Biology subjects

Bowles, S.

Publications and source records attributed to Bowles, S..

3 recordsLinked to original sources

bioRxiv2024

The refinement paradox and cumulative cultural evolution: collective improvement in knowledge favors conformity, blind copying and hyper-credulity

Social learning is common in nature, yet cumulative culture (where knowledge and technology increase in complexity and diversity over time) appears restricted to humans. To understand why, we organized a computer tournament in which programmed entries specified when to learn new knowledge and when to refine (i.e. improve) existing knowledge. The tournament revealed a refinement paradox: refined behavior afforded higher payoffs as individuals converged on a small number of successful behavioral variants, but refining did not generally pay. Paradoxically, entries that refined only in certain conditions did best during behavioral improvement, while simple copying entries thrived when refinement levels were high. Cumulative cultural evolution may be rare in part because sophisticated strategies for improving knowledge and technology are initially advantageous, yet complex culture, once achieved, favors conformity, blind imitation and hyper-credulity.

evolutionary biology↗

bioRxiv2021

Vagus nerve stimulation accelerates motor learning through cholinergic modulation

Vagus nerve stimulation (VNS) is a neuromodulation therapy for a broad and rapidly expanding set of neurologic conditions. Classically used to treat epilepsy and depression, VNS has recently received FDA approval for stroke rehabilitation and is under preclinical and clinical investigation for other neurologic indications. Despite benefits across a diverse range of neurological disorders, the mechanism through which VNS influences central nervous system circuitry is not well described, limiting therapeutic optimization. A deeper understanding of the influence of VNS on neural circuits and activity is needed to maximize the use of VNS therapy across a broad range of neurologic conditions. To investigate how VNS can influence the neurons and circuits that underlie behavior, we paired VNS with upper limb movement in mice learning a skilled motor task. We leveraged genetic tools to perform optogenetic circuit dissection, as well as longitudinal in vivo imaging of calcium activity in cortical neurons to understand the effect of VNS on neural function. We found that VNS robustly enhanced motor learning when temporally paired with successful movement outcome, while randomly applied VNS impaired learning. This suggests that temporally-precise VNS may act through augmenting outcome cues, such as reinforcement signals. Within motor cortex, VNS paired with movement outcome selectively modulates the neural population that represents outcome, but not other movement-related neurons, across both acute and behaviorally-relevant timescales. Phasic cholinergic signaling from basal forebrain is required both for VNS-driven improvements in motor learning and the effects on neural activity in M1. These results indicate that VNS enhances motor learning through precisely-timed phasic cholinergic signaling to reinforce outcome, resulting in the recruitment of specific, behaviorally-relevant cortical circuits. A deeper understanding of the mechanisms of VNS on neurons, circuits and behavior provides new opportunities to optimize VNS to treat neurologic conditions.

neuroscience↗

bioRxiv2021

Closed-loop automated reaching apparatus (CLARA) for interrogating motor systems

Objective: Personalized neurostimulation is a rapidly expanding category of therapeutics for a broad range of indications. Development of these innovative neurological devices requires high-throughput systems for closed-loop stimulation of model organisms, while monitoring physiological signals and complex, naturalistic behaviors. To address this need, we developed CLARA, a closed-loop automated reaching apparatus. Approach: Using breakthroughs in computer vision, CLARA integrates fully-automated, markerless kinematic tracking of multiple features we use to classify animal behavior and precisely deliver neural stimulation based on behavioral outcomes. CLARA is compatible with advanced neurophysiological tools, enabling the testing of neurostimulation devices and identification of novel neurological biomarkers. Results: The CLARA system tracks unconstrained skilled reach behavior in 3D at 150hz without physical markers. The system fully automates trial initiation and pellet delivery and is capable of accurately delivering stimulation in response to trial outcome with sub-quarter second latency. Mice perform the skilled reach task in the CLARA system at a proficiency similar to manually trained animals. Kinematic data from the CLARA system provided novel insights into the dynamics of reach consistency over the course of learning, suggesting that changes are driven entirely by unsuccessful reach accuracy. Additionally, using the closed-loop capabilities of CLARA, we demonstrate that vagus nerve stimulation (VNS) delivered on reach success improves skilled reach performance and increases reach trajectory consistency in healthy animals. Significance: The CLARA system is the first mouse behavior apparatus that uses markerless pose tracking to provide real-time closed-loop stimulation in response to the outcome of an unconstrained motor task. Additionally, we demonstrate that the CLARA system was essential for our finding that VNS given after successful completion of a motor task improves performance in healthy animals. This approach has high translational relevance for developing neurostimulation technology based on complex human behavior.

neuroscience↗