Biology subjects

Miri, A.

Publications and source records attributed to Miri, A..

10 recordsLinked to original sources

bioRxiv2026

Multi-area activity in mouse motor cortex associated with one- and two-handed oromanual dexterity

Cortical dynamics during goal-directed dexterous hand movements are mainly understood from paradigms involving use of the contralateral hand. To study how movement-related activity changes when the ipsilateral or both hands are used, we exploited a natural form of rodent manual dexterity - food handling - that rodents can perform uni- or bimanually. We sampled kilohertz 3D kinematics as mice used either or both hands to manipulate food, while recording spiking activity in forelimb primary (fl-M1) and secondary (fl-M2) motor cortices, and in a lateral oral and manual (LOM) motor cortex area implicated in oromanual food handling. Unit- and population-level analyses showed that activity in fl-M1 and fl-M2 depended on both laterality (ipsi- vs contralateral) and "manuality" (uni- vs bimanual), with few differences between the two areas. By comparison, activity in LOM was largely laterality- and manuality-invariant. These results demonstrate how activity in multiple areas of mouse motor cortex varies as the same task is performed unimanually with either hand or bimanually with both. Our findings support a model in which fl-M1 and fl-M2 maintain separable information about both forelimbs for bimanual coordination, while LOM encodes ingestion-related forelimb parameters necessary for oromanual coordination.

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bioRxiv2025

Constraining inference of across-region interactions using neural activity perturbations

Functional interactions between brain regions are often inferred from multi-region models fit to neural activity recorded in behaving animals. Here, we show that inference of acrossregion interactions is hindered by the wide breadth of model fits consistent with naturally occurring neural activity. In contrast, models fit to activity that includes region-wide activity perturbations provide well-constrained estimates of across-region interactions; simulations suggest these estimates can be accurate.

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bioRxiv2025

A brain-wide, trial- and time-dependent deterministic drive for self-initiated action decisions

Deciding when to act in the absence of external cues is essential for exploration, learning, and survival. Yet the neural mechanisms underlying such decisions remain controversial, with current views favoring either deterministic or stochastic underpinnings. We simultaneously recorded from large neuronal populations in cortical, thalamic, pallidal, and cerebellar regions as mice self-initiated voluntary actions. Action onset timing was predictable from firing patterns up to several seconds in advance with predictions correlated across regions, demonstrating a prominent deterministic drive that spans regions. Computational modeling indicated that this drive has an initial value and rate that vary trial-by-trial, and the rate increases within trials. Although the deterministic drive is sufficient to trigger action, noise within trials also contributes to setting action timing. Therefore, discrete (across-trial) and continuous (within-trial) sources of variability synergize to time self-initiated actions. This synergy is observed brain-wide, suggesting a distributed decision-making process rather than a hierarchical, modular one.

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bioRxiv2025

Interactions between motor cortical forelimb regions and their influence on muscles reorganize across behaviors

It remains unclear how classical models of motor cortical hierarchy align with emerging evidence of behavioral organization in motor cortex. To address this, we combined optogenetic inactivation, Neuropixels recording, and electromyography to quantify the pattern and influence of activity in the mouse analogs of forelimb premotor and primary motor cortex (RFA and CFA) during reaching and climbing. Results revealed that RFAs dominant influence on forelimb muscles and on CFA during reaching is replaced by a dominant influence of CFA on muscles and on RFA during climbing, even when forelimb muscle activity during climbing resembles that during reaching. Short-latency influence between regions on excitatory and inhibitory populations in different cortical laminae also showed behavioral specificity. Simultaneous recordings in both areas during climbing revealed a loss of activity timing differences seen during reaching previously interpreted as reflective of hierarchy. These findings demonstrate that hierarchical interactions between forelimb motor cortical regions are behavior-specific.

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bioRxiv2024

Neural dynamics hierarchy in motor cortex and striatum across naturalistic behaviors

Mammals perform a wide range of movements actuated by diverse patterns of muscle activity. Primary motor cortex (M1) and striatum are implicated in controlling these movements, but how their activity dynamics are organized to accommodate such diversity is poorly understood. We developed a paradigm that enabled us to investigate neural dynamics across diverse motor behaviors in mice. In contrast to existing views, we found neither behavior-specific nor behavior-invariant organization in single-neuron activity, population-level covariation, and muscle activity correlation. Instead, the similarity of activity dynamics between behaviors varied differentially across behavior pairs, forming a hierarchical organization. The same hierarchical organization was shared between M1 and striatum, despite stronger muscle activity correlation in M1 and greater behavior specificity in striatum. Network modeling indicated that striatal activity is sufficient to drive hierarchical dynamics in muscle pattern-generating circuits. These hierarchical dynamics may reflect a tradeoff between behavioral specialization and generalization in motor system function.

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bioRxiv2024

Distinct anatomical and functional corticospinal inputs innervate different spinal neuron types

The corticospinal tract exerts its influence on movement through spinal neurons, which can be divided into types that exhibit distinct functions. However, it remains unknown whether these functional distinctions are reflected in the corticospinal inputs that different types of spinal neurons receive. Using rabies monosynaptic tracing from individual neuron types in the cervical cord and 3D histological reconstruction in mice, we discovered that different types receive inputs distinctly distributed across cortex, and aligned with cell type function. This included a distinct, sparse distribution of direct inputs from cortex onto motor neurons. Coupling rabies tracing with activity measurement during motor behavior revealed different interneuron types receive different input activity patterns, primarily due to the topographical distribution of the corticospinal neurons contacting them. Our results establish that different spinal neuron types get distinct anatomical and functional inputs from the cortex, and reveal functionally relevant homology to primate corticospinal organization.

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bioRxiv2023

Hierarchy in influence but not firing patterns among forelimb motor cortices

Though hierarchy is commonly invoked in descriptions of motor cortical function, its presence and manifestation in firing patterns remain poorly resolved. Here we use optogenetic inactivation to demonstrate that short-latency influence between forelimb premotor and primary motor cortices is asymmetric during reaching in mice, demonstrating a partial hierarchy between the endogenous activity in each region. Multi-region recordings revealed that some activity is captured by similar but delayed patterns where either regions activity leads, with premotor activity leading more. Yet firing in each region is dominated by patterns shared between regions and is equally predictive of firing in the other region at the single-neuron level. In dual-region network models fit to data, regions differed in their dependence on across-region input, rather than the amount of such input they received. Our results indicate that motor cortical hierarchy, while present, may not be exposed when inferring interactions between populations from firing patterns alone.

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bioRxiv2023

A distinct neural activity subspace for direct motor cortical influence on muscles

It remains poorly resolved when and how motor cortical output directly influences limb muscle activity through descending projections, which impedes mechanistic understanding of motor control. Here we addressed this in mice performing an ethologically inspired climbing behavior. We quantified the direct influence of forelimb primary motor cortex (caudal forelimb area, CFA) on muscles across the muscle activity states expressed during climbing. We found that CFA instructs muscle activity pattern by selectively activating certain muscles, while less frequently activating or suppressing their antagonists. From Neuropixels recordings, we identified linear combinations (components) of motor cortical activity that covary with these effects. These components differ partially from those that covary with muscle activity and differ almost completely from those that covary with kinematics. Collectively, our results reveal an instructive direct motor cortical influence on limb muscles that is selective within a motor behavior and reliant on a distinct neural activity subspace.

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bioRxiv2022

Motor cortical influence relies on task-specific activity covariation

During limb movement, spinal circuits facilitate the alternating activation of antagonistic flexor and extensor muscles. Yet antagonist cocontraction is often required to stabilize joints, like when loads are handled. Previous results suggest that these different muscle activation patterns are mediated by separate flexion- and extension-related motor cortical output populations, while others suggest recruitment of task-specific populations. To distinguish between hypotheses, we developed a paradigm in which mice toggle between forelimb tasks requiring antagonist alternation or cocontraction and measured activity in motor cortical layer 5b. Our results conformed to neither hypothesis: consistent flexion- and extension-related activity was not observed across tasks, and no task-specific populations were observed. Instead, activity covariation among motor cortical neurons dramatically changed between tasks, thereby altering the relation between neural and muscle activity. This was also observed specifically for corticospinal neurons. Collectively, our findings indicate that motor cortex drives different muscle activation patterns via task-specific activity covariation. HIGHLIGHTSO_LIMice perform two forelimb tasks involving distinct antagonist muscle activity in a novel paradigm C_LIO_LIL5b motor cortical neurons are not organized by task-specific activity C_LIO_LIL5b motor cortical neurons do not encode muscle activity consistently across tasks C_LIO_LITask-specific muscle activity is driven by a change in motor cortical activity covariation C_LI eTOC BLURBWarriner et al. simultaneously measured muscle and motor cortical activity in mouse during antagonist forelimb muscle alternation and cocontraction, revealing that these distinct muscle activation patterns are not driven through consistent flexion and extension programs nor through the activity of discrete, task-specific neuronal subsets. Instead, distinct patterns involve task-specific changes in firing pattern covariation among layer 5b neurons, and corticospinal neurons in particular, which change their relationship to muscle activity across tasks.

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bioRxiv2021

Oculomotor plant and neural dynamics suggest gaze control requires integration on distributed timescales

A fundamental principle of biological motor control is that the neural commands driving movement must conform to the response properties of the motor plants they control. In the oculomotor system, characterizations of oculomotor plant dynamics traditionally supported models in which the plant responds to neural drive to extraocular muscles on exclusively short, subsecond timescales. These models predict that the stabilization of gaze during fixations between saccades requires neural drive that approximates eye position on longer timescales and is generated through the temporal integration of brief eye velocity-encoding signals that cause saccades. However, recent measurements of oculomotor plant behaviour have revealed responses on longer timescales. Furthermore, measurements of firing patterns in the oculomotor integrator have revealed a more complex encoding of eye movement dynamics. Yet, the link between these observations has remained unclear. Here we use measurements from the larval zebrafish to link dynamics in the oculomotor plant to dynamics in the neural integrator. The oculomotor plant in both anaesthetized and awake larval zebrafish was characterized by a broad distribution of response timescales, including those much longer than one second. Analysis of the firing patterns of oculomotor integrator neurons, which exhibited a broadly distributed range of decay time constants, demonstrates the sufficiency of this activity for stabilizing gaze given an oculomotor plant with distributed response timescales. This work suggests that leaky integration on multiple, distributed timescales by the oculomotor integrator reflects an inverse model for generating oculomotor commands, and that multi-timescale dynamics may be a general feature of motor circuitry. KEY POINTSO_LIRecent observations of oculomotor plant response properties and neural activity across the oculomotor system have called into question classical formulations of both the oculomotor plant and the oculomotor integrator. C_LIO_LIHere we use measurements from new and published experiments in the larval zebrafish together with modelling to reconcile recent oculomotor plant observations with oculomotor integrator function. C_LIO_LIWe developed computational techniques to characterize oculomotor plant responses over several seconds in awake animals, demonstrating that long timescale responses seen in anesthetized animals extend to the awake state. C_LIO_LIAnalysis of firing patterns of oculomotor integrator neurons demonstrates the sufficiency of this activity for stabilizing gaze given an oculomotor plant with multiple, distributed response timescales. C_LIO_LIOur results support a formulation of gaze stabilization by the oculomotor system in which commands for stabilizing gaze are generated through integration on multiple, distributed timescales. C_LI

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