Biology subjects

Bichara, C.

Publications and source records attributed to Bichara, C..

4 recordsLinked to original sources

bioRxiv2022

Electrophysiological signatures reveal spinal learning mechanisms for a lasting sensorimotor adaptation

Neurocircuits within the spinal cord are essential for movement automaticity. However, spinal mechanisms that underlie lasting sensorimotor adjustments remain unclear. Here, we establish a quantitative kinematic framework to characterize a conditioning behavior in which spinal circuits without brain input learn to adapt motor output upon multimodal sensory integration, undergo extinction, and reinforcement of learned behavior with repetitive training. In-vivo Neuropixel spinal cord recordings from awake behaving mice reveal learning phase-tuned single unit activities. In addition, optically identified unit recordings and a loss-of-function experiment demonstrate an essential function of a class of spinal inhibitory interneurons in this learning paradigm. Together, these data reveal neuronal underpinnings that shape lasting sensorimotor adaptation where stable sensory dissemination regulates learning and the existence of neuronal assembly that retains learned behavior.

neuroscience↗

bioRxiv2020

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↗

bioRxiv2020

Sensory gating precedes motor command in evolution of the corticospinal tract

It is generally assumed that the main function of the corticospinal tract (CST) is to convey motor commands to bulbar or spinal motoneurons. Yet the CST has also been shown to modulate sensory signals at their entry point in the spinal cord, through presynaptic inhibition. By sequentially investigating different routes of corticofugal pathways through electrophysiological recordings and an intersectional viral strategy, we here demonstrate that motor and sensory modulation commands in mice belong to segregated paths within the CST. Sensory modulation is excuted exclusively by the CST via a population of lumbar interneurons located in the deep dorsal horn. In contrast, the cortex conveys the motor command via a relay in the upper spinal cord or supraspinal motor centers. At lumbar level, the main role of the CST is thus the modulation of sensory inputs, which is an essential component of the selective tuning of sensory feedback, to ensure well-coordinated and skilled movement. Impact statementWhile the corticospinal tract is often considered exclusively as a motor path, this study demonstrates that, in the mouse lumbar cord, its main role is the modulation of sensory inputs.

neuroscience↗

bioRxiv2019

Absence of subcerebral projection neurons delays disease onset and extends survival in a mouse model of ALS

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease of adulthood that affects voluntary motricity and rapidly leads to full paralysis and death. ALS arises from the combined degeneration of motoneurons in the spinal cord and brain stem, responsible for muscle denervation, and corticospinal projection neurons (CSN), responsible for emergence of the upper motor neuron syndrome. Recent studies carried on ALS patients suggest that the disease may initiate in the motor cortex and spread to its projection targets. However, this "corticofugal hypothesis" of ALS has not yet been specifically challenged. Here, we provide a direct test of this hypothesis by genetically removing subcerebral projection neurons (SubCerPN), including CSN, in Sod1G86R mice, a mouse model of ALS. Ablation of the transcription factor Fezf2, leading to the complete absence of all SubCerPN, delays disease onset, reduces weight loss and motor impairment, and increases survival without modifying disease duration. Importantly absence of SubCerPN and CSN also limits pre-symptomatic hyperreflexia. Together, our results demonstrate that major corticofugal tracts are critical to ALS onset, and that SubCerPN and CSN in particular may carry detrimental signals to their downstream targets. In its whole, this study provides first experimental arguments in favour of the corticofugal hypothesis of ALS.

neuroscience↗