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Fluorescent genetically encoded voltage indicators report transmembrane potentials of targeted cell-types. However, voltage-imaging instrumentation has lacked the sensitivity to track spontaneous or evoked high-frequency voltage oscillations in neural populations. Here we describe two complementary TEMPO voltage-sensing technologies that capture neural oscillations up to ~100 Hz. Fiber-optic TEMPO achieves ~10-fold greater sensitivity than prior photometry systems, allows hour-long recordings, and monitors two neuron-classes per fiber-optic probe in freely moving mice. With it, we uncovered cross-frequency-coupled theta- and gamma-range oscillations and characterized excitatory-inhibitory neural dynamics during hippocampal ripples and visual cortical processing. The TEMPO mesoscope images voltage activity in two cell-classes across a ~8-mm-wide field-of-view in head-fixed animals. In awake mice, it revealed sensory-evoked excitatory-inhibitory neural interactions and traveling gamma and 3-7 Hz waves in the visual cortex, and previously unreported propagation directions for hippocampal theta and beta waves. These technologies have widespread applications probing diverse oscillations and neuron-type interactions in healthy and diseased brains.
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Placebo effects are notable demonstrations of mind-body interactions1,2. During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain-a phenomenon known as placebo analgesia3-6. However, despite the strength of placebo effects and their impact on everyday human experience and the failure of clinical trials for new therapeutics7, the neural circuit basis of placebo effects has remained unclear. Here we show that analgesia from the expectation of pain relief is mediated by rostral anterior cingulate cortex (rACC) neurons that project to the pontine nucleus (rACCâPn)-a precerebellar nucleus with no established function in pain. We created a behavioural assay that generates placebo-like anticipatory pain relief in mice. In vivo calcium imaging of neural activity and electrophysiological recordings in brain slices showed that expectations of pain relief boost the activity of rACCâPn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an abundance of opioid receptors, further suggesting a role in pain modulation. Inhibition of the rACCâPn pathway disrupted placebo analgesia and decreased pain thresholds, whereas activation elicited analgesia in the absence of placebo conditioning. Finally, Purkinje cells exhibited activity patterns resembling those of rACCâPn neurons during pain-relief expectation, providing cellular-level evidence for a role of the cerebellum in cognitive pain modulation. These findings open the possibility of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain.
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In dynamic environments, animals make behavioral decisions based on the innate valences of sensory cues and information learnt about these cues across multiple timescales1-3. However, it remains unclear how the innate valence of a sensory stimulus affects acquisition of learnt valence information and subsequent memory dynamics. Here we show that in the Drosophila brain, interconnected short- and long-term memory units of the mushroom body jointly regulate memory via dopamine signals that encode innate and learnt sensory valences. Through time-lapse, in vivo voltage-imaging studies of neural spiking in >500 flies undergoing olfactory associative conditioning, we found that protocerebral posterior lateral 1 dopamine neurons (PPL1-DANs)4 heterogeneously and bi-directionally encode innate and learnt valences of punishment, reward, and odor cues. During learning, these valence signals regulate memory storage and extinction in mushroom body output neurons (MBONs)5. In initial conditioning bouts, PPL1-γ1pedc and PPL1-γ2α'1 neurons control short-term memory formation, which weakens inhibitory feedback from MBON-γ1pedc>α/ß to PPL1-α'2α2 and PPL1-α3. During further conditioning, this diminished feedback allows these two PPL1-DANs to encode the net innate plus learnt valence of the conditioned odor cue, which gates long-term memory formation. A computational model constrained by the fly connectome6,7 and our spiking data explains how dopamine signals mediate the circuit interactions between short- and long-term memory traces, yielding predictions that our experiments confirm. Overall, the mushroom body achieves flexible learning via the integration of innate and learnt valences within parallel learning units sharing feedback interconnections. This hybrid physiologic-anatomic mechanism may be a general means by which dopamine regulates memory dynamics in other species and brain structures, including the vertebrate basal ganglia.
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In classical cerebellar learning, Purkinje cells (PkCs) associate climbing fiber (CF) error signals with predictive granule cells (GrCs) that were active just prior (â¼150 ms). The cerebellum also contributes to behaviors characterized by longer timescales. To investigate how GrC-CF-PkC circuits might learn seconds-long predictions, we imaged simultaneous GrC-CF activity over days of forelimb operant conditioning for delayed water reward. As mice learned reward timing, numerous GrCs developed anticipatory activity ramping at different rates until reward delivery, followed by widespread time-locked CF spiking. Relearning longer delays further lengthened GrC activations. We computed CF-dependent GrCâPkC plasticity rules, demonstrating that reward-evoked CF spikes sufficed to grade many GrC synapses by anticipatory timing. We predicted and confirmed that PkCs could thereby continuously ramp across seconds-long intervals from movement to reward. Learning thus leads to new GrC temporal bases linking predictors to remote CF reward signals-a strategy well suited for learning to track the long intervals common in cognitive domains.
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Cerebelo , Aprendizaje , Células de Purkinje , Recompensa , Animales , Cerebelo/fisiología , Cerebelo/citología , Ratones , Células de Purkinje/fisiología , Aprendizaje/fisiología , Condicionamiento Operante/fisiología , Masculino , Ratones Endogámicos C57BL , Fibras Nerviosas/fisiología , Plasticidad Neuronal/fisiología , Neuronas/fisiología , Factores de Tiempo , Potenciales de Acción/fisiologíaRESUMEN
The development of voltage-sensitive fluorescent probes suggests fluorescence lifetime as a promising readout for electrical activity in biological systems. Existing approaches fail to achieve the speed and sensitivity required for voltage imaging in neuroscience applications. We demonstrated that wide-field electro-optic fluorescence lifetime imaging microscopy (EO-FLIM) allows lifetime imaging at kilohertz frame-acquisition rates, spatially resolving action potential propagation and subthreshold neural activity in live adult Drosophila. Lifetime resolutions of <5 picoseconds at 1 kilohertz were achieved for single-cell voltage recordings. Lifetime readout is limited by photon shot noise, and the method provides strong rejection of motion artifacts and technical noise sources. Recordings revealed local transmembrane depolarizations, two types of spikes with distinct fluorescence lifetimes, and phase locking of spikes to an external mechanical stimulus.
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Potenciales de Acción , Neuronas , Imagen Óptica , Colorantes Fluorescentes , Microscopía Fluorescente/métodos , Neuronas/fisiología , Imagen Óptica/métodos , Animales , Drosophila melanogasterRESUMEN
The hypothalamus regulates innate social behaviors, including mating and aggression. These behaviors can be evoked by optogenetic stimulation of specific neuronal subpopulations within MPOA and VMHvl, respectively. Here, we perform dynamical systems modeling of population neuronal activity in these nuclei during social behaviors. In VMHvl, unsupervised analysis identified a dominant dimension of neural activity with a large time constant (>50 s), generating an approximate line attractor in neural state space. Progression of the neural trajectory along this attractor was correlated with an escalation of agonistic behavior, suggesting that it may encode a scalable state of aggressiveness. Consistent with this, individual differences in the magnitude of the integration dimension time constant were strongly correlated with differences in aggressiveness. In contrast, approximate line attractors were not observed in MPOA during mating; instead, neurons with fast dynamics were tuned to specific actions. Thus, different hypothalamic nuclei employ distinct neural population codes to represent similar social behaviors.
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Conducta Sexual Animal , Núcleo Hipotalámico Ventromedial , Animales , Conducta Sexual Animal/fisiología , Núcleo Hipotalámico Ventromedial/fisiología , Hipotálamo/fisiología , Agresión/fisiología , Conducta SocialRESUMEN
Genetically encoded fluorescent voltage indicators are ideally suited to reveal the millisecond-scale interactions among and between targeted cell populations. However, current indicators lack the requisite sensitivity for in vivo multipopulation imaging. We describe next-generation green and red voltage sensors, Ace-mNeon2 and VARNAM2, and their reverse response-polarity variants pAce and pAceR. Our indicators enable 0.4- to 1-kilohertz voltage recordings from >50 spiking neurons per field of view in awake mice and ~30-minute continuous imaging in flies. Using dual-polarity multiplexed imaging, we uncovered brain state-dependent antagonism between neocortical somatostatin-expressing (SST+) and vasoactive intestinal peptide-expressing (VIP+) interneurons and contributions to hippocampal field potentials from cell ensembles with distinct axonal projections. By combining three mutually compatible indicators, we performed simultaneous triple-population imaging. These approaches will empower investigations of the dynamic interplay between neuronal subclasses at single-spike resolution.
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Potenciales de Acción , Hipocampo , Imagen Molecular , Neuronas , Corteza Visual , Animales , Ratones , Potenciales de Acción/fisiología , Hipocampo/citología , Hipocampo/fisiología , Interneuronas/fisiología , Neuronas/clasificación , Neuronas/fisiología , Péptido Intestinal Vasoactivo/metabolismo , Imagen Molecular/métodos , Rodopsina/química , Rodopsina/genética , Proteínas Luminiscentes/química , Proteínas Luminiscentes/genética , Corteza Visual/citología , Corteza Visual/fisiología , Fluorescencia , Mediciones LuminiscentesRESUMEN
Neurons in the CA1 area of the mouse hippocampus encode the position of the animal in an environment. However, given the variability in individual neurons responses, the accuracy of this code is still poorly understood. It was proposed that downstream areas could achieve high spatial accuracy by integrating the activity of thousands of neurons, but theoretical studies point to shared fluctuations in the firing rate as a potential limitation. Using high-throughput calcium imaging in freely moving mice, we demonstrated the limiting factors in the accuracy of the CA1 spatial code. We found that noise correlations in the hippocampus bound the estimation error of spatial coding to ~10 cm (the size of a mouse). Maximal accuracy was obtained using approximately [300-1400] neurons, depending on the animal. These findings reveal intrinsic limits in the brain's representations of space and suggest that single neurons downstream of the hippocampus can extract maximal spatial information from several hundred inputs.
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Hipocampo , Neuronas , Potenciales de Acción/fisiología , Animales , Hipocampo/fisiología , Ratones , Neuronas/fisiologíaRESUMEN
Reliable sensory discrimination must arise from high-fidelity neural representations and communication between brain areas. However, how neocortical sensory processing overcomes the substantial variability of neuronal sensory responses remains undetermined1-6. Here we imaged neuronal activity in eight neocortical areas concurrently and over five days in mice performing a visual discrimination task, yielding longitudinal recordings of more than 21,000 neurons. Analyses revealed a sequence of events across the neocortex starting from a resting state, to early stages of perception, and through the formation of a task response. At rest, the neocortex had one pattern of functional connections, identified through sets of areas that shared activity cofluctuations7,8. Within about 200 ms after the onset of the sensory stimulus, such connections rearranged, with different areas sharing cofluctuations and task-related information. During this short-lived state (approximately 300 ms duration), both inter-area sensory data transmission and the redundancy of sensory encoding peaked, reflecting a transient increase in correlated fluctuations among task-related neurons. By around 0.5 s after stimulus onset, the visual representation reached a more stable form, the structure of which was robust to the prominent, day-to-day variations in the responses of individual cells. About 1 s into stimulus presentation, a global fluctuation mode conveyed the upcoming response of the mouse to every area examined and was orthogonal to modes carrying sensory data. Overall, the neocortex supports sensory performance through brief elevations in sensory coding redundancy near the start of perception, neural population codes that are robust to cellular variability, and widespread inter-area fluctuation modes that transmit sensory data and task responses in non-interfering channels.
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Neocórtex , Percepción Visual , Animales , Discriminación en Psicología/fisiología , Ratones , Neocórtex/fisiología , Neuronas/fisiología , Reproducibilidad de los Resultados , Percepción Visual/fisiologíaRESUMEN
Recent progress in fluorescence imaging allows neuroscientists to observe the dynamics of thousands of individual neurons, identified genetically or by their connectivity, across multiple brain areas and for extended durations in awake behaving mammals. We discuss advances in fluorescent indicators of neural activity, viral and genetic methods to express these indicators, chronic animal preparations for long-term imaging studies, and microscopes to monitor and manipulate the activity of large neural ensembles. Ca2+ imaging studies of neural activity can track brain area interactions and distributed information processing at cellular resolution. Across smaller spatial scales, high-speed voltage imaging reveals the distinctive spiking patterns and coding properties of targeted neuron types. Collectively, these innovations will propel studies of brain function and dovetail with ongoing neuroscience initiatives to identify new neuron types and develop widely applicable, non-human primate models. The optical toolkit's growing sophistication also suggests that "brain observatory" facilities would be useful open resources for future brain-imaging studies.
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Mapeo Encefálico/métodos , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Neocórtex/diagnóstico por imagen , Neocórtex/metabolismo , Neuronas/metabolismo , Imagen Óptica/métodos , Animales , Calcio/metabolismo , Ratones , Modelos Animales , Neurociencias/métodosRESUMEN
Locomotor speed is a basic input used to calculate one's position, but where this signal comes from is unclear. We identified neurons in the supramammillary nucleus (SuM) of the rodent hypothalamus that were highly correlated with future locomotor speed and reliably drove locomotion when activated. Robust locomotion control was specifically identified in Tac1 (substance P)expressing (SuMTac1+) neurons, the activation of which selectively controlled the activity of speed-modulated hippocampal neurons. By contrast, Tac1-deficient (SuMTac1−) cells weakly regulated locomotion but potently controlled the spike timing of hippocampal neurons and were sufficient to entrain local network oscillations. These findings emphasize that the SuM not only regulates basic locomotor activity but also selectively shapes hippocampal neural activity in a manner that may support spatial navigation.
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Hipocampo/fisiología , Hipotálamo Posterior/fisiología , Locomoción , Neuronas/fisiología , Potenciales de Acción , Animales , Hipocampo/citología , Hipotálamo Posterior/citología , Ratones , Ratones Endogámicos C57BL , Vías Nerviosas/fisiología , Ratas , Navegación Espacial , Sustancia P/genética , Ritmo TetaRESUMEN
In motor neuroscience, state changes are hypothesized to time-lock neural assemblies coordinating complex movements, but evidence for this remains slender. We tested whether a discrete change from more autonomous to coherent spiking underlies skilled movement by imaging cerebellar Purkinje neuron complex spikes in mice making targeted forelimb-reaches. As mice learned the task, millimeter-scale spatiotemporally coherent spiking emerged ipsilateral to the reaching forelimb, and consistent neural synchronization became predictive of kinematic stereotypy. Before reach onset, spiking switched from more disordered to internally time-locked concerted spiking and silence. Optogenetic manipulations of cerebellar feedback to the inferior olive bi-directionally modulated neural synchronization and reaching direction. A simple model explained the reorganization of spiking during reaching as reflecting a discrete bifurcation in olivary network dynamics. These findings argue that to prepare learned movements, olivo-cerebellar circuits enter a self-regulated, synchronized state promoting motor coordination. State changes facilitating behavioral transitions may generalize across neural systems.
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Movimiento/fisiología , Red Nerviosa/fisiología , Potenciales de Acción/fisiología , Animales , Calcio/metabolismo , Cerebelo/fisiología , Sincronización Cortical , Miembro Anterior/fisiología , Interneuronas/fisiología , Aprendizaje , Ratones Endogámicos C57BL , Ratones Transgénicos , Modelos Neurológicos , Actividad Motora/fisiología , Núcleo Olivar/fisiología , Optogenética , Células de Purkinje/fisiología , Conducta Estereotipada , Análisis y Desempeño de TareasRESUMEN
Cerebellar granule cells (GrCs) are usually regarded as a uniform cell type that collectively expands the coding space of the cerebellum by integrating diverse combinations of mossy fiber inputs. Accordingly, stable molecularly or physiologically defined GrC subtypes within a single cerebellar region have not been reported. The only known cellular property that distinguishes otherwise homogeneous GrCs is the correspondence between GrC birth timing and the depth of the molecular layer to which their axons project. To determine the role birth timing plays in GrC wiring and function, we developed genetic strategies to access early- and late-born GrCs. We initiated retrograde monosynaptic rabies virus tracing from control (birth timing unrestricted), early-born, and late-born GrCs, revealing the different patterns of mossy fiber input to GrCs in vermis lobule 6 and simplex, as well as to early- and late-born GrCs of vermis lobule 6: sensory and motor nuclei provide more input to early-born GrCs, while basal pontine and cerebellar nuclei provide more input to late-born GrCs. In vivo multidepth two-photon Ca2+ imaging of axons of early- and late-born GrCs revealed representations of diverse task variables and stimuli by both populations, with modest differences in the proportions encoding movement, reward anticipation, and reward consumption. Our results suggest neither organized parallel processing nor completely random organization of mossy fiberâGrC circuitry but instead a moderate influence of birth timing on GrC wiring and encoding. Our imaging data also provide evidence that GrCs can represent generalized responses to aversive stimuli, in addition to recently described reward representations.
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Corteza Cerebelosa/crecimiento & desarrollo , Fibras Nerviosas/metabolismo , Animales , Animales Recién Nacidos , Corteza Cerebelosa/virología , Ratones , Ratones Transgénicos , Fibras Nerviosas/virología , Virus de la Rabia/metabolismoRESUMEN
Organisms must learn new strategies to adapt to changing environments. Activity in different neurons often exhibits synchronization that can dynamically enhance their communication and might create flexible brain states that facilitate changes in behavior. We studied the role of gamma-frequency (~40 Hz) synchrony between prefrontal parvalbumin (PV) interneurons in mice learning multiple new cue-reward associations. Voltage indicators revealed cell-type-specific increases of cross-hemispheric gamma synchrony between PV interneurons when mice received feedback that previously learned associations were no longer valid. Disrupting this synchronization by delivering out-of-phase optogenetic stimulation caused mice to perseverate on outdated associations, an effect not reproduced by in-phase stimulation or out-of-phase stimulation at other frequencies. Gamma synchrony was specifically required when new associations used familiar cues that were previously irrelevant to behavioral outcomes, not when associations involved new cues or for reversing previously learned associations. Thus, gamma synchrony is indispensable for reappraising the behavioral salience of external cues.
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Adaptación Fisiológica/fisiología , Aprendizaje por Asociación/fisiología , Ritmo Gamma/fisiología , Interneuronas/fisiología , Corteza Prefrontal/fisiología , Animales , Señales (Psicología) , Femenino , Lateralidad Funcional , Masculino , Ratones , Parvalbúminas/metabolismo , RecompensaRESUMEN
How the brain processes information accurately despite stochastic neural activity is a longstanding question1. For instance, perception is fundamentally limited by the information that the brain can extract from the noisy dynamics of sensory neurons. Seminal experiments2,3 suggest that correlated noise in sensory cortical neural ensembles is what limits their coding accuracy4-6, although how correlated noise affects neural codes remains debated7-11. Recent theoretical work proposes that how a neural ensemble's sensory tuning properties relate statistically to its correlated noise patterns is a greater determinant of coding accuracy than is absolute noise strength12-14. However, without simultaneous recordings from thousands of cortical neurons with shared sensory inputs, it is unknown whether correlated noise limits coding fidelity. Here we present a 16-beam, two-photon microscope to monitor activity across the mouse primary visual cortex, along with analyses to quantify the information conveyed by large neural ensembles. We found that, in the visual cortex, correlated noise constrained signalling for ensembles with 800-1,300 neurons. Several noise components of the ensemble dynamics grew proportionally to the ensemble size and the encoded visual signals, revealing the predicted information-limiting correlations12-14. Notably, visual signals were perpendicular to the largest noise mode, which therefore did not limit coding fidelity. The information-limiting noise modes were approximately ten times smaller and concordant with mouse visual acuity15. Therefore, cortical design principles appear to enhance coding accuracy by restricting around 90% of noise fluctuations to modes that do not limit signalling fidelity, whereas much weaker correlated noise modes inherently bound sensory discrimination.
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Células Receptoras Sensoriales/fisiología , Agudeza Visual/fisiología , Corteza Visual/citología , Corteza Visual/fisiología , Animales , Femenino , Masculino , Ratones , Estimulación Luminosa , Procesos EstocásticosRESUMEN
Skilled forelimb behaviors are among the most important for studying motor learning in multiple species including humans. This protocol describes learned forelimb tasks for mice using a two-axis robotic manipulandum. Our device provides a highly compact adaptation of actuated planar two-axis arms that is simple and inexpensive to construct. This paradigm has been dominant for decades in primate motor neuroscience. Our device can generate arbitrary virtual movement tracks, arbitrary time-varying forces or arbitrary position- or velocity-dependent force patterns. We describe several example tasks permitted by our device, including linear movements, movement sequences and aiming movements. We provide the mechanical drawings and source code needed to assemble and control the device, and detail the procedure to train mice to use the device. Our software can be simply extended to allow users to program various customized movement assays. The device can be assembled in a few days, and the time to train mice on the tasks that we describe ranges from a few days to several weeks. Furthermore, the device is compatible with various neurophysiological techniques that require head fixation.
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Miembro Anterior , Movimiento , Desempeño Psicomotor/fisiología , Robótica/instrumentación , Robótica/métodos , Animales , Fenómenos Biomecánicos , Cabeza , RatonesRESUMEN
Amyotrophic lateral sclerosis (ALS) is a fatal disease involving motor neuron degeneration. Effective diagnosis of ALS and quantitative monitoring of its progression are crucial to the success of clinical trials. Second harmonic generation (SHG) microendoscopy is an emerging technology for imaging single motor unit contractions. To assess the potential value of microendoscopy for diagnosing and tracking ALS, we monitored motor unit dynamics in a B6.SOD1G93A mouse model of ALS for several weeks. Prior to overt symptoms, muscle twitch rise and relaxation time constants both increased, consistent with a loss of fast-fatigable motor units. These effects became more pronounced with disease progression, consistent with the death of fast fatigue-resistant motor units and superior survival of slow motor units. From these measurements we constructed a physiological metric that reflects the changing distributions of measured motor unit time constants and effectively diagnoses mice before symptomatic onset and tracks disease state. These results indicate that SHG microendoscopy provides a means for developing a quantitative, physiologic characterization of ALS progression.
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Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/fisiopatología , Endoscopía , Contracción Muscular , Esclerosis Amiotrófica Lateral/patología , Animales , Recuento de Células , Modelos Animales de Enfermedad , Femenino , Ratones , Neuronas Motoras/patologíaRESUMEN
Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we show single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution and with repeated sampling over days. In the visual cortex, we use soma-targeted ASAP3 to illustrate cell-type-dependent subthreshold modulation by locomotion. Thus, ASAP3 and ULoVE enable high-speed optical recording of electrical activity in genetically defined neurons at deep locations during awake behavior.
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Encéfalo/fisiología , Proteínas Activadoras de GTPasa/genética , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Optogenética/métodos , Ritmo Teta , Vigilia , Potenciales de Acción , Animales , Encéfalo/metabolismo , Células CHO , Células Cultivadas , Cricetinae , Cricetulus , Femenino , Proteínas Activadoras de GTPasa/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/metabolismo , Ratas , Ratas Sprague-Dawley , CarreraRESUMEN
Two-photon microscopy is a mainstay technique for imaging in scattering media and normally provides frame-acquisition rates of ~10-30 Hz. To track high-speed phenomena, we created a two-photon microscope with 400 illumination beams that collectively sample 95,000-211,000 µm2 areas at rates up to 1 kHz. Using this microscope, we visualized microcirculatory flow, fast venous constrictions and neuronal Ca2+ spiking with millisecond-scale timing resolution in the brains of awake mice.
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Encéfalo/irrigación sanguínea , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Animales , Calcio/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Microcirculación , VigiliaRESUMEN
Throughout mammalian neocortex, layer 5 pyramidal (L5) cells project via the pons to a vast number of cerebellar granule cells (GrCs), forming a fundamental pathway. Yet, it is unknown how neuronal dynamics are transformed through the L5âGrC pathway. Here, by directly comparing premotor L5 and GrC activity during a forelimb movement task using dual-site two-photon Ca2+ imaging, we found that in expert mice, L5 and GrC dynamics were highly similar. L5 cells and GrCs shared a common set of task-encoding activity patterns, possessed similar diversity of responses, and exhibited high correlations comparable to local correlations among L5 cells. Chronic imaging revealed that these dynamics co-emerged in cortex and cerebellum over learning: as behavioral performance improved, initially dissimilar L5 cells and GrCs converged onto a shared, low-dimensional, task-encoding set of neural activity patterns. Thus, a key function of cortico-cerebellar communication is the propagation of shared dynamics that emerge during learning.