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Moreno-Lopez, Y.

Publications and source records attributed to Moreno-Lopez, Y..

3 recordsLinked to original sources

A Kinematic Deviation Index (KDI) for Evaluation of Forelimb Function in Rodents

Rodent models are widely used to study neurological conditions and assess forelimb movement to measure function performance, deficit, recovery and treatment effectiveness. Traditional assessment methods based on endpoints such as whether the task is accomplished, while easy to implement, provide limited information on movement patterns important to assess different functional strategies. On the other side, detailed kinematic analysis provides granular information on the movement patterns but is difficult to compare across laboratories, and may not translate to clinical metrics of upper limb function. To address these limitations, we developed and validated a kinematic deviation index (KDI) for rodents that mimics current trends in clinical research. The KDI is a unitless summary score that quantifies the difference between an animal movement during a task and its optimal performance derived from spatiotemporal marker sequences without pre-specifying movements. We demonstrate the utility of KDI in assessing reaching and grasping in mice and validate its discrimination between trial endpoints in healthy animals. Furthermore, we show KDI sensitivity to interventions, including acute and chronic spinal cord injury and optogenetic disruption of sensorimotor circuits. The KDI provides a comprehensive measure of motor function that bridges the gap between detailed kinematic analysis and simple success/failure metrics, offering a valuable tool for assessing recovery and compensation in rodent models of neurological disorders.

neuroscience↗

Refinement of corticospinal neuron activity during skilled motor learning

The learning of motor skills relies on plasticity of the primary motor cortex as task acquisition drives the remodeling of cortical motor networks1,2. Large scale cortical remodeling of evoked motor outputs occurs in response to the learning of skilled, corticospinal-dependent behavior, but not simple, unskilled tasks1. Here we determine the response of corticospinal neurons to both skilled and unskilled motor training and assess the role of corticospinal neuron activity in the execution of the trained behaviors. Using in vivo calcium imaging, we found temporal coding of corticospinal activity coincided with the development of skilled, but not unskilled, motor expertise. Animals that failed to learn our skilled, precision isometric pull task exhibited a limited repertoire of dynamic movements and reduced network modulation. Transection of the corticospinal tract and optogenetic regulation of corticospinal activity show the necessity for patterned corticospinal network activity in the execution of skilled, but not unskilled, movement. We reveal a critical role for corticospinal network modulation in the learning and execution of skilled motor movements. The integrity of the corticospinal tract is essential to the recovery of dexterous movement after central nervous system injuries and these findings should help to shape translational approaches to motor recovery.

neuroscience↗

Enhanced analgesic cholinergic tone after neuropathy

At the spinal cord level, a tone of endogenous acetylcholine (ACh) modulates nociceptive sensory processing. Increasing the level of spinal ACh induces analgesia in naive animals or in situation of acute pain in the clinics, but whether this is still the case in situations or models of chronic pain is controversial. Here, we demonstrate the persistence, and even increased impact of the analgesic cholinergic tone acting through nicotinic receptors in neuropathic mice. The neuropathy does not affect the number and properties of dorsal horn cholinergic neurons, proposed to be the source of spinal ACh. Subthreshold doses of acetylcholinesterase (AChE) inhibitors in sham animals become anti-allodynic in cuff mice suggesting that the alterations occur in the cholino-receptive neurons. Thus endogenous cholinergic signaling can be manipulated with low doses of drugs to relieve mechanical allodynia in animal neuropathy models. This opens new avenues with potentially fewer side effects for neuropathic pain treatment.

neuroscience↗