg in 1.4 μl) also abolished the difference in LTP induced during rotation and immobility, which was found in sham-lesion rats. 192 IgG-saporin lesioned rats, as compared to sham-lesion rats, revealed a depletion of MS cells immunopositive to choline acetyltransferase and paling of acetylcholinesterase staining in the hippocampus, without significant change in the number of parvalbumin-immunopositive cells. We conclude that enhancement of LTP during vestibular stimulation is mediated by the activation of cholinergic septohippocampal cells. This is the first direct evidence that vestibular stimulation facilitates hippocampal synaptic plasticity via a cholinergic input.