Topic: motor coordination

Complex motor behaviors involve the precise coordination of different body parts. While motor coordination has been extensively studied in expert animals, the behavioral and neural processes involved in its emergence through learning are still not well understood. To answer this question, we combined longitudinal behavioral analyses with population recordings from the cerebellum, which is a key region for movement coordination and motor learning. We trained mice to walk on a motorized runged treadmill over multiple days while Ca2+-activity was recorded from cerebellar molecular layer interneur

Circadian clock gene expression in various midbrain areas plays a central role in the regulation of behavior, including reward-related processes, affective states, and motor functioning. Specifically, recent work has revealed a sex-specific effect of Bmal1 expression in the striatum on voluntary alcohol consumption in mice: suppression in males and augmentation in females. Interestingly, Bmal1 expression in the nucleus accumbens, a striatal subregion known for its role in mediating reward processes, inhibits alcohol consumption in both males and females, thus indicating that other striatal sub

Cirrhotic patients may show minimal hepatic encephalopathy (MHE), with mild cognitive impairment and motor deficits. Hyperammonemia and inflammation are the main contributors to the cognitive and motor alterations of MHE. Hyperammonemic rats reproduce these alterations. There are no specific treatments for the neurological alterations of MHE. Extracellular vesicles from mesenchymal stem cells (MSC-EVs) are promising to treat inflammatory and immune diseases.We aimed to assess whether treatment of hyperammonemic rats with MSC-EVs reduced neuroinflammation in cerebellum and restored motor coordi

The autosomal recessive mutation Gly483Glu, occurring spontaneously in the murine protein Herc1, leads to its overexpression in the cerebellum of the tambaleante mouse (tbl). This causes dysregulation of autophagy-mediated death of Purkinje cells (PC) from two months of age, along with dysregulation of the PI3K/AKT/mTOR signalling pathway responsible for proper axonal myelination. Both situations trigger the onset of an ataxic neuromuscular syndrome characterized by motor control impairments. In response to this disturbance, even before PC death occurs, microglia present in the cerebellum can

Anti-IgLON5 is a rare neurological disorder characterized by brainstem dysfunction, abnormal movements, sleep alterations, autoantibodies against IgLON5, and neurodegeneration, sometimes with neuronal deposits of tau. IgLON5 is a neural cell adhesion molecule of unknown function. This study was aimed to determine the effects of loss of function of IgLON5 in a Knockout (IgLON5-KO) mouse model assessing brain morphology, social behavior, and symptoms.IgLON5-KO mouse was produced by CRISPR-Cas9 technology. Two-month-old IgLON5-KO and wild-type mice were subjected to a comprehensive battery of beh

Cerebral ischemia is the result of reduced or interrupted blood flow to the brain. Cerebral ischemia is reversible or irreversible in the neurons of the affected area, and subsequent free radical damage can be exacerbated by reperfusion. Ciproxifan is used to study the involvement of histaminergic neurons in different phases such as wakefulness and cognition. We wanted to find out whether ciproxifan has a protective effect on the hippocampus of rats with cerebral ischemia-reperfusion injury.A total of 32 adult male rats were used for the experiment. Four cages were formed with randomly selecte

The lateral hypothalamus (LH) is emerging as a brain region of interest in Parkinson’s disease (PD). Specifically, the LH neuron populations have been shown to degenerate in PD, thus undergoing neuron loss like the substantia nigra (SN) which is a defining feature of PD that is thought to underlie observed motor symptoms. Interestingly, the LH has strong anatomical projections to the SN, but the behavioural functions associated with this projection have not been determined. We have recently shown that the LH is involved in habitual instrumental responding and spontaneous locomotor activity in

PCD mice suffer the postnatal death of cerebellar Purkinje neurons and mitral cells of the olfactory bulb (OB). They are also defective in IGF1, but little is known about other neurotrophic factors, which may act as neuroprotective molecules.The expression of different neurotrophic factors (IGF1, BDNF, VEGF-A and VEGF-B) was analyzed by qPCR and ELISA around cerebellar and bulbar degenerations of PCD mice. Then, we applied two different therapies depending on the affected region.1. We refined healthy bone marrow transplants to reduce the degeneration of mitral cells. PCD mice were transplanted

Val667Ile is a de novo variant discovered in the GRIN2D gene found to be associated with Developmental and Epileptic Encephalopathies (DEEs). DEEs are a group of devastating disorders that involve global developmental delay and epileptic abnormalities. Patients with this variant exhibit a range of cognitive and motoric impairments, including intractable epilepsy, intellectual disabilities, motor deficits and premature death. The market lacks suitable treatments that alleviate these symptoms, and available therapy is focused solely on the epileptic phenotype. Our aim is to find a therapy that t

The cerebellum is involved in motor coordination and is divided into anatomo-functional modules processing sensorimotor information from a given body part. This information is conveyed by mossy fibers to granule cells (GC) contacting Purkinje cells (PC) belonging to different modules via their long axons, the parallel fibers (PFs). PFs underlie inter-modular communication, which may be at the core of motor coordination. Therefore, the main goal of our research is to understand how intermodular communication in the cerebellar cortex underlies motor adaptation.Using patterned light photostimulat

GABAergic neurotransmission is enhanced in the cerebellum of hyperammonemic rats, an animal model of hepatic encephalopathy, and this induces motor incoordination. There is an interplay between neuroinflammation and GABAergic neurotransmission, but the underlying mechanisms remain unclear. This work aimed to unveil the molecular mechanisms by which GABAergic neurotransmission modulates neuroinflammation in the cerebellum.Ex-vivo experiments were performed using cerebellar slices from control and hyperammonemic rats treated or not with bicuculline. We analyzed by immunohistochemistry microglia

Aim: The intricate development of Parkinson's disease (PD) has posed a significant challenge in finding effective treatments. In the current study, a diaryl pyrrole compound, 1-(2-chlorophenyl)-2-methyl-5-(4-chlorophenyl)-1H-Pyrrole, was designed, synthesized, and tested for possible motor function improvement in 6-hydroxydopamine (6-OHDA) induced neurotoxicity in a rat model of PD.Method: Parkinsonism was triggered unilaterally by injecting 6-OHDA (12μg/4μl/rat) into the striatum. The compound (1,5,10 and 30 mg/kg) was then given intraperitoneally for 14 consecutive days following the 6-OHDA

The tottering mouse, which harbors a mutation in the CACNA1A gene encoding a P/Q-type voltage-gated calcium channel, serves as a robust tool in neuroscience research for investigating Epilepsy and Episodic Ataxia Type 2 (EA2). In this study, we characterized the tottering mouse phenotype by leveraging ex vivo (loose-cell) and in vivo (extracellular) electrophysiology recordings of Purkinje cells (PCs) within the cerebellum, along with behavioral tests. Our findings reveal that tottering mice display increased irregularity in action potential (AP) firing of PCs without a change in frequency, bu

Optimal mammalian brain function relies on well-organized neuronal networks. GABAergic inhibitory interneurons precisely target subcellular regions to modulate synaptic inhibition and influence the timing of different neural networks. However, the molecular mechanisms guiding the assembly and stability of inhibitory synapses remain largely undefined. In this study, we explored an extracellular signalling pathway that uphold synaptic inhibition at a central inhibitory synapse. Using the cerebellar basket cell to Purkinje cell connection as a model, we discovered an unconventional paracrine path