Topic: glutamatergic transmission

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

In human, genetic predispositions or deleterious environmental conditions may cause adverse effects on the developing brain. In preterm neonates, oligodendrocytes are particularly vulnerable and hypoxic conditions may result in white matter lesions leading to cerebral palsy and long-term disabilities. The glutamatergic transmission plays a critical role in the pathophysiology of these lesions but it is also a key actor involved in developmental mechanisms such as cell differentiation. Previous studies demonstrated a strong expression of the N-methyl-D-aspartate receptor by endothelial cells (e

Energy metabolism in the brain accounts for approximately 20% of the body’s oxygen consumption being glutamatergic transmission a major contributor. To meet these energetic requirements there is a tight coupling between neurons and astrocytes. Thus, neuronal glutamatergic activity decreases astrocytic oxidative glucose metabolism in favor of glucose metabolism to lactate. Lactate released by astrocytes can be oxidatively metabolized by neurons. However, little is known about the interplay between neuronal activity and astrocytic metabolism concerning other energetic sources. Here, we made use

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder diagnosed in presence of impaired social communication and interaction together with restricted, repetitive repertoire of behaviours, interests, and activities. To date, available medications address comorbidities (e.g. anxiety, irritability, seizures) rather than core symptoms. The aim of the present study was to explore the therapeutic potential of foliglurax, a mGlu4 positive allosteric modulator (PAM), in relieving ASD-like behavioral features in the well validated genetic Shank3B knockout mouse model, and to assess ho

Copy number variation in genes associated with glutamatergic transmission have emerged as significant factor in various mental and neurodegenerative disorders. Recent studies have shed light on the role of the GRIK4 gene, which encodes the GluK4 subunit of kainate receptors, in conditions such as autism and schizophrenia. Specifically, de novo duplications of the GRIK4 have been identified in individuals with autism. Overexpression of the Grik4 gene in a mouse model (GluK4over) leads to social deficits, anxiety and depression and has a significant impact on amygdala neuronal excitability, caus

Recent findings suggest that COMP360 (Compass Pathways’ investigational proprietary formulation of synthetic psilocybin) modulates negative affective biases in a rat model. Based on our current behavioural data, the mechanism is hypothesised to depend on psilocin, the active metabolite of psilocybin, acting as a partial agonist at both 5-HT2A and 5-HT1A receptors and altering neuronal activity, particularly in circuits which regulate affect and include the medial prefrontal cortex (mPFC). In the present study, we investigated effects of acute psilocin on stimulus-evoked excitatory postsynaptic

Sorting Nexin 27 (SNX27) is a hippocampal-enriched endosome-associated cargo adaptor that shapes endocytic events underlying neuronal function and excitability, being relevant for cognitive and reward-associated processes. There is an association of SNX27 with glutamatergic and dopaminergic signaling, as SNX27 modulation alters hippocampal glutamatergic transmission and dopaminergic neurons GABABR-activated GIRK signaling. Notwithstanding, the impact of SNX27 modulation on neuronal circuitry function or behavior remains elusive. In this work we deleted SNX27 in different neuronal types in orde

Synapsins are a family of synaptic vesicle phosphoproteins (SVs) playing a key role in synaptic transmission and neuronal development. Mutations of Syn genes lead to dysregulation in brain network functions implicated in the pathophysiology of neurological and psychiatric disorders. We aimed at investigating the impact of deletion of all three Syn isoforms on social and cognitive behavior in Syn triple knockout (TKO) mice and on the neuronal activity of the glutamatergic transmission in the infralimbic medial prefrontal cortex (IL-mPFC) and in hippocampal CA3 using in vivo electrophysiology. A