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Trends in Cognitive Sciences Sep 2022Mirror neurons (MNs) were first described in a seminal paper in 1992 as a class of monkey premotor cells discharging during both action execution and observation.... (Review)
Review
Mirror neurons (MNs) were first described in a seminal paper in 1992 as a class of monkey premotor cells discharging during both action execution and observation. Despite their debated origin and function, recent studies in several species, from birds to humans, revealed that beyond MNs properly so called, a variety of cell types distributed among multiple motor, sensory, and emotional brain areas form a 'mirror mechanism' more complex and flexible than originally thought, which has an evolutionarily conserved role in social interaction. Here, we trace the current limits and envisage the future trends of this discovery, showing that it inspired translational research and the development of new neurorehabilitation approaches, and constitutes a point of no return in social and affective neuroscience.
Topics: Brain; Brain Mapping; Humans; Mirror Neurons; Motor Cortex; Psychomotor Performance
PubMed: 35803832
DOI: 10.1016/j.tics.2022.06.003 -
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 -
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 Oct 2021Full-length SMART-seq single-cell RNA sequencing can be used to measure gene expression at isoform resolution, making possible the identification of specific isoform...
Full-length SMART-seq single-cell RNA sequencing can be used to measure gene expression at isoform resolution, making possible the identification of specific isoform markers for different cell types. Used in conjunction with spatial RNA capture and gene-tagging methods, this enables the inference of spatially resolved isoform expression for different cell types. Here, in a comprehensive analysis of 6,160 mouse primary motor cortex cells assayed with SMART-seq, 280,327 cells assayed with MERFISH and 94,162 cells assayed with 10x Genomics sequencing, we find examples of isoform specificity in cell types-including isoform shifts between cell types that are masked in gene-level analysis-as well as examples of transcriptional regulation. Additionally, we show that isoform specificity helps to refine cell types, and that a multi-platform analysis of single-cell transcriptomic data leveraging multiple measurements provides a comprehensive atlas of transcription in the mouse primary motor cortex that improves on the possibilities offered by any single technology.
Topics: Animals; Atlases as Topic; Female; GABAergic Neurons; Gene Expression Profiling; Glutamates; In Situ Hybridization, Fluorescence; Male; Mice; Mice, Inbred C57BL; Motor Cortex; Neurons; Organ Specificity; Sequence Analysis; Single-Cell Analysis; Transcriptome
PubMed: 34616073
DOI: 10.1038/s41586-021-03969-3 -
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 -
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 -
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 -
Current Opinion in Neurobiology Jun 2022A rich literature has documented changes in cortical representations of the body in somatosensory and motor cortex. Recent clinical studies of brain-machine interfaces... (Review)
Review
A rich literature has documented changes in cortical representations of the body in somatosensory and motor cortex. Recent clinical studies of brain-machine interfaces designed to assist paralyzed patients have afforded the opportunity to record from and stimulate human somatosensory, motor, and action-related areas of the posterior parietal cortex. These studies show considerable preserved structure in the cortical somato-motor system. Motor cortex can immediately control assistive devices, stimulation of somatosensory cortex produces sensations in an orderly somatotopic map, and the posterior parietal cortex shows a high-dimensional representation of cognitive action variables. These results are strikingly similar to what would be expected in a healthy subject, demonstrating considerable stability of adult cortex even after severe injury and despite potential plasticity-induced new activations within the same region of cortex. Clinically, these results emphasize the importance of targeting cortical areas for BMI control signals that are consistent with their normal functional role.
Topics: Adult; Brain Mapping; Brain-Computer Interfaces; Humans; Motor Cortex; Parietal Lobe; Somatosensory Cortex
PubMed: 35533644
DOI: 10.1016/j.conb.2022.102547 -
Experimental Brain Research Aug 2020I-waves represent high-frequency (~ 600 Hz) repetitive discharge of corticospinal fibers elicited by single-pulse stimulation of motor cortex. First detected and...
I-waves represent high-frequency (~ 600 Hz) repetitive discharge of corticospinal fibers elicited by single-pulse stimulation of motor cortex. First detected and examined in animal preparations, this multiple discharge can also be recorded in humans from the corticospinal tract with epidural spinal electrodes. The exact underpinning neurophysiology of I-waves is still unclear, but there is converging evidence that they originate at the cortical level through synaptic input from specific excitatory interneuronal circuitries onto corticomotoneuronal cells, controlled by GABAAergic interneurons. In contrast, there is at present no supportive evidence for the alternative hypothesis that I-waves are generated by high-frequency oscillations of the membrane potential of corticomotoneuronal cells upon initial strong depolarization. Understanding I-wave physiology is essential for understanding how TMS activates the motor cortex.
Topics: Animals; Evoked Potentials, Motor; Humans; Interneurons; Membrane Potentials; Motor Cortex; Pyramidal Tracts; Transcranial Magnetic Stimulation
PubMed: 32185405
DOI: 10.1007/s00221-020-05764-4