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Nicotinic modulation of cortical circuits.

Arroyo S, Bennett C, Hestrin S - Front Neural Circuits (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Comparative Medicine, Stanford University School of Medicine Stanford, CA, USA.

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.

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Nicotinic signaling in the cortex. Colored cells represent cell-types known to exhibit nAChR-dependent responses to activation of cholinergic axons; black cells represent cell-types that exhibit nicotinic responses to exogenous application of cholinergic agonists; gray cells represent cell-types that do not express nicotinic receptors. The question mark for L5 pyramidal cells reflects the fact that studies disagree as to whether this cell-type expresses functional nicotinic receptors. Two types of nicotinic signaling are depicted: putative volume transmission targeting non-α7 nAChRs (gradient) and putative classical synapses targeting α7 nAChRs (green symbol with orange border).
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Figure 1: Nicotinic signaling in the cortex. Colored cells represent cell-types known to exhibit nAChR-dependent responses to activation of cholinergic axons; black cells represent cell-types that exhibit nicotinic responses to exogenous application of cholinergic agonists; gray cells represent cell-types that do not express nicotinic receptors. The question mark for L5 pyramidal cells reflects the fact that studies disagree as to whether this cell-type expresses functional nicotinic receptors. Two types of nicotinic signaling are depicted: putative volume transmission targeting non-α7 nAChRs (gradient) and putative classical synapses targeting α7 nAChRs (green symbol with orange border).

Mentions: Several studies applying exogenous cholinergic agonists have demonstrated that only a fraction of cortical cells express functional nAChRs (summarized in Figure 1). In the supragranular layers, nicotinic receptors are expressed exclusively in inhibitory cells, including all L1 interneurons (Christophe et al., 2002; Gulledge et al., 2007) and a heterogeneous subset of L2/3 interneurons that co-express one or more of the following biochemical markers: vasoactive intestinal peptide (VIP), cholecystokinin, calretinin, calbindin, and neuropeptide Y (Porter et al., 1999; Gulledge et al., 2007). However, in two of the most prominent classes of inhibitory cells, parvalbumin (PV)-expressing and somatostatin (SOM)-expressing interneurons, nAChR expression is either absent or sparse (Porter et al., 1999; Gulledge et al., 2007). Interestingly, many if not all nAChR-expressing interneurons also express the ionotropic serotonergic receptor (5HT3, Férézou et al., 2002; Lee et al., 2010). Given that cholinergic cells in the BF and serotonergic cells in the raphe nucleus are both more active during wakefulness than during non-rapid eye movement sleep (Wu et al., 2004; Lee et al., 2005), the cortical targets on which these neuromodulatory systems converge may play a role in producing the pattern of activity associated with wakefulness.


Nicotinic modulation of cortical circuits.

Arroyo S, Bennett C, Hestrin S - Front Neural Circuits (2014)

Nicotinic signaling in the cortex. Colored cells represent cell-types known to exhibit nAChR-dependent responses to activation of cholinergic axons; black cells represent cell-types that exhibit nicotinic responses to exogenous application of cholinergic agonists; gray cells represent cell-types that do not express nicotinic receptors. The question mark for L5 pyramidal cells reflects the fact that studies disagree as to whether this cell-type expresses functional nicotinic receptors. Two types of nicotinic signaling are depicted: putative volume transmission targeting non-α7 nAChRs (gradient) and putative classical synapses targeting α7 nAChRs (green symbol with orange border).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3975109&req=5

Figure 1: Nicotinic signaling in the cortex. Colored cells represent cell-types known to exhibit nAChR-dependent responses to activation of cholinergic axons; black cells represent cell-types that exhibit nicotinic responses to exogenous application of cholinergic agonists; gray cells represent cell-types that do not express nicotinic receptors. The question mark for L5 pyramidal cells reflects the fact that studies disagree as to whether this cell-type expresses functional nicotinic receptors. Two types of nicotinic signaling are depicted: putative volume transmission targeting non-α7 nAChRs (gradient) and putative classical synapses targeting α7 nAChRs (green symbol with orange border).
Mentions: Several studies applying exogenous cholinergic agonists have demonstrated that only a fraction of cortical cells express functional nAChRs (summarized in Figure 1). In the supragranular layers, nicotinic receptors are expressed exclusively in inhibitory cells, including all L1 interneurons (Christophe et al., 2002; Gulledge et al., 2007) and a heterogeneous subset of L2/3 interneurons that co-express one or more of the following biochemical markers: vasoactive intestinal peptide (VIP), cholecystokinin, calretinin, calbindin, and neuropeptide Y (Porter et al., 1999; Gulledge et al., 2007). However, in two of the most prominent classes of inhibitory cells, parvalbumin (PV)-expressing and somatostatin (SOM)-expressing interneurons, nAChR expression is either absent or sparse (Porter et al., 1999; Gulledge et al., 2007). Interestingly, many if not all nAChR-expressing interneurons also express the ionotropic serotonergic receptor (5HT3, Férézou et al., 2002; Lee et al., 2010). Given that cholinergic cells in the BF and serotonergic cells in the raphe nucleus are both more active during wakefulness than during non-rapid eye movement sleep (Wu et al., 2004; Lee et al., 2005), the cortical targets on which these neuromodulatory systems converge may play a role in producing the pattern of activity associated with wakefulness.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Comparative Medicine, Stanford University School of Medicine Stanford, CA, USA.

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.

Show MeSH
Related in: MedlinePlus