Biology subjects

Becker, M. I.

Publications and source records attributed to Becker, M. I..

5 recordsLinked to original sources

bioRxiv2026

Topographic structure and function of locus coeruleus norepinephrine neurons

Norepinephrine (NE) is released throughout most of the central nervous system by neurons in the locus coeruleus (LC). We found a relationship between the morphologies, gene expression, and activity of LC-NE neurons in mice. Axonal projections of individual neurons were extensive but largely confined to subsets of brain regions. Axonal projections and graded gene expression correlated with locations of cell bodies in LC. In a behavioral task requiring ongoing learning from actions, neurons in dorsal LC projecting to the cerebral cortex were excited when mice made a different choice from the previous one and by reward prediction errors, a signal driving learning. Background activity of neurons in ventral LC was higher when mice ignored stimuli indicating potential reward availability. These observations reveal a topographically organized structure and function of a neurotransmitter system and show that it contains learning signals for flexible behavior.

neuroscience↗

bioRxiv2025

Corrective sub-movements link feedback to feedforward control in the cerebellum

The ability to execute accurate movements is thought to rely on both anticipatory feedforward commands and rapid feedback corrections, yet how these control systems are integrated within cerebellar circuits remains unclear. Here, we show that corrective sub-movements (CSMs) - structured, feedback-driven adjustments occurring spontaneously during naturalistic mouse reaching - are not only encoded in anterior interposed (IntA) output neurons, but also act as instructive signals for feedforward learning. Closed-loop perturbations that trigger CSMs lead to learned shifts in the timing of future corrections, even in the absence of further perturbation. Strikingly, this learning depends on the timing of corrective responses, rather than the timing of the error itself, and is accompanied by physiological adaptation in cerebellar output neuronal firing rates. These findings reveal a cerebellar mechanism by which feedback responses train future anticipatory control signals, bridging the gap between reactive and anticipatory motor control in the cerebellum. Key Findings/ HighlightsO_LIMice generate rapid, precise corrective sub-movements (CSMs) during reach that counter both spontaneous variability and induced errors C_LIO_LICerebellar output neurons encode both predictive and corrective movements, mechanistically linking feedforward and feedback control C_LIO_LIClosed-loop optogenetic disruption of cerebellar output induced reach errors that were entirely compensated by CSMs C_LIO_LILearning was driven by the timing of corrective responses, not the timing of the initial error, suggesting an instructive role for CSMs C_LIO_LIBoth reach kinematics and cerebellar nuclear activity adapted over trials of repeated perturbation C_LIO_LIOptogenetic activation of cerebellar output drove errors and subsequent learning, but also blocked expression of that learning acutely, pinpointing cerebellar output as a key site of motor learning expression C_LIO_LIFindings suggest a neural mechanism by which feedback corrections influence learning of feedforward control policies in cerebellar circuits C_LI

neuroscience↗

bioRxiv2021

Cerebellar associative learning underlies skilled reach adaptation

Cerebellar output has been shown to enhance movement precision by scaling the decelerative phase of reaching movements in mice. We hypothesized that during reach, initial kinematics cue late-phase adjustments through cerebellar associative learning. We identify a population-level response in mouse PCs that scales inversely with reach velocity, suggesting a candidate mechanism for anticipatory control to target limb endpoint. We next interrogate how such a response is generated by combining high-density neural recordings with closed-loop optogenetic stimulation of cerebellar mossy fiber afferents originating in the pontine nuclei during reach, using perturbation schedules reminiscent of classic adaptation paradigms. We found that reach kinematics and PC electrophysiology adapt to position-locked mossy fiber perturbations and exhibit aftereffects when stimulation is removed. Surprisingly, we observed partial adaptation to position-randomized stimulation schedules but no opposing aftereffect. A model that recapitulated these findings provided novel insight into how the cerebellum deciphers cause-and-effect relationships to adapt.

neuroscience↗

bioRxiv2020

QUANTIFICATION OF MOUSE REACH KINEMATICS AS A FOUNDATION FOR MECHANISTIC INTERROGATION OF MOTOR CONTROL

Mice use reaching movements to grasp and manipulate objects in their environment, similar to primates. Thus, many recent studies use mouse reach to uncover neural control mechanisms, but quantification of mouse reach kinematics remains lacking, limiting understanding. Here we implement several analytical frameworks, from basic kinematic relationships to statistical machine learning, to quantify mouse reach kinematics across freely-behaving and head-fixed conditions. Overall, we find that many canonical features of primate reaches are conserved in mice, with some notable differences. Our results highlight the decelerative phase of reach as important in driving successful outcome. Late-phase kinematic adjustments are yoked to mid-flight position and velocity of the limb, allowing dynamic correction of initial variability, with head-fixed reaches being less dependent on position. Furthermore, consecutive reaches exhibit positional error-correction but not hot-handedness, implying opponent regulation of motor variability. Overall, our results establish foundational mouse reach kinematics in the context of neuroscientific investigation.

neuroscience↗

bioRxiv2018

Graded and bidirectional control of real-time reach kinematics by the cerebellum

The rules governing the relationship between cerebellar output and movement production remain unknown despite the well-recognized importance of the cerebellum in motor learning and precision. In this study, we investigated how cerebellar output sculpts reach behavior in mice by manipulating neural activity in the anterior interposed nucleus (IntA) in closed-loop with ongoing behavior. Optogenetic modulation of cerebellar output revealed monotonically graded and bidirectional control of real-time reach velocity by IntA. Furthermore, kinematic effects were relatively context invariant, suggesting that cerebellar output summates with ongoing motor commands generated elsewhere throughout the reaching movement. These results characterize the relationship between cerebellar output modulation and reach behavior as a bidirectional and scalable kinematic command signal. Our findings illustrate how learned, predictive coding in the cerebellar cortex could be actuated through the cerebellar nuclei to contribute in real time to purposive motor control.

neuroscience↗