Cholinergic Modulation Differs between Basal and Apical Dendritic Excitation of Hippocampal CA1 Pyramidal Cells

Abstract

We hypothesize that endogenous cholinergic modulation of dendritic processing of hippocampal CA1 is layer specific, and it specifically enhances spike output resulting from basal as compared with the apical dendritic excitation. Laminar profiles of evoked field potentials were recorded in the CA1 area of urethane-anesthetized rats using multichannel silicon probes and analyzed as current source density. High-frequency stimulation of the pontis oralis (PnO) attenuated the midapical more than the basal or distal apical dendritic excitatory sink. Population spike (PS) and excitatory sink-PS potentiation resulting from basal dendritic excitation were facilitated, while the PS evoked by apical dendritic stimulation was attenuated by PnO stimulation. Perfusion of cholinergic agonist carbachol onto hippocampal slices in vitro also attenuated the apical more than the basal dendritic excitatory postsynaptic potentials. Excitatory sink attenuation and PS changes after PnO stimulation were blocked by systemic or local scopolamine and by intracerebroventricular (icv) M1 receptor antagonist pirenzepine but not by icv M2 receptor antagonist AFDX-116 or nicotinic antagonists. However, a hippocampal theta rhythm activated by PnO stimulation was blocked by systemic but not by local scopolamine. We conclude that endogenous acetylcholine mediates a stronger presynaptic inhibition of the midapical than basal and distal apical excitation mainly through M1 receptors.

Endogenous Histamine Facilitates Long-Term Potentiation in the Hippocampus during Walking

“…The results below were presented for the negative fEPSP at the stratum oriens electrode, which was directly generated by the basal-dendritic excitatory sink in CA1 (Leung and Peloquin, 2010). Because the basal-dendritic fEPSP manifests a dipole field, similar results on LTP were found for the stratum radiatum electrode (supplemental Fig.…”

“…Combined with our previous demonstration that selective lesion of cholinergic neurons in the medial septum with 192IgG-saporin also abolished the facilitation of LTP by walking (Leung et al, 2003), the most parsimonious model consistent with the literature is that histamine excites cholinergic septohippocampal neurons to increase ACh release in the hippocampus. ACh, in turn, may facilitate basal-dendritic LTP by increasing spiking after basal-dendritic excitation (Leung and Peloquin, 2010) or by enhancing NMDA receptor-mediated current (Markram and Segal, 1992;Marino et al, 1998).…”

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

“…The figures will present only the negative fEPSPs recorded at the alveus/stratum oriens electrode, which was directly generated by a basal dendritic excitatory sink in CA1 [49].…”

M1 and M4 Receptors Modulate Hippocampal Pyramidal Neurons

“…Previous studies have implicated M1 (Kremin et al 2006;Leung and Péloquin 2010;Sheridan and Sutor 1990;Shinoe et al 2005), M2 (Dutar and Nicoll 1988;Segal 1989), and M4 receptors (Shirey et al 2008) as mediating cholinergic suppression of glutamate release. We found that M4 receptors are required for normal cholinergic suppression of synaptic transmission at the Schaffer-collateral synapse.…”

“…Cholinergic suppression of synaptic transmission is mediated by mAChRs, but the available data are inconclusive as to the receptor subtype(s) involved. At the Schaffer-collateral synapse, data exist implicating M1 (Kremin et al 2006;Leung and Péloquin 2010;Sheridan and Sutor 1990;Shinoe et al 2005), M2 (Dutar and Nicoll 1988;Seeger et al 2004;Segal 1989), and M4 (Shirey et al 2008) receptors.…”