Muscarinic acetylcholine receptors in macaque V1 are most frequently expressed by parvalbumin‐immunoreactive neurons

Abstract

Acetylcholine (ACh) is believed to underlie mechanisms of arousal and attention in mammals. ACh also has a demonstrated functional effect in visual cortex that is both diverse and profound. We have reported previously that cholinergic modulation in V1 of the macaque monkey is strongly targeted toward GABAergic interneurons. Here we examine the localization of m1 and m2 muscarinic receptor subtypes across subpopulations of GABAergic interneurons-identified by their expression of the calcium-binding proteins parvalbumin, calbindin, and calretinin-using dualimmunofluorescence confocal microscopy in V1 of the macaque monkey. In doing so, we find that the vast majority (87%) of parvalbumin-immunoreactive neurons express m1-type muscarinic ACh receptors. m1 receptors are also expressed by 60% of calbindin-immunoreactive neurons and 40% of calretinin-immunoreactive neurons. m2 AChRs, on the other hand, are expressed by only 31% of parvalbumin neurons, 23% of calbindin neurons, and 25% of calretinin neurons. Parvalbuminimmunoreactive cells comprise ≈75% of the inhibitory neuronal population in V1 and included in this large subpopulation are neurons known to veto and regulate the synchrony of principal cell spiking. Through the expression of m1 ACh receptors on nearly all of these PV cells, the cholinergic system avails itself of powerful control of information flow through and processing within the network of principal cells in the cortical circuit. Keywords cholinergic; neuromodulation; GABAergic; striate cortex; immunofluorescence; dual-labeling; calcium-binding proteins; calbindin; calretinin; parvalbumin Acetylcholine (ACh) is a ubiquitous neuromodulator in the mammalian central nervous system and is implicated in many brain processes, including the sleep/wake cycle and arousal (Jasper and Tessier, 1971;Jimenez-Capdeville and Dykes, 1996;Vazquez and Baghdoyan, 2001), reward and addiction (Maskos et al., 2005), attention (Sarter et al., 2005), learning and memory (Everitt and Robbins, 1997;Rezvani and Levin, 2001;Hasselmo and McGaughy, 2004), as well as a number of neuropathologies including Alzheimer's disease (Gallagher and Colombo, 1995). We have previously reported that muscarinic acetylcholine receptors (mAChRs) are expressed by a larger proportion of GABAergic interneurons than non-GABAergic (putatively excitatory) neurons in the primary visual cortex (V1) of the macaque monkey (Disney et al., 2006). However, cortical inhibitory neurons are not a homogeneous population. GABAexpressing neurons display considerable functional diversity, which is reflected in their varying dendritic and axonal morphology and in the cells and cellular compartments their axons target. While anatomical classification of GABAergic neurons has traditionally been based on these NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript morphological characteristics (Lund, 1987;Van Brederode et al., 1990;Lund and Yoshioka, 1991;Meskenaite, 1997;Lund and Wu, 1997; De-Felipe et al., 1999), an alternative classificat...

Cholinergic modulation of response gain in the primary visual cortex of the macaque

“…8B). Consistent with this, mAChR proteins (m1 and m2) have been observed in cells throughout cortical layers in macaque V1 (Disney and Aoki 2008;Disney et al 2006;Mrzljak et al 1993), suggesting that m1-and m2-AChRs play important roles in facilitatory modulation. It remains to be clarified, however, how this facilitatory effect is mediated by mAChRs in the neuronal circuitry of V1.…”

“…8B; n ϭ 47). An antagonistic effect by At was observed across all cortical layers, which is consistent with the expression of mAChR proteins (Disney and Aoki 2008;Disney et al 2006). We estimated laminar differences in the relative contribution of non-mAChRs by calculating their mean percentage contribution in each layer.…”

“…In macaque V1, two groups of AChRs are expressed: muscarinic AChRs (mAChRs), which are G-protein-coupled receptors (Disney and Aoki 2008;Disney et al 2006;Mrzljak et al 1993), and nicotinic AChRs (nAChRs), which are ligand-gated ion channels (Disney et al 2007;Han et al 2003). Recently, Disney et al (2007) examined the effects of nicotine, a nAChR agonist, on visual responses and contrast-response relationships in monkey V1 neurons.…”

Basal forebrain activation enhances between-trial reliability of low-frequency local field potentials (LFP) and spiking activity in tree shrew primary visual cortex (V1)

“…In fact, it has been observed that spiking reliability in the LGN is also enhanced following BF electrical stimulation (Goard and Dan 2009). However, this effect could also be mediated by V1 infragranular layer neurons, which express mAChR (Disney and Aoki 2008;Disney et al 2006) and are the main source of LGN top-down modulatory inputs (Fitzpatrick et al 1994). It thus remains possible that the LGN effects are a consequence and not the cause of V1 reliability modulations following BF stimulation.…”

Muscarinic Receptors: Their Roles in Disorders of the Central Nervous System and Potential as Therapeutic Targets

“…The presynaptic M2 receptors are located on the axons of symmetric synapses, in keeping with their role as autoreceptors [12]. However, M2 receptors are also present in a subset of glutamatergic synapses and GABAergic interneurons [13]; nearly a third of cortical GABAergic neurons express M2 receptors [14].…”