Temporally precise movement-based predictions in the mouse auditory cortex

Many of the sensations experienced by an organism are caused by their own actions, and accurately anticipating both the sensory features and timing of self-generated stimuli is crucial to a variety of behaviors. In the auditory cortex, neural responses to self-generated sounds exhibit frequency-specific suppression, suggesting that movement-based predictions may be implemented early in sensory processing. Yet it remains unknown whether this modulation results from a behaviorally specific and temporally precise prediction, nor is it known whether corresponding expectation signals are present locally in the auditory cortex. To address these questions, we trained mice to expect the precisely timed acoustic outcome of a forelimb movement using a closed-loop sound-generating lever. Dense neuronal recordings in the auditory cortex revealed suppression of responses to self-generated sounds that was specific to the expected acoustic features, specific to a precise time within the movement, and specific to the movement that was coupled to sound during training. Predictive suppression was concentrated in L2/3 and L5, where deviations from expectation also recruited a population of prediction-error neurons that was otherwise unresponsive. Recording in the absence of sound revealed abundant movement signals in deep layers that were biased toward neurons tuned to the expected sound, as well as temporal expectation signals that were present throughout the cortex and peaked at the time of expected auditory feedback. Together, these findings reveal that predictive processing in the mouse auditory cortex is consistent with a learned internal model linking a specific action to its temporally precise acoustic outcome, while identifying distinct populations of neurons that anticipate expected stimuli and differentially process expected versus unexpected outcomes.

Transient dopamine neuron activity precedes and encodes the vigor of contralateral movements

SummaryDopamine neurons (DANs) in the substantia nigra pars compacta (SNc) have been related to movement vigor, and loss of these neurons leads to bradykinesia in Parkinson’s disease. However, it remains unclear whether DANs encode a general motivation signal or modulate movement kinematics. We imaged activity of SNc DANs in mice trained in a novel operant task which relies on individual forelimb movement sequences. We uncovered that a similar proportion of SNc DANs increased their activity before ipsi- vs. contralateral forelimb movements. However, the magnitude of this activity was higher for contralateral actions, and was related to contralateral but not ipsilateral action vigor. In contrast, the activity of reward-related DANs, largely distinct from those modulated by movement, was not lateralized. Finally, unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor. These results indicate that movement-initiation DANs encode more than a general motivation signal, and invigorate kinematic aspects of contralateral movements.HighlightsDeveloped a freely-moving task where mice learn rapid individual forelimb sequences.Movement-related DANs encode contralateral but not ipsilateral action vigor.The activity of reward-related DANs is not lateralized.Unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor.eTOC summary: Mendonça et al. show that transient activity in movement-related dopamine neurons in substantia nigra pars compacta encodes contralateral, but not ipsilateral action vigor. Consistently, unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor.

Distributed Motor Control of Limb Movements in Rat Motor and Somatosensory Cortex: The Sensorimotor Amalgam Revisited

Which areas of the neocortex are involved in the control of movement, and how is motor cortex organized across species? Recent studies using long-train intracortical microstimulation demonstrate that in addition to M1, movements can be elicited from somatosensory regions in multiple species. In the rat, M1 hindlimb and forelimb movement representations have long been thought to overlap with somatosensory representations of the hindlimb and forelimb in S1, forming a partial sensorimotor amalgam. Here we use long-train intracortical microstimulation to characterize the movements elicited across frontal and parietal cortex. We found that movements of the hindlimb, forelimb, and face can be elicited from both M1 and histologically defined S1 and that representations of limb movement types are different in these two areas. Stimulation of S1 generates retraction of the contralateral forelimb, while stimulation of M1 evokes forelimb elevation movements that are often bilateral, including a rostral region of digit grasping. Hindlimb movement representations include distinct regions of hip flexion and hindlimb retraction evoked from S1 and hip extension evoked from M1. Our data indicate that both S1 and M1 are involved in the generation of movement types exhibited during natural behavior. We draw on these results to reconsider how sensorimotor cortex evolved.

Functional Suppression of Premotor Activity in a Transient Model of Motor Cortex Injury

ABSTRACTCortical injuries (e.g. – strokes or traumatic brain injuries) can create a host of secondary events that further impair the brain’s sensory, motor, or cognitive capabilities. Here, we attempted to isolate the acute effects of the primary injury – the loss of cortical activity – on rodent motor cortex (caudal forelimb area, CFA) without the secondary effects that arise from damage to cortical tissue. We then observed the effects of this loss of activity on the rodent premotor cortex (rostral forelimb area, RFA). In anesthetized rats, CFA was temporarily inactivated with the GABA-A agonist muscimol, disrupting motor network function while leaving neural connectivity intact. Using intracortical microstimulation (ICMS) techniques, we found that CFA inactivation completely abolished ICMS-evoked forelimb movement from RFA yet spared some CFA evoked-movement. Neural recordings confirmed that neural suppression by muscimol was isolated to CFA and did not spread into RFA. We next observed how CFA inactivation suppressed RFA influence on forelimb muscles by obtaining intramuscular electromyographical (EMG) recordings from forelimb muscles during ICMS. EMG recordings showed that despite the presence of evoked movement in CFA, but not RFA, muscle activation in both areas were similarly reduced. These results suggest that the primary reason for the loss of ICMS-evoked movement in RFA is not reduced forelimb muscle activity, but rather a loss of the specific activity between RFA and CFA. Therefore, within the intact motor network of the rat, RFA’s influence on forelimb movement is mediated by CFA, similar to the premotor and motor organization observed in non-human primates.

Forelimb Movement Disorder in Rat Experimental Model

Study of motor activity is an important part of the experimental models of neural disorders of rats. It is used to study effects of the CNS impairment, however studies on the peripheral nervous system lesions are much less frequent. The aim of the study was to extend the spectrum of experimental models of anterior limb movement disorders in rats by blockade of the right anterior limb brachial plexus with the local anesthetic Marcaine (Ma), or with aqua for injection administered into the same location (Aq) (with control intact group C). Two other groups with anterior limb movement disorders underwent induction of cellular brain edema by water intoxication (MaWI and AqWI). Results showed a lower spontaneous motor activity of animals in all experimental groups versus controls, and lower spontaneous motor activity of animals in the MaWI group compared to other experimental groups in all categories. There was no difference in spontaneous activity between the groups Ma, Aq and AqWI. Our study indicates that alterations of spontaneous motor activity may result from the impaired forelimb motor activity induced by the anesthetic effect of Marcaine, by the volumetric effect of water, as a result of induced brain edema, or due to combination of these individual effects.

Prediction of Forelimb EMGs and Movement Phases from Corticospinal Signals in the Rat During the Reach-to-Pull Task

Brain-computer interfaces access the volitional command signals from various brain areas in order to substitute for the motor functions lost due to spinal cord injury or disease. As the final common pathway of the central nervous system (CNS) outputs, the descending tracts of the spinal cord offer an alternative site to extract movement-related command signals. Using flexible 2D microelectrode arrays, we have recorded the corticospinal tract (CST) signals in rats during a reach-to-pull task. The CST activity was then classified by the forelimb movement phases into two or three classes in a training dataset and cross validated in a test set. The average classification accuracies were [Formula: see text] (min: [Formula: see text] to max: [Formula: see text]) and [Formula: see text] (min: 43% to max: 71%) for two-class and three-class cases, respectively. The forelimb flexor and extensor EMG envelopes were also predicted from the CST signals using linear regression. The average correlation coefficient between the actual and predicted EMG signals was [Formula: see text] [Formula: see text], whereas the highest correlation was 0.81 for the biceps EMG. Although the forelimb motor function cannot be explained completely by the CST activity alone, the success rates obtained in reconstructing the EMG signals support the feasibility of a spinal-cord-computer interface as a concept.

Thalamic Inputs to Posterior Parietal Cortical Areas Involved in Skilled Forelimb Movement and Tool Use in the Capuchin Monkey

The posterior parietal cortex (PPC) is a central hub for the primate forebrain networks that control skilled manual behavior, including tool use. Here, we quantified and compared the sources of thalamic input to electrophysiologically-identified hand/forearm-related regions of several PPC areas, namely areas 5v, AIP, PFG, and PF, of the capuchin monkey (Sapajus sp). We found that these areas receive most of their thalamic connections from the Anterior Pulvinar (PuA), Lateral Posterior (LP) and Medial Pulvinar (PuM) nuclei. Each PPC area receives a specific combination of projections from these nuclei, and fewer additional projections from other nuclei. Moreover, retrograde labeling of the cells innervating different PPC areas revealed substantial intermingling of these cells within the thalamus. Differences in thalamic input may contribute to the different functional properties displayed by the PPC areas. Furthermore, the observed innervation of functionally-related PPC domains from partly intermingled thalamic cell populations accords with the notion that higher-order thalamic inputs may dynamically regulate functional connectivity between cortical areas.