Search results for "Glutamatergic"
showing 10 items of 98 documents
Subventricular zone neural progenitors protect striatal neurons from glutamatergic excitotoxicity.
2012
The functional significance of adult neural stem and progenitor cells in hippocampal-dependent learning and memory has been well documented. Although adult neural stem and progenitor cells in the subventricular zone are known to migrate to, maintain and reorganize the olfactory bulb, it is less clear whether they are functionally required for other processes. Using a conditional transgenic mouse model, selective ablation of adult neural stem and progenitor cells in the subventricular zone induced a dramatic increase in morbidity and mortality of central nervous system disorders characterized by excitotoxicity-induced cell death accompanied by reactive inflammation, such as 4-aminopyridine-i…
Cannabinoid CB1 Receptor Calibrates Excitatory Synaptic Balance in the Mouse Hippocampus
2015
The endocannabinoid system negatively regulates the release of various neurotransmitters in an activity-dependent manner, thereby influencing the excitability of neuronal circuits. In the hippocampus, cannabinoid type 1 (CB1) receptor is present on both GABAergic and glutamatergic axon terminals. CB1 receptor-deficient mice were previously shown to have increased hippocampal long-term potentiation (LTP). In this study, we have investigated the consequences of cell-type-specific deletion of the CB1 receptor on the induction of hippocampal LTP and on CA1 pyramidal cell morphology. Deletion of CB1 receptor in GABAergic neurons in GABA-CB1-KO mice leads to a significantly decreased hippocampal …
Protective effects of mirtazapine in mice lacking the Mbnl2 gene in forebrain glutamatergic neurons: Relevance for myotonic dystrophy 1
2019
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by muscle weakness and wasting and by important central nervous system-related symptoms including impairments in executive functions, spatial abilities and increased anxiety and depression. The Mbnl2 gene has been implicated in several phenotypes consistent with DM1 neuropathology. In this study, we developed a tissue-specific knockout mouse model lacking the Mbnl2 gene in forebrain glutamatergic neurons to examine its specific contribution to the neurobiological perturbations related to DM1. We found that these mice exhibit long-term cognitive deficits and a depressive-like state associated with neuronal loss, increa…
Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission
2016
Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical respo…
Sub-chronic variable stress induces sex-specific effects on glutamatergic synapses in the nucleus accumbens
2017
Men and women manifest different symptoms of depression and under current diagnostic criteria, depression is twice as prevalent in woman. However, little is known of the mechanisms contributing to these important sex differences. Sub-chronic variable stress (SCVS), a rodent model of depression, induces depression-like behaviors in female mice only, modeling clinical evidence of higher susceptibility to mood disorders in women. Accumulating evidence indicates that altered neuroplasticity of excitatory synapses in the nucleus accumbens (NAc) is a key pathophysiological feature of susceptibility to social stress in males. Here we investigated the effects of SCVS on pre- and post-synaptic prote…
Age differences in the role of the cannabinoid type 1 receptor on glutamatergic neurons in habituation and spatial memory acquisition
2015
Abstract Aims Aging is typically linked with a decline in memory performance and alterations in neural integrity. In pathological aging such as Alzheimer's disease, these effects are aggravated. Studies using cannabinoid CB1 receptor-deficient mice have shown a role of the endocannabinoid system in memory processing and neuroprotection. As the CB1 receptor is expressed in various neuronal populations, in this study, we aimed at investigating the consequences of CB1 receptor gene inactivation in cortical glutamatergic neurons in mice (Glu-CB1-KO) in regard to age-related alterations in spatial memory performance. Main methods Juvenile (5.5–7.5 weeks), adult (5.5–7 months), and old (11.5–14 m…
Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (r)-(+)-[2,3-dihydro-5-methyl-3-(4-m…
2003
The aim of the present in vivo microdialysis study was to investigate whether prenatal exposure to the CB1 receptor agonist WIN55,212-2 mesylate (WIN; (R)-()-(2,3- dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo(1,2,3-de)- 1,4-benzoxazin-6-yl)-1-naphthalenylmethanone), at a dose of 0.5 mg/kg (s.c. from the fifth to the 20th day of gestation), that causes neither malformations nor overt signs of toxicity, influences cortical glutamate extracellular levels in adult (90- day old) rats. Dam weight gain, pregnancy length and litter size at birth were not significantly affected by prenatal treatment with WIN. Basal and K-evoked dialysate glutamate levels were lower in the cerebral cortex of adul…
Endocannabinoids render exploratory behaviour largely independent of the test aversiveness: role of glutamatergic transmission.
2009
To investigate the impact of averseness, controllability and familiarity of a test situation on the involvement of the endocannabinoid system in the regulation of exploratory behaviour, we tested conventional and conditional cannabinoid receptor type 1 (CB1)-deficient mice in behavioural paradigms with different emotional load, which depended on the strength of illumination and the ability of the animals to avoid the light stimulus. Complete CB1 null-mutant mice (Total-CB1-KO) showed an anxiogenic-like phenotype under circumstances where they were able to avoid the bright light such as the elevated plus-maze and the light/dark avoidance task. Conditional mutant mice lacking CB1 expression s…
A restricted population of CB1 cannabinoid receptors with neuroprotective activity.
2014
The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. Of note, CB1 receptors are expressed at the synapses of two opposing (i.e., GABAergic/inhibitory and glutamatergic/excitatory) neuronal populations, so the activation of one and/or another receptor population may conceivably evoke different effects. Despite the widely reported neuroprotective activity of the CB1 receptor in animal models, the precise pathophysiological relevance of those two CB1 receptor pools in neurodegenerative processes is unknown. Here, we first induced excitotoxic damage in the mouse brain b…
Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling.
2009
Cognitive impairment is one of the most important negative consequences associated with cannabis consumption. We found that CB1 cannabinoid receptor (CB1R) activation transiently modulated the mammalian target of rapamycin (mTOR)/p70S6K pathway and the protein synthesis machinery in the mouse hippocampus, which correlated with the amnesic properties of delta9-tetrahydrocannabinol (THC). In addition, non-amnesic doses of either the mTOR blocker rapamycin or the protein synthesis inhibitor anisomycin abrogated the amnesic-like effects of THC, pointing to a mechanism involving new protein synthesis. Moreover, using pharmacological and genetic tools, we found that THC long-term memory deficits …