α7 nicotinic acetylcholine receptors induce long-term synaptic enhancement in the dorsal but not ventral hippocampus

Agents that positively modulate the activity of alpha 7nAChRs are used as cognitive enhancers and for the treatment of hippocampus-dependent functional decline. However, it is not known whether the expression and the effects of alpha 7nAChRs apply to the entire longitudinal axis of the hippocampus equally. Given that cholinergic system-involving hippocampal functions are not equally distributed along the hippocampus, we comparatively examined the expression and the effects of alpha 7nAChRs on excitatory synaptic transmission between the dorsal and the ventral hippocampal slices from adult rats. We found that alpha 7nAChRs are equally expressed in the CA1 field of the two segments of the hippocampus. However, activation of alpha 7nAChRs by their highly selective agonist PNU 282987 induced a gradually developing increase in field excitatory postsynaptic potential only in the dorsal hippocampus. This long-term potentiation was not reversed upon application of nonselective nicotinic receptor antagonist mecamylamine, but the induction of potentiation was prevented by prior blockade of alpha 7nAChRs by their antagonist MG 624. In contrast to the long-term synaptic plasticity, we found that alpha 7nAChRs did not modulate short-term synaptic plasticity in either the dorsal or the ventral hippocampus. These results may have implications for the role that alpha 7nAChRs play in specifically modulating functions that depend on the normal function of the dorsal hippocampus. We propose that hippocampal functions that rely on a direct alpha 7 nAChR-mediated persistent enhancement of glutamatergic synaptic transmission are preferably supported by dorsal but not ventral hippocampal synapses. This study shows that activation of alpha 7nAChRs induces long-lasting enhancement of excitatory synaptic transmission in the dorsal but not the ventral CA3-CA1 synapses despite a similar receptor expression in the two segments of the hippocampus.image