Presynaptic M1 muscarinic cholinoceptors mediate inhibition of excitatory synaptic transmission in the hippocampus in vitro

Abstract

The effects of the cholinoceptor agonist, carbachol (CCh), were examined in the rat hippocampal slice preparation. Intracellular recordings from CA 1 pyramidal neurones revealed that CCh (1-3/~M) inhibited excitatory postsynaptic responses evoked by stimulation of the Schaffer collateral/commissural pathway while, at the same time, direct excitability was enhanced. Extracellularly, CCh produced a concentrationdependent reduction of the amplitude of the field excitatory postsynaptic potential (field EPSP) recorded in the CAI apical dendritic region. The muscarinic receptor antagonist, pirenzepine, competitively antagonized the effects of CCh on the field EPSP with a pA2 of 7.4. These results confirm earlier reports of a presynaptic inhibitory action of CCh in the hippocampal CAI region and provide strong evidence that this effect is mediated by muscarinic receptors of the Mt subtype.The classification of muscarinic receptors into two broad categories on the basis of their high (M0 and low (M2) affinities for the antagonist, pirenzepine [9], has prompted a number of attempts to establish the subtypes mediating the electrophysiological responses to muscarinic agonists throughout the brain [4-6, 14-16, 19]. In hippocampal CA I pyramidal neurones, both the membrane depolarization and blockade of IAHp induced by carbachol (CCh) have been attributed to an action at M1 receptors, whereas inhibition of the M-current may result from M2 receptor activation [4]. In addition to these postsynaptic effects, muscarinic agonists can also reduce the synaptically-evoked excitation of CA 1 neurones by a presynaptic mechanism [11,18]. Unfortunately, attempts to classify this latter response in terms of receptor subtype have yielded conflicting reports: both M2 [4] and Mi [16] receptors have been implicated. However, since neither of these earlier studies employed formal quantitative pharmacological procedures, conclusions from them must remain tentative. We

Differential Effects of PACAP-38 on Synaptic Responses in Rat Hippocampal CA1 Region

“…Specifically, ACh can induce a long-lasting muscarinic enhancement of EPSPs (Krnjevic et al 1981;Marchi and Raitieri 1989;Blitzer et al 1990;Markram and Segal 1990;Auerbach and Segal 1994) as well as a suppression of the CA1 responses evoked by stimulation of Schaffer collateral-commissural fibers (Krnjevic et al 1981;Krnjevic and Report 1982;Sheridan and Sutor 1990;Auerbach and Segal 1996). As PACAP-38 enhancement is …”

Pharmacology of the putative M4 muscarinic receptor mediating Ca‐current inhibition in neuroblastoma × glioma hybrid (NG 108–15) cells

“…The present data offer a way of resolving this difficulty, since they suggest that M4 receptors could be responsible for the high pirenzepine sensitivity of Ica-block in sympathetic neurones. Likewise, if Ca-current inhibition does indeed contribute to presynaptic inhibition, then the high potency of pirenzepine against muscarinic presynaptic inhibition in the hippocampus (Dutar & Nicol, 1988;Sheridan & Sutor, 1990), olfactory cortex (Williams & Constanti, 1988) and septum (Hasuo et al, 1988) might also reflect involvement of the putative M4 receptor. Other instances of high presynaptic potency of pirenzepine include muscarinic inhibition of sympathetic transmission in rabbit ear artery (Choo et al, .O_ 1986), acetylcholine release in chick heart (Jeck et al, 1988) and sympathetic transmission at rabbit vas deferens (Eltze, 1988).…”

Computational model of carbachol‐induced delta, theta, and gamma oscillations in the hippocampus

“…Experimental data for CA1 show that the strengths of Schaffer collateral synapses are reduced by about 50% at 10 M CCH, whereas the perforant path synapses were affected to a lesser extent (Hasselmo and Schnell, 1994). The strengths of the Schaffer collateral field EPSPs were reduced to an even larger extent (Sheridan and Sutor, 1990). In our model, synaptic strength was taken to be constant for the low and medium carbachol concentrations (CCH Ͻ13 M), and reduced by 50% for high carbachol concentrations (CCH Ͼ13 M).…”