A Cholinergic Receptor Gene (CHRM2) Affects Event-related Oscillations

Abstract

We report genetic linkage and association findings which implicate the gene encoding the muscarinic acetylcholine receptor M2 (CHRM2) in the modulation of a scalp-recorded electrophysiological phenotype. The P3 (P300) response was evoked using a three-stimulus visual oddball paradigm and a phenotype that relates to the energy in the theta band (4-5 Hz) was analyzed. Studies have shown that similar electrophysiological measures represent cognitive correlates of attention, working memory, and response selection; a role has been suggested for the ascending cholinergic pathway in the same functions. The results of our genetic association tests, combined with knowledge regarding the presence of presynaptic cholinergic M2 autoreceptors in the basal forebrain, indicate that the cognitive processes required by the experiment may in part be mediated by inhibitory neural networks. These findings underscore the utility of electrophysiology and neurogenetics in the understanding of cognitive function and the study of brain-related disorders.

Sensory evoked and event related oscillations in Alzheimer’s disease: a short review

“…In healthy subjects genetics also contributes to brain responses, since the theta band energy seen in P300 experiments is related to cholinergic receptor gene (Jones et al 2006), and human nicotinic receptor gene modulates auditory and visual event related potentials (Espeseth et al 2007).…”

No Association Between Cholinergic Muscarinic Receptor 2 (CHRM2) Genetic Variation and Cognitive Abilities in Three Independent Samples

“…M1 receptor agonists (AF102B, AF150(S) and AF267B-1) which increase synaptic ACh levels are related to improved cognition in various animal Alzheimer's disease models (Fisher et al 2002) and antagonists of presynaptic M2 receptors (which decrease ACh) enhance cognitive ability in rodents and non-human primates (Carey et al 2001). CHRM2 has been shown to be involved in long-term potentiation (Calabresi et al 1998), which is thought to be a fundamental mechanism in learning and memory (Silva 2003), and single nucleotide polymorphisms (SNPs) have been associated with visual evoked brain oscillations suggesting at least a role for CHRM2 in higher mental functioning in humans (Jones et al 2006), although reports that CHRM2 polymorphisms are associated with alcoholism and depression (Comings et al 2002;Edenberg and Foroud 2006;Luo et al 2005;Wang et al 2004) suggest a nonspecific phenotype.…”

Neurophysiological maturation in adolescence – vulnerability and counteracting addiction to alcohol

“…It was confirmed that an increase in amplitude and power of Beta waves presents the features of electrophysiological endophenotype in the form of an increased predisposition for addiction to alcohol. It must also be said that this endophenotype is accompanied by disorders of behaviour, already in childhood, and more frequent use of psychoactive substances in adolescence, and more frequent anti-social behaviours and attitudes [48,49,50,51].…”

“…The scope of these disorders, connected with a decreased P300 amplitude, covers the syndromes of decreased inhibition, abuse of psychoactive substances, distorted and anti-social behaviours, and the Attention Deficit Hyperactivity Disorder (ADHD). In the EEG recordings of individuals addicted to alcohol who are carriers of this gene, the stimulation of cholinergic muscarinic receptors M2 changes the pattern of the recording of slow waves of the delta and theta frequencies, accompanied by the effect of decreased oscillation values induced, which were also considered as endophenotype [49,53].…”