Medium spiny neurons

Major Depressive Disorder (MDD) is a prevalent, persistent and severe psychiatric condition characterized by persistent feelings of depression, anhedonia, and occasional suicidal thoughts, with stress identified as a major trigger. Previous research from our lab has shown changes in mouse emotional and cognitive behavior, and cellular and molecular alterations in some brain areas such as hippocampus, striatum and prefrontal cortex. Nevertheless, the mechanism underlying depression remain elusive, and so, an effective treatment. To tackle this issue, cannabidiol (CBD) treatment has emerged as a

Pre-clinical studies on drug addiction and relapse often overlooked volitional social interactions, which are of critical importance in human addiction. Recently, it has been demonstrated that social choice-based voluntary abstinence in rats attenuates the emergence of incubation of methamphetamine (Meth) craving relative to rats subjected to a forced abstinence. In the current study we investigated the molecular mechanisms by which social choice-based voluntary abstinence prevents the incubation of craving. An important mechanism driving cue-induced craving from psychostimulants in forced abs

…HD mainly targets the medium spiny neurons of the striatum and more broadly the corticostriatal pathway, but other brain areas, such as the hippocampus, are also affected at more advanced stages of the disease. These deregulations are responsible for a triad of symtoms, consisting in cognitive and psychiatric symptoms that occur prior to the

…GPR158 elevates evoked firing of NAc medium spiny neurons (MSNs), while activation of GPR158 in cholinergic i

Arginase 2 (Arg2), an arginine-metabolizing, mitochondrial enzyme, has been recently found to be enriched in the striatum, and progressive loss of Arg2 has been proposed as a potential factor contributing to the pathogenesis of Huntington’s disease (HD), a disorder primarily involving this region of the brain. Although direct metabolic role of Arg2 is well established, the importance of this enzyme for striatal function and dysfunction is not known. The purpose of this work was to identify cellular pathways potentially controlled by Arg2 in the striatum. In our experiments, we have used wild-t

Parkinson’s disease is caused by the selective loss of the dopaminergic neurons of the Substantia Nigra pars compacta and, consequently, striatal dopamine depletion. In Parkinson’s disease therapy, dopamine loss is counteracted by the administration of the dopamine precursor L-DOPA, which is initially effective in ameliorating motor symptoms, but over time it leads to a burdening side effect of uncontrollable jerky movements, termed L-DOPA-induced dyskinesia. To date, no efficient treatment for dyskinesia exists. The dopaminergic and serotonergic systems are intrinsically linked, and a role ha

…populations of concomitantly activated neurons defining drug-recruited ensembles. In this study, we explore the dynamics of recruitment of these ensembles through the encoding, strengthening and expression of cocaine-context associative memories. Additionally, we characterize the intrinsic (phenotypical) or acquired (plastic) cellular properties that

X-linked dystonia-parkinsonism (XDP) is a recessive neurodegenerative disease endemic to Panay, Philippines. The XDP striatum is notably reported to undergo significant atrophy, neuronal loss, and astrogliosis. However, detailed neuropathological studies characterising the human XDP striatum are limited.To advance our understanding of the human XDP striatum, immunohistochemistry coupled with automated analysis was conducted on post-mortem striatal tissue from 12 XDP and 5 age-matched neurologically normal cases to detail (1) the neurochemical architecture and (2) neuronal and glial populations

The nucleus accumbens (NAc), a central hub in reward processing, intricately modulates emotional behaviours, including anxiety. A compound derived from the metabolization of polyphenols by the microbiota, mitobooster (MB) has been previously shown to improve mitochondrial function by promoting turnover of the dysfunctional mitochondria. In this study, we aimed to understand the effect of MB treatment in outbred rats that show high anxious-like behaviour. First, animals were grouped by their trait anxiety based on the amount of time spent in the open arms in the elevated plus maze test, and the

The neurodegenerative process in Parkinson’s disease involves exacerbated inflammation with the participation of astrocytes. The P2Y1 receptor (P2Y1R) is a purinergic receptor predominantly expressed in astrocytes, regulating their activity, proliferation, and glutamate release. Therefore, our investigation explores whether the P2Y1R contributes to dopaminergic neuron degeneration, potentially via astrocytic involvement. To study dopaminergic degeneration, we injected 9 µg 6-hydroxydopamine into the right striatum (STR) of male Sprague-Dawley rats aged 6-8 weeks (ethical approval: 167/2019). D

…difference lying in caudate, with BD medium spiny neurons (MSNs) expressing significantly higher PDE5A, a cGMP-specific phosphodiesterase. Gene co-expression analysis (WGCNA) showed a strong

…iare striatal parvalbumin (PV) interneurons which exert a powerful feedforward inhibition on medium spiny neurons. To investigate the role of PV interneurons in regulating aberrant striatal activity observed in repetitive behaviors, we used the Sapap3 mutant mice, which exhibit excessive self-grooming. Using optogenetics activation of PV int

Kainate receptors are ionotropic glutamate receptors, involved in modulation of synaptic transmission in developing and adult brain. Genetic disruption of all five kainate receptor subunits reduces cortico-striatal synaptic connectivity and leads to OCD-related pathological behavior. The aim of the project is to evaluate if the OCD-like pathology arises due to the deficit in the development of cortico-striatal projections due to the lack of the kainate receptor subunit 1 (GluK1). We characterized the expression of GluK1 during the development of the cortico-striatal circuitry using immunohisto

…shown that besides GABA receptors, Medium Spiny Neurons (MSN), the projection neurons of the striatum, express functional chloride permeable GlyR, at adulthood, with α2 as the agonist bindin

…web of signaling pathways among its neurons. At the heart of this neural symphony is glutamatergic signaling.Glutamatergic control of striatal activity is essential for several brain functions.Abnormal glutamatergic signaling is associated with several pathological conditions including Huntington’s disease (HD), a rare neurological disease marked by striatal dysfunction and degeneration.Compromised retinoic acid receptor beta (RARβ) signaling observed in the striatum of HD patients and mice models has been suggested to critically contribu

…that predicts tuning of dopamine neurons to a quantity we call "action surprise," in addition to reward prediction error. In the same model, an implementation of learning from a motor efference copy also predicts a novel

…However, observed coactivation of neurons initiating the two pathways, striatal direct (dMSNs) and indirect (iMSNs) medium spiny neurons, has called this view into question. Here we study these circuits in mice performing an interval categorization task that requires a series of self-initiated and cued actions, and critically, a sustained period of dynamic action suppression. While movement produced similar activation of iMSNs and dMSNs in sensorimotor, dorsolateral

…Striatal medium spiny neurons (MSN) were classified based on the expression of dopamine D1 and D2 receptors. We implemented spike-timing dependent plasticity and structural parameters: i) the asymmetry of connections between MSN’s; and ii) the overlap between direct and indirect pathways. In action-selection simulations, we assume

…acting upon D1 and D2 receptors in medium spiny neurons (MSNs) of the striatum. At reported striatal dopamine levels, D1 and D2 receptors are mostl

Medium-spiny neurons (MSNs) in the striatum are required for interval timing, or the estimation of the time over several seconds via a motor response. We and others have shown that striatal MSNs can encode the duration of temporal intervals via time-dependent ramping activity, progressive monotonic changes in firing rate preceding behaviorally salient points in time. Here, we investigated how timing-related activity within striatal ensembles changes with experience. We leveraged a rodent-optimized interval timing task in which mice ‘switch’ response ports after an amount of time has passed