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.

Muscarinic acetylcholine receptors are expressed by most parvalbumin‐immunoreactive neurons in area MT of the macaque

“…Quantified across 2.67 mm 2 of macaque V1 tissue, spanning all cortical layers, eighty percent (235 of 293 raw, 164 of 205 corrected) of PV neurons express m1 AChRs, a replication of our previously published results (Disney et al. ; Disney and Reynolds ). In the same tissue sections, quantified across 4.02 mm 2 of tissue we find that 75% (218 of 293, 153 of 205 corrected) of PV neurons in area MT express m1 AChRs.…”

“…; Disney et al. ; Disney and Aoki ; Disney and Reynolds ) the qualitative appearance of immunoreactivity for m1 AChRs in the occipital lobe of macaque monkeys is that of a stained cytoplasmic ring around an immunonegative nuclear region (asterisks in Fig. A and B).…”

Convergent Mechanisms Underlying Rapid Antidepressant Action

“…Activation of M1-mAChRs expressed on GABAergic interneurons was shown to result in rapid excitation of interneuron activity and thus reinforcing an inhibitory input to the pyramidal neurons [158–160]. M1-mAChR knockdown specifically in somatostatin positive GABAergic interneurons, but not parvalbumin interneurons or pyramidal neurons, prevents the antidepressant behavioral actions of scopolamine [82].…”

GABA interneurons mediate the rapid antidepressant-like effects of scopolamine

“…M1-AChRs are expressed on both GABAergic interneurons and glutamatergic pyramidal neurons in the mPFC and regulate the activity of both cell types (24)(25)(26).…”

“…Alternatively, scopolamine may act directly on pyramidal neurons to enhance synaptic plasticity and produce antidepressant behavioral responses. Recent studies suggest that the M1-type muscarinic ACh receptor (M1-AChR) subtype may mediate the antidepressant actions of scopolamine (9, 22, 23).M1-AChRs are expressed on both GABAergic interneurons and glutamatergic pyramidal neurons in the mPFC and regulate the activity of both cell types (24)(25)(26).In the present study, we used transgenic mice and viralmediated gene transfer to drive Cre-dependent expression of M1-AChR shRNA in different subtypes of GABA interneurons or glutamate neurons in the mPFC. The results demonstrate that M1-AChR knockdown in GABA interneurons, but not pyramidal neurons, blocks the antidepressant-like response to scopolamine in mouse behavioral models.…”