RESUMEN
How the neocortex modulates hindbrain and spinal circuits is of fundamental interest for understanding motor control and adaptive behaviors. New work from Yang, Kanodia, and Arber demonstrates that there is an exquisite anatomical organization and functional modulation from the anterior (motor) cortex on downstream medulla populations during forelimb behaviors in mice.
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Miembro Anterior , Neocórtex , Animales , Ratones , Corteza Motora/fisiología , Rombencéfalo/fisiología , Columna Vertebral/fisiologíaRESUMEN
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.
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Corteza Motora , Movimiento , Tálamo , Animales , Mesencéfalo , Ratones , Corteza Motora/fisiología , Neuronas/fisiología , Tálamo/fisiologíaRESUMEN
Neural activity underlying short-term memory is maintained by interconnected networks of brain regions. It remains unknown how brain regions interact to maintain persistent activity while exhibiting robustness to corrupt information in parts of the network. We simultaneously measured activity in large neuronal populations across mouse frontal hemispheres to probe interactions between brain regions. Activity across hemispheres was coordinated to maintain coherent short-term memory. Across mice, we uncovered individual variability in the organization of frontal cortical networks. A modular organization was required for the robustness of persistent activity to perturbations: each hemisphere retained persistent activity during perturbations of the other hemisphere, thus preventing local perturbations from spreading. A dynamic gating mechanism allowed hemispheres to coordinate coherent information while gating out corrupt information. Our results show that robust short-term memory is mediated by redundant modular representations across brain regions. Redundant modular representations naturally emerge in neural network models that learned robust dynamics.
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Lóbulo Frontal/fisiología , Red Nerviosa/fisiología , Envejecimiento/fisiología , Animales , Conducta Animal , Cerebro/fisiología , Conducta de Elección , Femenino , Luz , Masculino , Ratones , Modelos Neurológicos , Corteza Motora/fisiología , Neuronas/fisiologíaRESUMEN
Electrical stimulation is a promising tool for modulating brain networks. However, it is unclear how stimulation interacts with neural patterns underlying behavior. Specifically, how might external stimulation that is not sensitive to the state of ongoing neural dynamics reliably augment neural processing and improve function? Here, we tested how low-frequency epidural alternating current stimulation (ACS) in non-human primates recovering from stroke interacted with task-related activity in perilesional cortex and affected grasping. We found that ACS increased co-firing within task-related ensembles and improved dexterity. Using a neural network model, we found that simulated ACS drove ensemble co-firing and enhanced propagation of neural activity through parts of the network with impaired connectivity, suggesting a mechanism to link increased co-firing to enhanced dexterity. Together, our results demonstrate that ACS restores neural processing in impaired networks and improves dexterity following stroke. More broadly, these results demonstrate approaches to optimize stimulation to target neural dynamics.
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Potenciales de Acción/fisiología , Accidente Cerebrovascular/fisiopatología , Animales , Conducta Animal/fisiología , Fenómenos Biomecánicos/fisiología , Estimulación Eléctrica , Haplorrinos , Corteza Motora/fisiopatología , Redes Neurales de la Computación , Neuronas/fisiología , Análisis y Desempeño de Tareas , Factores de TiempoRESUMEN
Decades after the motor homunculus was first proposed, it is still unknown how different body parts are intermixed and interrelated in human motor cortical areas at single-neuron resolution. Using multi-unit recordings, we studied how face, head, arm, and leg movements are represented in the hand knob area of premotor cortex (precentral gyrus) in people with tetraplegia. Contrary to traditional expectations, we found strong representation of all movements and a partially "compositional" neural code that linked together all four limbs. The code consisted of (1) a limb-coding component representing the limb to be moved and (2) a movement-coding component where analogous movements from each limb (e.g., hand grasp and toe curl) were represented similarly. Compositional coding might facilitate skill transfer across limbs, and it provides a useful framework for thinking about how the motor system constructs movement. Finally, we leveraged these results to create a whole-body intracortical brain-computer interface that spreads targets across all limbs.
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Lóbulo Frontal/fisiología , Corteza Motora/anatomía & histología , Corteza Motora/fisiología , Adulto , Mapeo Encefálico , Lóbulo Frontal/anatomía & histología , Cuerpo Humano , Humanos , Corteza Motora/metabolismo , Movimiento/fisiologíaRESUMEN
Sequential activation of neurons has been observed during various behavioral and cognitive processes, but the underlying circuit mechanisms remain poorly understood. Here, we investigate premotor sequences in HVC (proper name) of the adult zebra finch forebrain that are central to the performance of the temporally precise courtship song. We use high-density silicon probes to measure song-related population activity, and we compare these observations with predictions from a range of network models. Our results support a circuit architecture in which heterogeneous delays between sequentially active neurons shape the spatiotemporal patterns of HVC premotor neuron activity. We gauge the impact of several delay sources, and we find the primary contributor to be slow conduction through axonal collaterals within HVC, which typically adds between 1 and 7.5 ms for each link within the sequence. Thus, local axonal "delay lines" can play an important role in determining the dynamical repertoire of neural circuits.
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Pinzones/fisiología , Prosencéfalo/fisiología , Vocalización Animal/fisiología , Comunicación Animal , Animales , Axones , Masculino , Corteza Motora/fisiología , Red Nerviosa/fisiología , Vías Nerviosas/fisiología , Neuronas/fisiologíaRESUMEN
Paralyzed muscles can be reanimated following spinal cord injury (SCI) using a brain-computer interface (BCI) to enhance motor function alone. Importantly, the sense of touch is a key component of motor function. Here, we demonstrate that a human participant with a clinically complete SCI can use a BCI to simultaneously reanimate both motor function and the sense of touch, leveraging residual touch signaling from his own hand. In the primary motor cortex (M1), residual subperceptual hand touch signals are simultaneously demultiplexed from ongoing efferent motor intention, enabling intracortically controlled closed-loop sensory feedback. Using the closed-loop demultiplexing BCI almost fully restored the ability to detect object touch and significantly improved several sensorimotor functions. Afferent grip-intensity levels are also decoded from M1, enabling grip reanimation regulated by touch signaling. These results demonstrate that subperceptual neural signals can be decoded from the cortex and transformed into conscious perception, significantly augmenting function.
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Retroalimentación Sensorial/fisiología , Percepción del Tacto/fisiología , Tacto/fisiología , Adulto , Interfaces Cerebro-Computador/psicología , Mano/fisiopatología , Fuerza de la Mano/fisiología , Humanos , Masculino , Corteza Motora/fisiología , Movimiento/fisiología , Traumatismos de la Médula Espinal/fisiopatologíaRESUMEN
Neurons in the cerebral cortex connect through descending pathways to hindbrain and spinal cord to activate muscle and generate movement. Although components of this pathway have been previously generated and studied in vitro, the assembly of this multi-synaptic circuit has not yet been achieved with human cells. Here, we derive organoids resembling the cerebral cortex or the hindbrain/spinal cord and assemble them with human skeletal muscle spheroids to generate 3D cortico-motor assembloids. Using rabies tracing, calcium imaging, and patch-clamp recordings, we show that corticofugal neurons project and connect with spinal spheroids, while spinal-derived motor neurons connect with muscle. Glutamate uncaging or optogenetic stimulation of cortical spheroids triggers robust contraction of 3D muscle, and assembloids are morphologically and functionally intact for up to 10 weeks post-fusion. Together, this system highlights the remarkable self-assembly capacity of 3D cultures to form functional circuits that could be used to understand development and disease.
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Corteza Cerebral/fisiología , Corteza Motora/fisiología , Organoides/fisiología , Animales , Calcio/metabolismo , Diferenciación Celular , Células Cultivadas , Vértebras Cervicales , Regulación de la Expresión Génica , Glutamatos/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/citología , Ratones , Músculos/fisiología , Mioblastos/metabolismo , Red Nerviosa/fisiología , Optogenética , Organoides/ultraestructura , Rombencéfalo/fisiología , Esferoides Celulares/citología , Médula Espinal/citologíaRESUMEN
We tested a newly described molecular memory system, CCR5 signaling, for its role in recovery after stroke and traumatic brain injury (TBI). CCR5 is uniquely expressed in cortical neurons after stroke. Post-stroke neuronal knockdown of CCR5 in pre-motor cortex leads to early recovery of motor control. Recovery is associated with preservation of dendritic spines, new patterns of cortical projections to contralateral pre-motor cortex, and upregulation of CREB and DLK signaling. Administration of a clinically utilized FDA-approved CCR5 antagonist, devised for HIV treatment, produces similar effects on motor recovery post stroke and cognitive decline post TBI. Finally, in a large clinical cohort of stroke patients, carriers for a naturally occurring loss-of-function mutation in CCR5 (CCR5-Δ32) exhibited greater recovery of neurological impairments and cognitive function. In summary, CCR5 is a translational target for neural repair in stroke and TBI and the first reported gene associated with enhanced recovery in human stroke.
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Lesiones Traumáticas del Encéfalo/terapia , Receptores CCR5/metabolismo , Accidente Cerebrovascular/terapia , Anciano , Anciano de 80 o más Años , Animales , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Espinas Dendríticas/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Corteza Motora/metabolismo , Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Receptores CCR5/fisiología , Rehabilitación de Accidente Cerebrovascular/métodosRESUMEN
In speech, the highly flexible modulation of vocal pitch creates intonation patterns that speakers use to convey linguistic meaning. This human ability is unique among primates. Here, we used high-density cortical recordings directly from the human brain to determine the encoding of vocal pitch during natural speech. We found neural populations in bilateral dorsal laryngeal motor cortex (dLMC) that selectively encoded produced pitch but not non-laryngeal articulatory movements. This neural population controlled short pitch accents to express prosodic emphasis on a word in a sentence. Other larynx cortical representations controlling voicing and longer pitch phrase contours were found at separate sites. dLMC sites also encoded vocal pitch during a non-speech singing task. Finally, direct focal stimulation of dLMC evoked laryngeal movements and involuntary vocalization, confirming its causal role in feedforward control. Together, these results reveal the neural basis for the voluntary control of vocal pitch in human speech. VIDEO ABSTRACT.
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Laringe/fisiología , Corteza Motora/fisiología , Habla , Adolescente , Adulto , Mapeo Encefálico , Electrocorticografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Adulto JovenRESUMEN
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.
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Corteza Motora , Algoritmos , Animales , Encéfalo/fisiología , Corteza Motora/fisiología , Movimiento/fisiología , Neuronas/fisiologíaRESUMEN
Animals have exquisite control of their bodies, allowing them to perform a diverse range of behaviours. How such control is implemented by the brain, however, remains unclear. Advancing our understanding requires models that can relate principles of control to the structure of neural activity in behaving animals. Here, to facilitate this, we built a 'virtual rodent', in which an artificial neural network actuates a biomechanically realistic model of the rat1 in a physics simulator2. We used deep reinforcement learning3-5 to train the virtual agent to imitate the behaviour of freely moving rats, thus allowing us to compare neural activity recorded in real rats to the network activity of a virtual rodent mimicking their behaviour. We found that neural activity in the sensorimotor striatum and motor cortex was better predicted by the virtual rodent's network activity than by any features of the real rat's movements, consistent with both regions implementing inverse dynamics6. Furthermore, the network's latent variability predicted the structure of neural variability across behaviours and afforded robustness in a way consistent with the minimal intervention principle of optimal feedback control7. These results demonstrate how physical simulation of biomechanically realistic virtual animals can help interpret the structure of neural activity across behaviour and relate it to theoretical principles of motor control.
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Conducta Animal , Modelos Neurológicos , Redes Neurales de la Computación , Realidad Virtual , Animales , Ratas , Conducta Animal/fisiología , Aprendizaje Profundo , Corteza Motora/fisiología , Movimiento/fisiología , Corteza Sensoriomotora/fisiología , Femenino , Ratas Long-EvansRESUMEN
Working memory, the process through which information is transiently maintained and manipulated over a brief period, is essential for most cognitive functions1-4. However, the mechanisms underlying the generation and evolution of working-memory neuronal representations at the population level over long timescales remain unclear. Here, to identify these mechanisms, we trained head-fixed mice to perform an olfactory delayed-association task in which the mice made decisions depending on the sequential identity of two odours separated by a 5 s delay. Optogenetic inhibition of secondary motor neurons during the late-delay and choice epochs strongly impaired the task performance of the mice. Mesoscopic calcium imaging of large neuronal populations of the secondary motor cortex (M2), retrosplenial cortex (RSA) and primary motor cortex (M1) showed that many late-delay-epoch-selective neurons emerged in M2 as the mice learned the task. Working-memory late-delay decoding accuracy substantially improved in the M2, but not in the M1 or RSA, as the mice became experts. During the early expert phase, working-memory representations during the late-delay epoch drifted across days, while the stimulus and choice representations stabilized. In contrast to single-plane layer 2/3 (L2/3) imaging, simultaneous volumetric calcium imaging of up to 73,307 M2 neurons, which included superficial L5 neurons, also revealed stabilization of late-delay working-memory representations with continued practice. Thus, delay- and choice-related activities that are essential for working-memory performance drift during learning and stabilize only after several days of expert performance.
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Consolidación de la Memoria , Memoria a Corto Plazo , Práctica Psicológica , Animales , Femenino , Masculino , Ratones , Calcio/metabolismo , Conducta de Elección/fisiología , Consolidación de la Memoria/fisiología , Memoria a Corto Plazo/fisiología , Ratones Endogámicos C57BL , Corteza Motora/fisiología , Corteza Motora/citología , Neuronas Motoras/fisiología , Odorantes/análisis , Optogenética , Desempeño Psicomotor/fisiología , Olfato/fisiología , Factores de TiempoRESUMEN
Frontotemporal lobar degeneration (FTLD) causes frontotemporal dementia (FTD), the most common form of dementia after Alzheimer's disease, and is often also associated with motor disorders1. The pathological hallmarks of FTLD are neuronal inclusions of specific, abnormally assembled proteins2. In the majority of cases the inclusions contain amyloid filament assemblies of TAR DNA-binding protein 43 (TDP-43) or tau, with distinct filament structures characterizing different FTLD subtypes3,4. The presence of amyloid filaments and their identities and structures in the remaining approximately 10% of FTLD cases are unknown but are widely believed to be composed of the protein fused in sarcoma (FUS, also known as translocated in liposarcoma). As such, these cases are commonly referred to as FTLD-FUS. Here we used cryogenic electron microscopy (cryo-EM) to determine the structures of amyloid filaments extracted from the prefrontal and temporal cortices of four individuals with FTLD-FUS. Surprisingly, we found abundant amyloid filaments of the FUS homologue TATA-binding protein-associated factor 15 (TAF15, also known as TATA-binding protein-associated factor 2N) rather than of FUS itself. The filament fold is formed from residues 7-99 in the low-complexity domain (LCD) of TAF15 and was identical between individuals. Furthermore, we found TAF15 filaments with the same fold in the motor cortex and brainstem of two of the individuals, both showing upper and lower motor neuron pathology. The formation of TAF15 amyloid filaments with a characteristic fold in FTLD establishes TAF15 proteinopathy in neurodegenerative disease. The structure of TAF15 amyloid filaments provides a basis for the development of model systems of neurodegenerative disease, as well as for the design of diagnostic and therapeutic tools targeting TAF15 proteinopathy.
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Degeneración Lobar Frontotemporal , Factores Asociados con la Proteína de Unión a TATA , Humanos , Amiloide/química , Amiloide/metabolismo , Amiloide/ultraestructura , Tronco Encefálico/metabolismo , Tronco Encefálico/patología , Microscopía por Crioelectrón , Demencia Frontotemporal/etiología , Demencia Frontotemporal/metabolismo , Demencia Frontotemporal/patología , Degeneración Lobar Frontotemporal/complicaciones , Degeneración Lobar Frontotemporal/metabolismo , Degeneración Lobar Frontotemporal/patología , Corteza Motora/metabolismo , Corteza Motora/patología , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Factores Asociados con la Proteína de Unión a TATA/química , Factores Asociados con la Proteína de Unión a TATA/metabolismo , Factores Asociados con la Proteína de Unión a TATA/ultraestructura , Lóbulo Temporal/metabolismo , Lóbulo Temporal/patologíaRESUMEN
What changes in neural architecture account for the emergence and expansion of dexterity in primates? Dexterity, or skill in performing motor tasks, depends on the ability to generate highly fractionated patterns of muscle activity. It also involves the spatiotemporal coordination of activity in proximal and distal muscles across multiple joints. Many motor skills require the generation of complex movement sequences that are only acquired and refined through extensive practice. Improvements in dexterity have enabled primates to manufacture and use tools and humans to engage in skilled motor behaviors such as typing, dance, musical performance, and sports. Our analysis leads to the following synthesis: The neural substrate that endows primates with their enhanced motor capabilities is due, in part, to (a) major organizational changes in the primary motor cortex and (b) the proliferation of output pathways from other areas of the cerebral cortex, especially from the motor areas on the medial wall of the hemisphere.
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Corteza Motora , Animales , Destreza Motora , MovimientoRESUMEN
The study of the cortical control of movement experienced a conceptual shift over recent decades, as the basic currency of understanding shifted from single-neuron tuning towards population-level factors and their dynamics. This transition was informed by a maturing understanding of recurrent networks, where mechanism is often characterized in terms of population-level factors. By estimating factors from data, experimenters could test network-inspired hypotheses. Central to such hypotheses are 'output-null' factors that do not directly drive motor outputs yet are essential to the overall computation. In this Review, we highlight how the hypothesis of output-null factors was motivated by the venerable observation that motor-cortex neurons are active during movement preparation, well before movement begins. We discuss how output-null factors then became similarly central to understanding neural activity during movement. We discuss how this conceptual framework provided key analysis tools, making it possible for experimenters to address long-standing questions regarding motor control. We highlight an intriguing trend: as experimental and theoretical discoveries accumulate, the range of computational roles hypothesized to be subserved by output-null factors continues to expand.
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Corteza Motora , Humanos , Corteza Motora/fisiología , Movimiento/fisiología , Neuronas/fisiologíaRESUMEN
Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations1,2, despite evidence for concentric functional zones3 and maps of complex actions4. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action5 and physiological control6, arousal7, errors8 and pain9. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions4 and connectivity to internal organs10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.
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Mapeo Encefálico , Cognición , Corteza Motora , Mapeo Encefálico/métodos , Mano/fisiología , Imagen por Resonancia Magnética , Corteza Motora/anatomía & histología , Corteza Motora/fisiología , Humanos , Recién Nacido , Lactante , Niño , Animales , Macaca/anatomía & histología , Macaca/fisiología , Pie/fisiología , Boca/fisiología , Conjuntos de Datos como AsuntoRESUMEN
Animals of the same species exhibit similar behaviours that are advantageously adapted to their body and environment. These behaviours are shaped at the species level by selection pressures over evolutionary timescales. Yet, it remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of each individual. The overall organization of neural circuits is preserved across individuals1 because of their common evolutionarily specified developmental programme2-4. Such organization at the circuit level may constrain neural activity5-8, leading to low-dimensional latent dynamics across the neural population9-11. Accordingly, here we suggested that the shared circuit-level constraints within a species would lead to suitably preserved latent dynamics across individuals. We analysed recordings of neural populations from monkey and mouse motor cortex to demonstrate that neural dynamics in individuals from the same species are surprisingly preserved when they perform similar behaviour. Neural population dynamics were also preserved when animals consciously planned future movements without overt behaviour12 and enabled the decoding of planned and ongoing movement across different individuals. Furthermore, we found that preserved neural dynamics extend beyond cortical regions to the dorsal striatum, an evolutionarily older structure13,14. Finally, we used neural network models to demonstrate that behavioural similarity is necessary but not sufficient for this preservation. We posit that these emergent dynamics result from evolutionary constraints on brain development and thus reflect fundamental properties of the neural basis of behaviour.
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Evolución Biológica , Haplorrinos , Corteza Motora , Destreza Motora , Neuronas , Animales , Ratones , Haplorrinos/fisiología , Haplorrinos/psicología , Corteza Motora/citología , Corteza Motora/fisiología , Destreza Motora/fisiología , Movimiento/fisiología , Redes Neurales de la Computación , Neuronas/fisiología , Pensamiento/fisiologíaRESUMEN
Systems consolidation-a process for long-term memory stabilization-has been hypothesized to occur in two stages1-4. Whereas new memories require the hippocampus5-9, they become integrated into cortical networks over time10-12, making them independent of the hippocampus. How hippocampal-cortical dialogue precisely evolves during this and how cortical representations change in concert is unknown. Here, we use a skill learning task13,14 to monitor the dynamics of cross-area coupling during non-rapid eye movement sleep along with changes in primary motor cortex (M1) representational stability. Our results indicate that precise cross-area coupling between hippocampus, prefrontal cortex and M1 can demarcate two distinct stages of processing. We specifically find that each animal demonstrates a sharp increase in prefrontal cortex and M1 sleep slow oscillation coupling with stabilization of performance. This sharp increase then predicts a drop in hippocampal sharp-wave ripple (SWR)-M1 slow oscillation coupling-suggesting feedback to inform hippocampal disengagement and transition to a second stage. Notably, the first stage shows significant increases in hippocampal SWR-M1 slow oscillation coupling in the post-training sleep and is closely associated with rapid learning and variability of the M1 low-dimensional manifold. Strikingly, even after consolidation, inducing new manifold exploration by changing task parameters re-engages hippocampal-M1 coupling. We thus find evidence for dynamic hippocampal-cortical dialogue associated with manifold exploration during learning and adaptation.
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Hipocampo , Aprendizaje , Corteza Motora , Animales , Hipocampo/fisiología , Aprendizaje/fisiología , Consolidación de la Memoria , Memoria a Largo Plazo , Corteza Motora/fisiología , Fases del Sueño/fisiología , Corteza Prefrontal/fisiologíaRESUMEN
While motor cortical circuits contain information related to specific movement parameters1, long-range inputs also have a critical role in action execution2,3. Thalamic projections can shape premotor activity2-6 and have been suggested7 to mediate the selection of short, stereotyped actions comprising more complex behaviours8. However, the mechanisms by which thalamus interacts with motor cortical circuits to execute such movement sequences remain unknown. Here we find that thalamic drive engages a specific subpopulation of premotor neurons within the zebra finch song nucleus HVC (proper name) and that these inputs are critical for the progression between vocal motor elements (that is, 'syllables'). In vivo two-photon imaging of thalamic axons in HVC showed robust song-related activity, and online perturbations of thalamic function caused song to be truncated at syllable boundaries. We used thalamic stimulation to identify a sparse set of thalamically driven neurons within HVC, representing ~15% of the premotor neurons within that network. Unexpectedly, this population of putative thalamorecipient neurons is robustly active immediately preceding syllable onset, leading to the possibility that thalamic input can initiate individual song components through selectively targeting these 'starter cells'. Our findings highlight the motor thalamus as a director of cortical dynamics in the context of an ethologically relevant behavioural sequence.