Monoaminergic Modulation of Motor Cortex Function

Abstract

Elaboration of appropriate responses to behavioral situations rests on the ability of selecting appropriate motor outcomes in accordance to specific environmental inputs. To this end, the primary motor cortex (M1) is a key structure for the control of voluntary movements and motor skills learning. Subcortical loops regulate the activity of the motor cortex and thus contribute to the selection of appropriate motor plans. Monoamines are key mediators of arousal, attention and motivation. Their firing pattern enables a direct encoding of different states thus promoting or repressing the selection of actions adapted to the behavioral context. Monoaminergic modulation of motor systems has been extensively studied in subcortical circuits. Despite evidence of converging projections of multiple neurotransmitters systems in the motor cortex pointing to a direct modulation of local circuits, their contribution to the execution and learning of motor skills is still poorly understood. Monoaminergic dysregulation leads to impaired plasticity and motor function in several neurological and psychiatric conditions, thus it is critical to better understand how monoamines modulate neural activity in the motor cortex. This review aims to provide an update of our current understanding on the monoaminergic modulation of the motor cortex with an emphasis on motor skill learning and execution under physiological conditions.

Enhanced availability of serotonin increases activation of unfatigued muscle but exacerbates central fatigue during prolonged sustained contractions

“…Serotonergic innervation is widespread throughout the brain, including the motor cortex where it is recognized to influence various aspects of motor function (Ohno et al . ; Vitrac & Benoit‐Marand, ).…”

“…Therefore, caution should be used when attributing changes in motor output (in vivo) to specific receptor subtypes, or even attributing changes in motor output solely to neurons located in the spinal cord. Serotonergic innervation is widespread throughout the brain, including the motor cortex where it is recognized to influence various aspects of motor function (Ohno et al 2013;Vitrac & Benoit-Marand, 2017). A and B) and F-wave persistence (C and D) were measured following the ingestion of paroxetine and a placebo.…”

Synaptic signals mediated by protons and acid‐sensing ion channels

“…Histamine is a neurotransmitter synthesized by neurons in the tuberomammillary nucleus of the posterior hypothalamus (Sherin, Elmquist, Torrealba, & Saper, 1998). Histamine-containing nerve fibers project to many structures in the brain (Panula & Nuutinen, 2013), and histaminergic circuits regulate numerous physiological functions and behaviors, including sleep-wake activities, circadian and feeding rhythms, learning, and memory (for review see Kohler, da Silva, Benetti, & Bonini, 2011;Vitrac & Benoit-Marand, 2017). It has recently been reported that synthetic hydrophobic monoamines potentiate or inhibit ASIC currents in a subunit-specific manner (Shteinikov et al, 2019;Shteinikov, Korosteleva, Tikhonova, Potapieva, & Tikhonov, 2017).…”

Dopamine D2 receptors modulate intrinsic properties and synaptic transmission of parvalbumin interneurons in the mouse primary motor cortex

“…The neuromodulator dopamine (DA) plays a key role in the ability of neural circuits to 78 adaptively control behaviour (Schultz, 2007;Vitrac and Benoit-Marand, 2017;Berke, 79 2018). Indeed, the DA system plays a major role in motor and cognitive functions 80 through its interactions with several brain regions, and its dysregulation leads to 81 cognitive dysfunction (Duvarci et al, 2018) and pathologies like Parkinson's disease 82 and schizophrenia (Nieoullon, 2002).…”

“…Coming mainly from the ventral tegmental area 86 (VTA) but also from the substantia nigra pars compacta (SNc), they richly innervate 87 the superficial and deep layers of the rodent and primate M1 (Descarries et al, 1987; 88 Lewis et al, 1987;Vitrac et al, 2014;Hosp et al, 2015). However, their functional 89 significance is poorly understood and reports of their effects remain conflicting, 90 presumably because of the in vivo exploration and wide neuronal diversity in M1 91 (Hosp and Luft, 2013;Vitrac et al, 2014;Vitrac and Benoit-Marand, 2017). 92 DA acts via two main classes of receptors, the D1-like (D1R) and the D2-like family 93 (D2R) which differentially modulate adenylyl cyclase (Beaulieu and Gainetdinov, 94 2011).…”