Nicotinic modulation of cortical circuits

Abstract

The ascending cholinergic neuromodulatory system sends projections throughout cortex and has been shown to play an important role in a number of cognitive functions including arousal, working memory, and attention. However, despite a wealth of behavioral and anatomical data, understanding how cholinergic synapses modulate cortical function has been limited by the inability to selectively activate cholinergic axons. Now, with the development of optogenetic tools and cell-type specific Cre-driver mouse lines, it has become possible to stimulate cholinergic axons from the basal forebrain (BF) and probe cholinergic synapses in the cortex for the first time. Here we review recent work studying the cell-type specificity of nicotinic signaling in the cortex, synaptic mechanisms mediating cholinergic transmission, and the potential functional role of nicotinic modulation.

R-(+) and S-(−) Isomers of Cotinine Augment Cholinergic Responses In Vitro and In Vivo

“…Although it is always a challenge to reconcile data obtained in vitro with results obtained in vivo using very different approaches, results obtained from brain slice experiments are shining a new light on our understanding of the role of nAChRs in brain circuits (Arroyo et al, 2014;Bloem et al, 2014). These studies clearly show that a7 and a4b2 nAChRs are expressed in different layers of the cortex, but that some interneurons express both types of receptors as shown by MLA and DHbE inhibition .…”

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

“…The initial evidence of a modulatory role for a7 nAChRs in synaptic activity was obtained in rat hippocampal CA1 pyramidal neurons by examining spontaneous activity and the effect of stimulation of the Schaffer collaterals (Alkondon et al, 1998(Alkondon et al, , 2000Frazier et al, 1998;Hefft et al, 1999). Figure 3 illustrates the localization and laminar localization of a7 nAChR expression in the cerebral cortex obtained by detailed electrophysiological recordings and pharmacological testing (Poorthuis et al, 2013;Arroyo et al, 2014). The fast and slow activity caused by ACh release observed in different neuronal types indicates that these cells must be expressing different nAChR subtypes that might be colocalized or expressed in distinct subcellular areas such as post-and/or perisynaptically.…”

Lesions of the laterodorsal tegmental nucleus alter the cholinergic innervation and neuropeptide Y expression in the medial prefrontal cortex and nucleus accumbens

“…There is also anatomical evidence for a stronger functional interaction of acetylcholine with NPY than with VIP neurons, since NPY neurons are contacted more frequently by cholinergic afferents than VIP neurons (Cauli et al, 2004). Finally, although interneurons in all cortical layers contain acetylcholine receptors, the distribution of the different subtypes of receptors is not the same for all cortical layers and interneuron types (reviewed in Arroyo et al, 2014;Bloem et al, 2014).…”