Integration of inhibitory and excitatory effects of α7 nicotinic acetylcholine receptor activation in the prelimbic cortex regulates network activity and plasticity

NEUROPHARMACOLOGY

卷:105

Article

Udakis, Matthew¹  Wright, Victoria Louise¹  Wonnacott, Susan²  Bailey, Christopher Philip¹ 

[1] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England

[2] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England

关键词: Nicotinic receptors;    Prefrontal cortex;    Prelimbic cortex;    Glutamate;    GABA;    LTP;   

DOI  :  10.1016/j.neuropharm.2016.02.028

来源: Elsevier

【 摘 要 】

Cognitive and attentional processes governed by the prefrontal cortex (PFC) are influenced by cholinergic innervation. Here we have explored the role of alpha 7 nicotinic acetylcholine receptors (nAChRs) as mediators of cholinergic signalling in the dorsomedial (prelimbic) PFC, using mouse brain slice electrophysiology. Activation of alpha 7 nAChRs located on glutamatergic terminals and cell soma of GABAergic interneurons increased excitation and inhibition, respectively, in layer V of the prelimbic cortex. These actions were distinguished by their differential dependence on local acetylcholine (ACh): potentiation of endogenous cholinergic signalling with the positive allosteric modulator, PNU-120596, enhanced spontaneous excitatory events, an effect that was further increased by inhibition of acetylcholinesterase. In contrast, alpha 7 nicotinic modulation of inhibitory signalling required addition of exogenous agonist (PNU-282987) as well as PNU-120596, and was unaffected by acetylcholinesterase inhibition. Thus alpha 7 nAChRs can bi-directionally regulate network activity in the prelimbic cortex, depending on the magnitude and localisation of cholinergic signalling. This bidirectional influence is manifest in dual effects of alpha 7 nAChRs on theta-burst-induced long-term potentiation (LTP) in layer V of the prelimbic cortex. Antagonism of alpha 7 nAChRs significantly decreased LTP implicating a contribution from endogenous ACh, consistent with the ability of local ACh to enhance glutamatergic signalling. Exogenous agonist plus potentiator also decreased LTP, indicative of the influence of this drug combination on inhibitory signalling. Thus alpha 7 nAChRs make a complex contribution to network activity and synaptic plasticity in the prelimbic cortex. (C) 2016 The Authors. Published by Elsevier Ltd.

【 授权许可】

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