Biology subjects

Hantman, A. W.

Publications and source records attributed to Hantman, A. W..

11 recordsLinked to original sources

bioRxiv2026

Synaptic dynamics as a tunable substrate shaping neuronal activity sequences

A central tenet of cerebellar computation posits that granule cells generate sparse spatiotemporal activity patterns that support precisely timed motor and cognitive outputs. Using high-speed in vivo calcium and glutamate imaging combined with slice electrophysiology, we show that heterogeneous synaptic dynamics transform mossy fiber inputs into temporally sparse, sequential patterns of GC activity. Region-specific differences in MF glutamate release shape GC response duration and sparsity, tuning the temporal statistics of population sequences to match sensorimotor associative learning demands. These findings provide direct evidence for temporally sparse GC sequences and establish synaptic dynamics as a ubiquitous, tunable mechanism structuring neural activity in time.

neuroscience↗

bioRxiv2025

Selective coupling and decoupling coordinate distributed brain networks for precise action

The precise and rapid nature of skilled actions has motivated a long-standing theory that preparatory neural states must emerge to enable upcoming actions. This has been best characterized in motor cortex, where neural activity evolves toward an initial state that governs subsequent cortical dynamics. Yet complex actions require coordination across multiple areas beyond motor cortex, and how this distributed network prepares remains unknown. We recorded over 40,000 neurons across the brain as mice produced skilled reach-to-grasp actions, revealing selective coupling of action-informative neurons and decoupling of non-informative neurons over a longer timescale and across a broader network than typically associated with motor preparation. These dynamics predicted upcoming action quality and neural activity on individual trials, and performance was impaired when trials were initiated before coupling and decoupling emerged. Two local field potential rhythms organized these dynamics, providing a target for optogenetic intervention that bidirectionally altered action quality. Our work reveals a distributed preparatory process in which selective coupling and decoupling establish a network state that enables skilled action.

neuroscience↗

bioRxiv2025

Evolutionary expansion of the corticospinal system is linked to dexterity in Peromyscus mice

While the central nervous system is perpetually reshaped by evolution, the principles governing how such changes promote ecologically relevant behaviors without breaking established functions are poorly understood. The expansion of neuron number is a potential mechanism by which the nervous system evolves to support changes in behavior without disrupting existing circuit function. Corticospinal neurons (CSNs) are a classic example: an expansion in the corticospinal system in the primate lineage has been hypothesized to underlie their exceptional dexterity. However, the role of CSN number in behavior has been difficult to assess due to the lack of a tractable model system. We compared two closely related subspecies of deer mice (Peromyscus maniculatus): forest mice, which evolved the ability to adeptly climb, presumably to support a semi-arboreal lifestyle, and prairie mice, which are less proficient climbers. We find that forest mice have about two-fold larger corticospinal tracts (CSTs) driven by an increase in CSN number in secondary motor and sensory cortical areas (M2 and S2). Furthermore, forest mice display greater manual dexterity than their prairie counterparts in a reach-to-grasp task, consistent with the idea that an increase in CSN number supports more dexterous behavior. High-throughput neural recordings during this task revealed a difference in the timing of neural activity between forest and prairie mice, specifically in M2: in forest mice, the peak of activity was shifted towards the grasping phase of the behavior. Forest mice also outperform their prairie counterparts on an ecologically relevant climbing task, where they spend more time upright crossing a thin rod, move faster, and right themselves more quickly when they fall, suggesting a general difference in motor dexterity not restricted to hand use. Finally, we use F2 hybrid animals to show that CST size is correlated with climbing dexterity, providing support for the long-standing hypothesis that corticospinal system expansion supports the evolution of dexterity. Together, our work establishes the forest-prairie deer mouse system as a model to investigate the role of neuron number expansion, and CSNs in particular, in dexterous movement.

neuroscience↗

bioRxiv2025

SORDINO for Silent, Sensitive, Specific, and Artifact-Resisting fMRI in awake behaving mice

Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has revolutionized our understanding of the brain activity landscape, bridging circuit neuroscience in animal models with noninvasive brain mapping in humans. This immensely utilized technique, however, faces challenges such as acoustic noise, electromagnetic interference, motion artifacts, magnetic-field inhomogeneity, and limitations in sensitivity and specificity. Here, we introduce Steady-state On-the-Ramp Detection of INduction-decay with Oversampling (SORDINO), a transformative fMRI technique that addresses these challenges by maintaining a constant total gradient amplitude while acquiring data during continuously changing gradient direction. When benchmarked against conventional fMRI on a 9.4T system, SORDINO is silent, sensitive, specific, and resistant to motion and susceptibility artifacts. SORDINO offers superior compatibility with multimodal experiments and carries novel contrast mechanisms distinct from BOLD. It also enables brain-wide activity and connectivity mapping in awake, behaving mice, overcoming stress- and motion-related confounds that are among the most challenging barriers in current animal fMRI studies.

neuroscience↗

bioRxiv2022

Specific connectivity optimizes learning in thalamocortical loops

1Cortico-thalamo-cortical loops have a central role in cognition and motor control, but precisely how thalamus contributes to these processes is unclear. Recent studies showing evidence of plasticity in thalamocortical synapses indicate a role for thalamus in shaping cortical dynamics - and thus behavior - through learning. Since corticothalamic projections compress cortical activity into a lower-dimensional thalamic activity space, we hypothesized that the computational role of thalamus would depend critically on the structure of corticothalamic connectivity. To test this, we identified the optimal corticothalamic structure that promotes biologically plausible learning in thalamocortical synapses. We found that corticothalamic structures specialized to carry an efference copy of the cortical output benefit motor control, while corticothalamic connections that communicate the directions of highest variance in cortical activity are optimal for working memory tasks. We analyzed neural recordings from mice performing grasping and delayed discrimination, and found corticothalamic interactions consistent with these predictions. These results suggest that thalamus orchestrates cortical dynamics in a functionally precise manner through structured connectivity.

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bioRxiv2020

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings

To study the dynamics of neural processing across timescales, we require the ability to follow the spiking of thousands of individually separable neurons over weeks and months, during unrestrained behavior. To address this need, we introduce the Neuropixels 2.0 probe together with novel analysis algorithms. The new probe has over 5,000 sites and is miniaturized such that two probes plus a headstage, recording 768 sites at once, weigh just over 1 g, suitable for implanting chronically in small mammals. Recordings with high quality signals persisting for at least two months were reliably obtained in two species and six different labs. Improved site density and arrangement combined with new data processing methods enable automatic post-hoc stabilization of data despite brain movements during behavior and across days, allowing recording from the same neurons in the mouse visual cortex for over 2 months. Additionally, an optional configuration allows for recording from multiple sites per available channel, with a penalty to signal-to-noise ratio. These probes and algorithms enable stable recordings from >10,000 sites during free behavior in small animals such as mice.

neuroscience↗

bioRxiv2020

Cell-type specific outcome representation in primary motor cortex

Adaptive movements are critical to animal survival. To guide future actions, the brain monitors different outcomes, including achievement of movement and appetitive goals. The nature of outcome signals and their neuronal and network realization in motor cortex (M1), which commands the performance of skilled movements, is largely unknown. Using a dexterity task, calcium imaging, optogenetic perturbations, and behavioral manipulations, we studied outcome signals in murine M1. We find two populations of layer 2-3 neurons, "success"- and "failure" related neurons that develop with training and report end-result of trials. In these neurons, prolonged responses were recorded after success or failure trials, independent of reward and kinematics. In contrast, the initial state of layer-5 pyramidal tract neurons contains a memory trace of the previous trials outcome. Inter-trial cortical activity was needed to learn new task requirements. These M1 reflective layer-specific performance outcome signals, can support reinforcement motor learning of skilled behavior.

neuroscience↗

bioRxiv2019

Cerebellar-recipient motor thalamus drives behavioral context-specific movement initiation

To initiate goal-directed behavior, animals must transform sensory cues into motor commands that generate appropriately timed actions. Sensorimotor transformations along the cerebellar-thalamocortical pathway are thought to shape motor cortical output and movement timing, but whether this pathway initiates goal-directed movement remains poorly understood. Here, we recorded and perturbed activity in cerebellar-recipient regions of motor thalamus (dentate / interpositus nucleus-recipient regions, MThDN/IPN) and primary motor cortex (M1) in mice trained to execute a cued forelimb lever push task for reward. MThDN/IPN population responses were dominated by a time-locked increase in activity immediately prior to movement that was temporally uncoupled from cue presentation, providing a fixed latency feedforward motor timing signal to M1FL. Blocking MThDN/IPN output suppressed cued movement initiation. Stimulating the MThDN/IPN thalamocortical pathway in the absence of the cue recapitulated cue-evoked M1 membrane potential dynamics and forelimb behavior in the learned behavioral context, but generated semi-random movements in an altered behavioral context. Thus, cerebellar-recipient motor thalamocortical input to M1 is indispensable for the generation of motor commands that initiate goal-directed movement, refining our understanding of how the cerebellar-thalamocortical pathway contributes to movement timing.

neuroscience↗

bioRxiv2019

Flexible routing of motor control signals through neocortical projection neuron classes

The interaction of descending neocortical outputs and subcortical premotor circuits is critical for shaping the skilled movements. Two broad classes of motor cortical output projection neurons provide input to many subcortical motor areas: pyramidal tract neurons (PT), which project throughout the neuraxis; and intratelencephalic neurons (IT), which project within cortex and subcortical striatum. It is unclear whether these classes are functionally in series or whether separable components of descending motor control signals are distributed across these distinct classes of projection neurons. Here we combine large-scale neural recordings across all layers of motor cortex with cell-type specific perturbations to study cortically-dependent mouse motor behaviors: kinematically-variable manipulation of a joystick and a kinematically-precise reach-to-grasp. We find that striatum-projecting IT neuron activity preferentially represents amplitude whereas pons-projecting PT neurons preferentially represent the variable direction of forelimb movements. Thus, separable components of descending motor cortical commands are distributed across motor cortical projection cell classes. One-sentence summarySeparable components of cortical motor commands are distributed across distinct glutamatergic projection neuron cell-types.

neuroscience↗

bioRxiv2019

Reconstruction of 1,000 projection neurons reveals new cell types and organization of long-range connectivity in the mouse brain

Neuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons comprise more than 75 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.

neuroscience↗

bioRxiv2017

Stability, affinity and chromatic variants of the glutamate sensor iGluSnFR

Single-wavelength fluorescent reporters allow visualization of specific neurotransmitters with high spatial and temporal resolution. We report variants of the glutamate sensor iGluSnFR that are functionally brighter; can detect sub-micromolar to millimolar concentrations of glutamate; and have blue, green or yellow emission profiles. These variants allow in vivo imaging where original-iGluSnFR was too dim, reveal glutamate transients at individual spine heads, and permit kilohertz imaging with inexpensive, powerful fiber lasers.

neuroscience↗