Biology subjects

Dacre, J.

Publications and source records attributed to Dacre, J..

4 recordsLinked to original sources

bioRxiv2026

Thalamic input drives co-timed excitation and inhibition to suppress cortical neuronal variability during movement initiation

Cortical activity is inherently dynamic, with ongoing fluctuations introducing variability into sensory-to-motor transformations. During movement initiation, neural variability in the motor cortex is sharply reduced, or "quenched," a general phenomenon thought to ensure reliable population responses across cortical areas. However, the synaptic and circuit-level basis for this reduction in neural variability remains unclear. Here, we show that excitatory and inhibitory neurons in layer 5B of mouse motor cortex are co-activated during movement initiation in a cued forelimb push task. Co-timed excitation and inhibition drive pyramidal neuron membrane potential (Vm) trajectories towards the compound synaptic reversal potential, stabilizing the Vm and reducing trial-by-trial variability. Gain- and loss-of-function experiments demonstrate that thalamocortical input is critical for the coordinated recruitment of both excitation and inhibition and variability quenching at the cellular level, while also driving a cortical network state permissive for the expression of reproducible output dynamics. Our findings uncover a simple yet fundamental feedforward mechanism where thalamic input drives neural variability quenching to ensure reliable, structured population dynamics during movement initiation.

neuroscience↗

bioRxiv2023

A cranial implant for stabilizing whole-cell patch-clamp recordings in behaving rodents

BackgroundIn vivo patch-clamp recording techniques provide access to the sub- and suprathreshold membrane potential dynamics of individual neurons during behavior. However, maintaining recording stability throughout behavior is a significant challenge, and while methods for head restraint are commonly used to enhance stability, behaviorally related brain movement relative to the skull can severely impact the success rate and duration of whole-cell patch-clamp recordings. New methodWe developed a low-cost, biocompatible, and 3D-printable cranial implant capable of locally stabilizing brain movement, while permitting equivalent access to the brain when compared to a conventional craniotomy. ResultsExperiments in head-restrained behaving mice demonstrate that the cranial implant can reliably reduce the amplitude and speed of brain displacements, significantly improving the success rate of recordings across repeated bouts of motor behavior. Comparison with existing methodsOur solution offers an improvement on currently available strategies for brain stabilization. Due to its small size, the implant can be retrofitted to most in vivo electrophysiology recording setups, providing a low cost, easily implementable solution for increasing intracellular recording stability in vivo. ConclusionsBy facilitating stable whole-cell patch-clamp recordings in vivo, biocompatible 3D printed implants should accelerate the investigation of single neuron computations underlying behavior.

neuroscience↗

bioRxiv2022

Multiscale model of primary motor cortex circuits reproduces in vivo cell type-specific dynamics associated with behavior

Understanding cortical function requires studying multiple scales: molecular, cellular, circuit and behavior. We developed a biophysically detailed multiscale model of mouse primary motor cortex (M1) with over 10,000 neurons and 30 million synapses. Neuron types, densities, spatial distributions, morphologies, biophysics, connectivity and dendritic synapse locations were tightly constrained by experimental data. The model includes long-range inputs from 7 thalamic and cortical regions, as well as noradrenergic inputs from locus coeruleus. Connectivity depended on cell class and cortical depth at sublaminar resolution. The model accurately predicted in vivo layer- and cell type-specific responses (firing rates and LFP) associated with behavioral states (quiet wakefulness and movement) and experimental manipulations (noradrenaline receptor blocking and thalamus inactivation). It also enabled evaluation of multiple mechanistic hypotheses underlying the observed activity. This quantitative theoretical framework can be used to integrate and interpret M1 experimental data and sheds light on the cell type-specific multiscale dynamics associated with a range of experimental conditions and behaviors.

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↗