Expression of m1-type muscarinic acetylcholine receptors by parvalbumin-immunoreactive neurons in the primary visual cortex: A comparative study of rat, guinea pig, ferret, macaque, and human

ABSTRACT Cholinergic neuromodulation is a candidate mechanism for aspects of arousal and attention in mammals. We have reported previously that cholinergic modulation in the primary visual cortex (V1) of the macaque monkey is strongly targeted toward GABAergic interneurons, and in particular that the vast majority of parvalbumin‐immunoreactive (PV) neurons in macaque V1 express the m1‐type (pirenzepine‐sensitive, Gq‐coupled) muscarinic ACh receptor (m1AChR). In contrast, previous physiological data indicates that PV neurons in rats rarely express pirenzepine‐sensitive muscarinic AChRs. To examine further this apparent species difference in the cholinergic effectors for the primary visual cortex, we have conducted a comparative study of the expression of m1AChRs by PV neurons in V1 of rats, guinea pigs, ferrets, macaques, and humans. We visualize PV‐ and mAChR‐immunoreactive somata by dual‐immunofluorescence confocal microscopy and find that the species differences are profound; the vast majority (>75%) of PV‐ir neurons in macaques, humans, and guinea pigs express m1AChRs. In contrast, in rats only ∼25% of the PV population is immunoreactive for m1AChRs. Our data reveal that while they do so much less frequently than in primates, PV neurons in rats do express Gq‐coupled muscarinic AChRs, which appear to have gone undetected in the previous in vitro studies. Data such as these are critical in determining the species that represent adequate models for the capacity of the cholinergic system to modulate inhibition in the primate cortex. J. Comp. Neurol. 522:986–1003, 2014. © 2013 Wiley Periodicals, Inc. We used quantitative dual‐immunofluorescence microscopy to reveal profound species differences in the extent to which parvalbumin‐immunoreactive (PV‐ir) neurons are targets for cholinergic modulation mediated by muscarinic receptors. In particular, whereas >75% of PV neurons in human or macaque V1 express m1 muscarinic receptors, only ∼25% do so in rat V1.