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Science (New York, N.Y.) Dec 2022The primary motor cortex (M1) is involved in the control of voluntary movements and is extensively mapped in this capacity. Although the M1 is implicated in modulation...
The primary motor cortex (M1) is involved in the control of voluntary movements and is extensively mapped in this capacity. Although the M1 is implicated in modulation of pain, the underlying circuitry and causal underpinnings remain elusive. We unexpectedly unraveled a connection from the M1 to the nucleus accumbens reward circuitry through a M1 layer 6-mediodorsal thalamus pathway, which specifically suppresses negative emotional valence and associated coping behaviors in neuropathic pain. By contrast, layer 5 M1 neurons connect with specific cell populations in zona incerta and periaqueductal gray to suppress sensory hypersensitivity without altering pain affect. Thus, the M1 employs distinct, layer-specific pathways to attune sensory and aversive-emotional components of neuropathic pain, which can be exploited for purposes of pain relief.
Topics: Motor Cortex; Neural Pathways; Neuralgia; Neurons; Periaqueductal Gray; Thalamus; Animals; Mice
PubMed: 36548429
DOI: 10.1126/science.add4391 -
Cell Mar 2022Motor behaviors are often planned long before execution but only released after specific sensory events. Planning and execution are each associated with distinct...
Motor behaviors are often planned long before execution but only released after specific sensory events. Planning and execution are each associated with distinct patterns of motor cortex activity. Key questions are how these dynamic activity patterns are generated and how they relate to behavior. Here, we investigate the multi-regional neural circuits that link an auditory "Go cue" and the transition from planning to execution of directional licking. Ascending glutamatergic neurons in the midbrain reticular and pedunculopontine nuclei show short latency and phasic changes in spike rate that are selective for the Go cue. This signal is transmitted via the thalamus to the motor cortex, where it triggers a rapid reorganization of motor cortex state from planning-related activity to a motor command, which in turn drives appropriate movement. Our studies show how midbrain can control cortical dynamics via the thalamus for rapid and precise motor behavior.
Topics: Animals; Mesencephalon; Mice; Motor Cortex; Movement; Neurons; Thalamus
PubMed: 35245431
DOI: 10.1016/j.cell.2022.02.006 -
Nature Oct 2021A mammalian brain is composed of numerous cell types organized in an intricate manner to form functional neural circuits. Single-cell RNA sequencing allows systematic...
A mammalian brain is composed of numerous cell types organized in an intricate manner to form functional neural circuits. Single-cell RNA sequencing allows systematic identification of cell types based on their gene expression profiles and has revealed many distinct cell populations in the brain. Single-cell epigenomic profiling further provides information on gene-regulatory signatures of different cell types. Understanding how different cell types contribute to brain function, however, requires knowledge of their spatial organization and connectivity, which is not preserved in sequencing-based methods that involve cell dissociation. Here we used a single-cell transcriptome-imaging method, multiplexed error-robust fluorescence in situ hybridization (MERFISH), to generate a molecularly defined and spatially resolved cell atlas of the mouse primary motor cortex. We profiled approximately 300,000 cells in the mouse primary motor cortex and its adjacent areas, identified 95 neuronal and non-neuronal cell clusters, and revealed a complex spatial map in which not only excitatory but also most inhibitory neuronal clusters adopted laminar organizations. Intratelencephalic neurons formed a largely continuous gradient along the cortical depth axis, in which the gene expression of individual cells correlated with their cortical depths. Furthermore, we integrated MERFISH with retrograde labelling to probe projection targets of neurons of the mouse primary motor cortex and found that their cortical projections formed a complex network in which individual neuronal clusters project to multiple target regions and individual target regions receive inputs from multiple neuronal clusters.
Topics: Animals; Atlases as Topic; GABAergic Neurons; Gene Expression Profiling; Glutamates; In Situ Hybridization, Fluorescence; Male; Mice; Mice, Inbred C57BL; Motor Cortex; Neurons; Organ Specificity; Single-Cell Analysis; Transcriptome
PubMed: 34616063
DOI: 10.1038/s41586-021-03705-x -
Annual Review of Neuroscience Jul 2022The brain plans and executes volitional movements. The underlying patterns of neural population activity have been explored in the context of movements of the eyes,... (Review)
Review
The brain plans and executes volitional movements. The underlying patterns of neural population activity have been explored in the context of movements of the eyes, limbs, tongue, and head in nonhuman primates and rodents. How do networks of neurons produce the slow neural dynamics that prepare specific movements and the fast dynamics that ultimately initiate these movements? Recent work exploits rapid and calibrated perturbations of neural activity to test specific dynamical systems models that are capable of producing the observed neural activity. These joint experimental and computational studies show that cortical dynamics during motor planning reflect fixed points of neural activity (attractors). Subcortical control signals reshape and move attractors over multiple timescales, causing commitment to specific actions and rapid transitions to movement execution. Experiments in rodents are beginning to reveal how these algorithms are implemented at the level of brain-wide neural circuits.
Topics: Algorithms; Animals; Brain; Motor Cortex; Movement; Neurons
PubMed: 35316610
DOI: 10.1146/annurev-neuro-092021-121730 -
Philosophical Transactions of the Royal... Dec 2021Humans are vocal modulators par excellence. This ability is supported in part by the dual representation of the laryngeal muscles in the motor cortex. Movement, however,... (Review)
Review
Humans are vocal modulators par excellence. This ability is supported in part by the dual representation of the laryngeal muscles in the motor cortex. Movement, however, is not the product of motor cortex alone but of a broader motor network. This network consists of brain regions that contain somatotopic maps that parallel the organization in motor cortex. We therefore present a novel hypothesis that the dual laryngeal representation is repeated throughout the broader motor network. In support of the hypothesis, we review existing literature that demonstrates the existence of network-wide somatotopy and present initial evidence for the hypothesis' plausibility. Understanding how this uniquely human phenotype in motor cortex interacts with broader brain networks is an important step toward understanding how humans evolved the ability to speak. We further suggest that this system may provide a means to study how individual components of the nervous system evolved within the context of neuronal networks. This article is part of the theme issue 'Voice modulation: from origin and mechanism to social impact (Part I)'.
Topics: Brain; Brain Mapping; Larynx; Magnetic Resonance Imaging; Motor Cortex; Movement
PubMed: 34719252
DOI: 10.1098/rstb.2020.0392 -
Nature Communications Aug 2022Anterior cingulate cortex mediates the flexible updating of an animal's choice responses upon rule changes in the environment. However, how anterior cingulate cortex...
Anterior cingulate cortex mediates the flexible updating of an animal's choice responses upon rule changes in the environment. However, how anterior cingulate cortex entrains motor cortex to reorganize rule representations and generate required motor outputs remains unclear. Here, we demonstrate that chemogenetic silencing of the terminal projections of cingulate cortical neurons in secondary motor cortex in the rat disrupts choice performance in trials immediately following rule switches, suggesting that these inputs are necessary to update rule representations for choice decisions stored in the motor cortex. Indeed, the silencing of cingulate cortex decreases rule selectivity of secondary motor cortical neurons. Furthermore, optogenetic silencing of cingulate cortical neurons that is temporally targeted to error trials immediately after rule switches exacerbates errors in the following trials. These results suggest that cingulate cortex monitors behavioral errors and updates rule representations in motor cortex, revealing a critical role for cingulate-motor circuits in adaptive choice behaviors.
Topics: Animals; Gyrus Cinguli; Motor Cortex; Neurons; Rats
PubMed: 35927275
DOI: 10.1038/s41467-022-32142-1 -
International Review of Neurobiology 2021Medial secondary motor cortex (MOs or M2) constitutes the dorsal aspect of the rodent medial frontal cortex. We previously proposed that the function of MOs is to link... (Review)
Review
Medial secondary motor cortex (MOs or M2) constitutes the dorsal aspect of the rodent medial frontal cortex. We previously proposed that the function of MOs is to link antecedent conditions, including sensory stimuli and prior choices, to impending actions. In this review, we focus on the long-range pathways between MOs and other cortical and subcortical regions. We highlight three circuits: (1) connections with visual and auditory cortices that are essential for predictive coding of perceptual inputs; (2) connections with motor cortex and brainstem that are responsible for top-down, context-dependent modulation of movements; (3) connections with retrosplenial cortex, orbitofrontal cortex, and basal ganglia that facilitate reward-based learning. Together, these long-range circuits allow MOs to broadcast choice signals for feedback and to bias decision-making processes.
Topics: Animals; Bias; Decision Making; Motor Cortex
PubMed: 33785155
DOI: 10.1016/bs.irn.2020.11.008 -
ELife Oct 2023Frontal motor areas are central to controlling voluntary movements. In non-human primates, the motor areas contain independent, somatotopic, representations of the...
Frontal motor areas are central to controlling voluntary movements. In non-human primates, the motor areas contain independent, somatotopic, representations of the forelimb (i.e., motor maps). But are the neural codes for actions spatially organized within those forelimb representations? Addressing this question would provide insight into the poorly understood structure-function relationships of the cortical motor system. Here, we tackle the problem using high-resolution optical imaging and motor mapping in motor (M1) and dorsal premotor (PMd) cortex. Two macaque monkeys performed an instructed reach-to-grasp task while cortical activity was recorded with intrinsic signal optical imaging (ISOI). The spatial extent of activity in M1 and PMd was then quantified in relation to the forelimb motor maps, which we obtained from the same hemisphere with intracortical microstimulation. ISOI showed that task-related activity was concentrated in patches that collectively overlapped <40% of the M1 and PMd forelimb representations. The spatial organization of the patches was consistent across task conditions despite small variations in forelimb use. Nevertheless, the largest condition differences in forelimb use were reflected in the magnitude of cortical activity. Distinct time course profiles from patches in arm zones and patches in hand zones suggest functional differences within the forelimb representations. The results collectively support an organizational framework wherein the forelimb representations contain subzones enriched with neurons tuned for specific actions. Thus, the often-overlooked spatial dimension of neural activity appears to be an important organizing feature of the neural code in frontal motor areas.
Topics: Animals; Motor Cortex; Brain Mapping; Macaca; Forelimb; Neurons; Electric Stimulation
PubMed: 37855376
DOI: 10.7554/eLife.83196 -
Proceedings of the National Academy of... May 2022Marmosets display remarkable vocal motor abilities. Macaques do not. What is it about the marmoset brain that enables its skill in the vocal domain? We examined the...
Marmosets display remarkable vocal motor abilities. Macaques do not. What is it about the marmoset brain that enables its skill in the vocal domain? We examined the cortical control of a laryngeal muscle that is essential for vocalization in both species. We found that, in both monkeys, multiple premotor areas in the frontal lobe along with the primary motor cortex (M1) are major sources of disynaptic drive to laryngeal motoneurons. Two of the premotor areas, ventral area 6 (area 6V) and the supplementary motor area (SMA), are a substantially larger source of descending output in marmosets. We propose that the enhanced vocal motor skills of marmosets are due, in part, to the expansion of descending output from these premotor areas.
Topics: Animals; Brain Mapping; Haplorhini; Laryngeal Muscles; Motor Cortex; Vocalization, Animal
PubMed: 35507879
DOI: 10.1073/pnas.2122345119 -
Neuroscience Mar 2022The primary motor cortex, a dynamic center for overall motion control and decision making, undergoes significant alterations upon neural stimulation. Over the last few... (Review)
Review
The primary motor cortex, a dynamic center for overall motion control and decision making, undergoes significant alterations upon neural stimulation. Over the last few decades, data from numerous studies using rodent models have improved our understanding of the morphological and functional plasticity of the primary motor cortex. In particular, spatially specific formation of dendritic spines and their maintenance during distinct behaviors is considered crucial for motor learning. However, whether the modifications of specific synapses are associated with motor learning should be studied further. In this review, we summarized the findings of prior studies on the features and dynamics of the primary motor cortex in rodents.
Topics: Animals; Dendritic Spines; Motor Cortex; Neuronal Plasticity; Rodentia; Synapses
PubMed: 35051529
DOI: 10.1016/j.neuroscience.2022.01.009