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Molkov, Y.

Publications and source records attributed to Molkov, Y..

4 recordsLinked to original sources

Optimal Practice Schedules in a Dual-Rate Model of Motor Adaptation, and Their Recovery by Reinforcement Learning

A clinician guiding a stroke patient through a 45-minute rehabilitation session, a coach planning a training day, a teacher choosing the order of practice problems, they all face the same question: "given everything practiced so far, what should the next trial be?" The motor-learning literature offers two coarse answers, blocked and interleaved ("random") practice, with a well-known dissociation, blocked practice gives faster acquisition but worse retention, while interleaved practice gives the opposite. We argue that this dissociation is not a fixed property of practice schedules but a shadow of a richer structure. In particular, for a learner whose memory has a fast shared component and slower context-specific components, the best schedule should be a function of the learners current internal state and the time remaining before the retention probe. We make this precise in a minimal two-context fast-slow learner model whose optimal schedules can be computed exactly for short sessions and approximated by a structured beam-search upper bound for longer ones. The optimal schedule is not blocked, not interleaved, and not a single rule; it is a family of schedules determined by how much retention is weighted relative to acquisition. The family has three regimes (alternating, mixed, blocked-with-late-correction) and for long sessions, the optimal schedule has an interpretable structure -- exploit one context, repair the neglected one, then interleave to lock in retention. We then investigate whether a reinforcement-learning teacher, observing only the learners actions and errors without access to their internal memory states, can learn these optimal policies from interaction alone. Comparing these learned policies against the exact optima, we show that a model-free agent (PPO) recovers the short-horizon schedules and the long-horizon block-repair-interleave motif in the intermediate regime, but the benchmark also exposes a sharp failure in the acquisition-dominated regime, where PPO collapses to pure blocking and misses a sparse terminal correction. A warm-start diagnostic shows this failure is a genuine metastability of policy gradients rather than a tuning artifact, with blocked-plus-switch and pure-blocked acting as competing attractors that PPO cannot stabilize between. A hyperparameter sweep over observation history reveals that the agent requires very little behavioral context to plan optimally, demonstrating that partial observability is not a major barrier to finding optimal practice schedules. Finally, we discuss the implications of our framework for motor adaptation and contextual interference, offering practical insights on how instructors can design finite practice sessions to favor long-term retention.

neuroscience↗

Ionic Mechanisms Underlying Bistability in Spinal Motoneurons: Insights from a Computational Model

Spinal motoneurons are the final output of spinal circuits that engage skeletal muscles to generate motor behaviors. Many motoneurons exhibit bistable behavior, alternating between a quiescent resting state and a self-sustained firing mode, classically attributed to plateau potentials driven by persistent inward currents. This intrinsic property is important for normal movement control, but can become dysregulated, causing motor function deficits, like spasticity. Here we use a conductance-based single-compartment model, together with mouse spinal slice recordings,to investigate the ionic interactions underlying motoneuron bistability. We show that synergistic interactions among high-voltage-activated L-type Ca2+ current (ICaL), calcium-induced calcium release (CICR) and the Ca2+-activated non-specific cation current (ICAN) constitute a minimal mechanistic core that produces plateau potentials and bistable firing. Within this framework, the persistent sodium current (INaP) promotes plateau generation, in contrast to the Ca2+-dependent K+ current (IKCa) which opposes it. These results delineate ionic dependencies at the level of interactions rather than spatial localisation and provide a tractable basis for interpreting altered motoneuron excitability in disease. Key PointsO_LIWe investigated how spinal motoneurons, critical for skeletal muscle control, exhibit bistability, switching between quiet and self-sustained firing. This property stabilizes motor functions like postural control, and its dysregulation contributes to disorders such as spasticity. Using a single-compartment computational model and mouse spinal slice recordings, we explored the ionic interactions driving bistability. C_LIO_LIOur findings reveal that a calcium-activated cation non-specific current and calcium-induced calcium release form a core mechanism supporting the plateau depolarization essential for bistable firing. Within this framework, the persistent sodium current facilitates plateau generation, while the calcium-dependent potassium current counteracts it. Pharmacological manipulations in slices yielded results consistent with these current roles. C_LIO_LIOur study delineates the ionic dependencies of motoneuron bistability based on interactions, not spatial location. This offers a concise framework for interpreting excitability changes observed in normal conditions and following spinal cord injury, providing valuable insights into motor function and neurological disorders. C_LI

neuroscience↗

Sensory Feedback and Central Neuronal Interactions in Mouse Locomotion

Locomotion is a complex process involving specific interactions between the central neural controller and the mechanical components of the system. The basic rhythmic activity generated by locomotor circuits in the spinal cord defines rhythmic limb movements and their central coordination. The operation of these circuits is modulated by sensory feedback from the limbs providing information about the state of the limbs and the body. However, the specific role and contribution of central interactions and sensory feedback in the control of locomotor gait and posture remain poorly understood. We use biomechanical data on quadrupedal locomotion in mice and recent findings on the organization of neural interactions within the spinal locomotor circuitry to create and analyze a tractable mathematical model of mouse locomotion. The model includes a simplified mechanical model of the mouse body with four limbs and a central controller composed of four rhythm generators, each operating as a state machine controlling the state of one limb. Feedback signals characterize the load and extension of each limb as well as postural stability (balance). We systematically investigate and compare several model versions and compare their behavior to existing experimental data on mouse locomotion. Our results highlight the specific roles of sensory feedback and some central propriospinal interactions between circuits controlling fore and hind limbs for speed-dependent gait expression. Our models suggest that postural imbalance feedback may be critically involved in the control of swing-to-stance transitions in each limb and the stabilization of walking direction.

systems biology↗

The role of Kölliker-Fuse nucleus in breathing variability

The Kolliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apneas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupneic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing. Key pointsThe Kolliker-Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modeling to explore different dynamical regimes of KF activity and their compatibility with experimental observations. By analyzing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide plausible hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.

neuroscience↗