Differential expression of muscarinic acetylcholine receptors across excitatory and inhibitory cells in visual cortical areas V1 and V2 of the macaque monkey

Abstract

Cholinergic neuromodulation, a candidate mechanism for aspects of attention, is complex and is not well understood. Because structure constrains function, quantitative anatomy is an invaluable tool for reducing such a challenging problem. Our goal was to determine the extent to which m1 and m2 muscarinic acetylcholine receptors (mAChRs) are expressed by inhibitory vs. excitatory neurons in the early visual cortex. To this end, V1 and V2 of macaque monkeys were immunofluorescently labelled for gamma-aminobutyric acid (GABA) and either m1 or m2 mAChRs. Among the GABA-immunoreactive (ir) neurons, 61% in V1 and 63% in V2 were m1 AChR-ir, whereas 28% in V1 and 43% in V2 were m2 AChR-ir. In V1, both mAChRs were expressed by fewer than 10% of excitatory neurons. However, in V2, the population of mAChR-ir excitatory neurons was at least double that observed in V1. We also examined m1 and m2 AChR immunoreactivity in layers 2 and 3 of area V1 under the electron microscope and found evidence that GABAergic neurons localize mAChRs to the soma, whereas glutamatergic neurons expressed mAChRs more strongly in dendrites. Axon and terminal labelling was generally weak. These data represent the first quantitative anatomical study of m1 and m2 AChR expression in the cortex of any species. In addition, the increased expression in excitatory neurons across the V1/V2 border may provide a neural basis for the observation that attentional effects gain strength up through the visual pathway from area V1 through V2 to V4 and beyond.

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.…”

Contribution of Cholinergic and GABAergic Mechanisms to Direction Tuning, Discriminability, Response Reliability, and Neuronal Rate Correlations in Macaque Middle Temporal Area

“…Cholinergic receptor distribution on different cells varies between V1 and V2 (Disney et al, 2006). Therefore, extrapolation of the role of ACh in V1 to higher cortical areas might be misleading.…”