Muscarinic M1, but not M4, receptor antagonism impairs divided attention in male rats

Nicklas, Paige R.; Kiefer, Miranda L.; Whalen, Mikaela A.; Stewart, Maeve T.; Mosura, Deandra E.; Bennett, Elizabeth; Hawley, Wayne R.; McLaughlin, Peter

doi:10.1016/j.pbb.2021.173184

Cited by 3 publications

(1 citation statement)

References 58 publications

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“…It seems likely that muscarinic receptor activation is needed for cue detection and sustained attentional processes, as a non-specific muscarinic receptor antagonist is sufficient to impair attentional performance on a two-choice visual discrimination task in mice [53]. Likewise, M1 receptor antagonism impairs performance on a divided attention task in rats, unlike antagonism of the M4 receptor which did not [54]. Additionally, the M1-positive allosteric modulator TAK-071 has been shown to rescue attentional performance in rats with basal forebrain cholinergic cell loss [55].…”

Section: Muscarinic Receptorsmentioning

confidence: 99%

Modes of Acetylcholine Signaling in the Prefrontal Cortex: Implications for Cholinergic Dysfunction and Disorders

Fecik,

M. Savage

2023

Acetylcholine - Recent Advances and New Perspectives

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The forebrain cholinergic system is an important mediator of arousal, attention, memory, and other cognitive processes. Cholinergic signaling is typically divided into two patterns, tonic signaling, which involves sustained changes in ambient acetylcholine (ACh) tone over seconds to minutes, and phasic signaling, which involves fast changing, spatially specific release of ACh on a millisecond timescale. There is evidence to suggest unique functional roles for both types of signaling in the prefrontal cortex: phasic release of ACh is thought to be necessary for attentional processes, as well as cue detection, while tonic signaling is thought to be involved in regulating global arousal states and has been shown to increase with general cognitive demand. The differences between these two types of signaling may originate from electrophysiological properties of cholinergic cell types, distinct muscarinic and nicotinic receptor utilization and/or expression, and/or differential hydrolysis of ACh by acetylcholinesterase. This review will summarize the current views on the functional role of each type of signaling, while the contributions of ACh receptors, hydrolysis, and basal forebrain anatomy are examined. Additionally, the implications of these factors in ACh signaling will be examined in terms of cholinergic circuit dysfunction that occurs in neurodegenerative diseases.

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Section: Muscarinic Receptorsmentioning

confidence: 99%

Modes of Acetylcholine Signaling in the Prefrontal Cortex: Implications for Cholinergic Dysfunction and Disorders

Fecik,

M. Savage

2023

Acetylcholine - Recent Advances and New Perspectives

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Acute Hypobaric Hypoxia Causes Alterations in Acetylcholine-Mediated Signaling Through Varying Expression of Muscarinic Receptors in the Prefrontal Cortex and Cerebellum of Rats’ Brain

Sharma,

Srivastava,

Dakal

et al. 2024

High Altitude Medicine & Biology

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Current Progress on Central Cholinergic Receptors as Therapeutic Targets for Alzheimer's Disease

Nagori,

Pradhan,

Sharma

et al. 2024

CAR

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Acetylcholine (ACh) is ubiquitously present in the nervous system and has been involved in the regulation of various brain functions. By modulating synaptic transmission and promoting synaptic plasticity, particularly in the hippocampus and cortex, ACh plays a pivotal role in the regulation of learning and memory. These procognitive actions of ACh are mediated by the neuronal muscarinic and nicotinic cholinergic receptors. The impairment of cholinergic transmission leads to cognitive decline associated with aging and dementia. Therefore, the cholinergic system has been of prime focus when concerned with Alzheimer’s disease (AD), the most common cause of dementia. In AD, the extensive destruction of cholinergic neurons occurs by amyloid-β plaques and tau protein-rich neurofibrillary tangles. Amyloid-β also blocks cholinergic receptors and obstructs neuronal signaling. This makes the central cholinergic system an important target for the development of drugs for AD. In fact, centrally acting cholinesterase inhibitors like donepezil and rivastigmine are approved for the treatment of AD, although the outcome is not satisfactory. Therefore, identification of specific subtypes of cholinergic receptors involved in the pathogenesis of AD is essential to develop future drugs. Also, the identification of endogenous rescue mechanisms to the cholinergic system can pave the way for new drug development. In this article, we discussed the neuroanatomy of the central cholinergic system. Further, various subtypes of muscarinic and nicotinic receptors involved in the cognition and pathophysiology of AD are described in detail. The article also reviewed primary neurotransmitters that regulate cognitive processes by modulating basal forebrain cholinergic projection neurons.

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Muscarinic M1, but not M4, receptor antagonism impairs divided attention in male rats

Cited by 3 publications

References 58 publications

Modes of Acetylcholine Signaling in the Prefrontal Cortex: Implications for Cholinergic Dysfunction and Disorders

Modes of Acetylcholine Signaling in the Prefrontal Cortex: Implications for Cholinergic Dysfunction and Disorders

Acute Hypobaric Hypoxia Causes Alterations in Acetylcholine-Mediated Signaling Through Varying Expression of Muscarinic Receptors in the Prefrontal Cortex and Cerebellum of Rats’ Brain

Current Progress on Central Cholinergic Receptors as Therapeutic Targets for Alzheimer's Disease

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