Gait Analysis System - Locomotor Defect
Brain Structure and Function
Path integration is a navigation strategy that requires animals to integrate self-movements during exploration to determine their position in space. The medial entorhinal cortex (MEC) has been suggested to play a pivotal role in this process. Grid cells, head-direction cells, border cells as well as speed cells within the MEC collectively provide a dynamic representation of the animal position in space based on the integration of self-movements. All these cells are strongly modulated by theta oscillations, thus suggesting that theta rhythmicity in the MEC may be essential for integrating and coordinating self-movement information during navigation. In this study, we first show that excitotoxic MEC lesions, but not dorsal hippocampal lesions, impair the ability of rats to estimate linear distances based on self-movement information. Next, we report similar deficits following medial septum inactivation, which strongly impairs theta oscillations in the entorhinal–hippocampal circuits. Taken together, these findings demonstrate a major role of the MEC and MS in estimating distances to be traveled, and point to theta oscillations within the MEC as a neural mechanism responsible for the integration of information generated by linear self-displacements.
Journal of Psychopharmacology
Background: The substantial increase in use of 3,4-methylenedioxypyrovalerone (MDPV), a popular recreational synthetic cathinone, has raised legitimate questions about its behavioral consequences and abuse liability.
Aims: The aim of this study was to study MDPV-induced neurobehavioral effects in the rat, using different paradigms traditionally developed to study drug-attributed addictive properties.
Methods: Different patterns of intraperitoneal 3 mg/kg MDPV administration were investigated. Consequences on rat horizontal locomotion and behavior of acute, intermittent (once daily dosing over 10 days), and binge (three-time daily dosing for 3 days) MDPV administration as well as challenge after 10 day MDPV withdrawal were studied. The dopamine receptor-D1 antagonist, SCH23390, was bilaterally infused in the nucleus accumbens to determine the role of D1-receptors in MDPV-related effects on the associative memory recall using the conditioned place preference paradigm. In addition, in a separate experience using western blot, we investigated the effects of chronic MDPV administration (four injections during 24 h) on ΔFosB expression in the nucleus accumbens, caudate putamen, and prefrontal cortex.
Results: Acute MDPV administration increased stereotypies and open arm entries in the elevated plus maze while SCH23390 abolished MDPV-induced enhancing effects on memory consolidation. Intermittent MDPV administration resulted in sensitization of MDPV-induced locomotor effects and tolerance during the following challenge. With binge MDPV administration, locomotor activity was not altered despite tolerance onset after challenge. SCH23390 abolished MDPV-induced conditioned place preference. Chronic MDPV administration induced ΔFosB accumulation in the nucleus accumbens, caudate putamen, and prefrontal cortex.
Conclusions: Our findings clearly show that MDPV produces profound behavioral alterations mediated by the activation of the dopaminergic system similarly to other amphetamines.
Dysfunction of the mesencephalic locomotor region has been implicated in gait disorders. However, the role of its 2 components, the pedunculopontine and the cuneiform nuclei, in locomotion is poorly understood in primates.
To analyze the effect of cuneiform lesions on gait and balance in 2 monkeys and to compare them with those obtained after cholinergic pedunculopontine lesions in 4 monkeys and after lesions in both the cuneiform and pedunculopontine nuclei in 1 monkey.
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Motor disturbances strongly increase the burden of cocaine use disorder (CUDs). The objective of our translationalstudy was to identify the genes and biological pathways underlying the tolerance to cocaine-induced motor effects. Ina 5-day protocol measuring motor tolerance to cocaine in rats (N=40), modeling the motor response to cocaine inpatients, whole-genome RNA sequencing was conducted on the ventral and dorsal striatum to prioritize a geneticassociation study in 225 patients with severe CUD who underwent thorough phenotypic (cocaine-inducedhyperlocomotion, CIH; and cocaine-induced stereotypies, CIS) and genotypic [571,000 polymorphisms (SNPs)]characterization. We provide a comprehensive description of the rat striatal transcriptomic response to cocaine in ourparadigm. Repeated vs. acute cocaine binge administration elicited 27 differentially expressed genes in the ventralstriatum and two in the dorsal striatum. One gene,Lrp1b, was differentially expressed in both regions. In patients,LRP1Bwas significantly associated with both CIS and CIH. CIH was also associated withVPS13A, a gene involved in asevere neurological disorder characterized by hyperkinetic movements. TheLRP1Bminor allele rs7568970 had asignificant protective effect against CIS (558 SNPs, Bonferroni-correctedp=0.02) that resisted adjustment forconfounding factors, including the amount of cocaine use (adjusted beta=−0.965 and−2.35 for heterozygotes andhomozygotes, respectively,p< 0.01). Using hypothesis-free prioritization of candidate genes along with thoroughmethodology in both the preclinical and human analysis pipelines, we provide reliable evidence thatLRP1BandVPS13Aare involved in the motor tolerance to cocaine in CUD patients, in line with their known pathophysiology
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Major motor and gait deficits with sexual dimorphism in a Shank3 mutant mouse model
Contrasting findings were reported in several animal models with a Shank3 mutation used to induce various autism spectrum disorder (ASD) symptoms. Here, we aimed at investigating behavioral, cellular, and molecular consequences of a C-terminal (frameshift in exon 21) deletion in Shank3 protein in mice, a mutation that is also found in clinical conditions and which results in loss of major isoforms of Shank3. A special focus was made on cerebellar related parameters.
Link to the publication : https://link.springer.com/article/10.1186/s13229-020-00412-8
Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration
Spinal Cord Injury
Recovery from traumatic spinal cord injury (SCI) usually fails due to a cascade of cellular and molecular events that compromise neural tissue reconstitution by giving rise to glial scarring and cavity formation. We designed a scaffold material for SCI treatment containing only chitosan and water as fragmented physical hydrogel suspension (Chitosan-FPHS), with defined degree of acetylation (DA), polymer concentration, and mean fragment size. Implantation of Chitosan-FPHS alone into rat spinal cord immediately after a bilateral dorsal hemisection promoted reconstitution of spinal tissue and vasculature, and diminished fibrous glial scarring: with astrocyte processes primarily oriented towards the lesion, the border between lesion site and intact tissue became permissive for regrowth of numerous axons into, and for some even beyond the lesion site. Growing axons were myelinated or ensheathed by endogenous Schwann cells that migrated into the lesion site and whose survival was prolonged. Interestingly, Chitosan-FPHS also modulated the inflammatory response, and we suggest that this might contribute to tissue repair. Finally, this structural remodeling was associated with significant, long-lasting gain in locomotor function recovery. Because it effectively induces neural tissue repair, Chitosan-FPHS biomaterial may be a promising new approach to treat SCI, and a suitable substrate to combine with other strategies.