Voltage clamp analysis of cholinergic action in the hippocampus

Abstract

A slow muscarinic EPSP, accompanied by an increase in membrane input resistance, can be elicited in hippocampal CA1 pyramidal cells in vitro by electrical stimulation of cholinergic afferents in the slice preparation. Associated with the slow EPSP is a blockade of calcium-activated potassium afterhyperpolarizations (AHPs) (Cole and Nicoll, 1984a). In this study a single-electrode voltage clamp was used to examine the currents affected by activation of muscarinic receptors, using either bath application of carbachol or electrical stimulation of the cholinergic afferents. The 3 main findings of this study are that (1) of the 2 calcium-activated potassium currents (termed IAHP and IC) in hippocampal pyramidal cells, only IAHP is sensitive to carbachol; (2) IAHP is approximately 10-fold more sensitive to carbachol than is another muscarine-sensitive current, IM; and (3) neither blockade of IAHP nor of IM can account for the production of the slow EPSP. Rather, the slow EPSP appears to be generated by the blockade of a nonvoltage-dependent, resting potassium current. We propose that the muscarinic blockade of IAHP, which largely accounts for spike frequency adaptation, is primarily involved in enhancing action potential discharge to depolarizing stimuli, while the slow EPSP acts directly to cause action potential discharge.

Protein kinase C-dependent inhibition of K+ currents in noradrenaline-induced depolarization of smooth muscle of guinea-pig vas deferens

“…For example, cholinergic stimulation caused depolarization due to a decrease in the K¤ leakage conductance in the hippocampus (Madison et al 1987;Benson et al 1988). In neurones dissociated from rat neostriatum, histamine reduced the K¤ leakage currents by activation of both H1 and Hµ receptors (Munakata & Akaike, 1994).…”

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

“…Besides depolarization by blocking potassium conductances [70,71] and disinhibition by suppressing GABA release [72], acetylcholine in the hippocampus may potentiate basal-dendritic LTP by facilitating NMDA receptors and their signaling pathways [73,74]. LTP in hippocampal CA1 is sensitive to NMDA receptor antagonists including open-channel blocker MK-801 [75,76].…”

The effects of cholinergic neuromodulation on neuronal phase-response curves of modeled cortical neurons

“…The effect of cholinergic neuromodulation was modeled by altering the conductance (g leak , from 2×10 −5 to 1.8× 10 −5 S cm −2 ) and reversal potential (E leak , from −60 to −58 mV) of the leak current and the conductance of I KM and I KAHP . Madison et al (1987) showed that in hippocampal pyramidal neurons, these two currents are both cholinergically modulated, albeit with different sensitivities. I KAHP is inhibited by cholinergic modulation at about ten times lower concentrations than I KM (IC 50 =0.3 and 5 μM for carbachol).…”

“…Cholinergic modulation affects a variety of both ionotropic (nicotinic) and metabotropic (muscarinic) receptor targets (Schoebesberger et al 2000). Acetylcholine acting on muscarinic receptors downregulates several slow potassium currents (I KM , I KAHP (Madison et al 1987;McCormick 1993)), and changes the input resistance by down regulating the leak conductance. These currents control cellular excitability and repetitive firing of cortical pyramidal neurons.…”