Topic: GABAA receptor

Bergmann glia (BG) are radial glial cells in the cerebellar cortex that have multiple functions. They have been shown to interact with Purkinje cells in several ways: they modulate synaptic inputs to Purkinje cells, regulate excitability through external potassium concentration, and directly affect Purkinje cells through neurotransmitter release. In this study, we genetically expressed hM3Dq in BGs through GFAP-promoter-contained AAV virus. We showed that this BG-PC regulation is mediated by the NMDA receptor and GABAA receptor. Furthermore, using calcium imaging, we confirmed that BG activati

Pathogenic variants in GABAA receptor subunits are a prominent cause of genetic epilepsies. Recent biophysical analysis of pathogenic GABRB3 variants reveals that both loss- and gain-of-function can cause epilepsy. Stratification shows that patients carrying gain-of-function variants experience an earlier onset of seizures that are refractory and have worse developmental delay compared to loss-of-function variant patients. This suggests that distinct pathological mechanisms underlie disease in each GABRB3 functional class. To date, research has only focused on loss-of-function variants. Here,

Epilepsy is a chronic neurological disorder characterized by recurrent seizures. Despite the availability of many antiepileptic drugs (AEDs), 30% of the patients are resistant to standard therapies. GABAA receptor (GABAAR) expression and function are altered in the epileptic tissue, resulting in impaired inhibition and reduced sensitivity to GABAergic AEDs. Therefore, we are developing a gene therapy strategy for focal drug-resistant epilepsy based on the overexpression of specific GABAAR subunits in hippocampal excitatory neurons, aiming at increasing network inhibition and enhancing the effe

Parkinson’s disease (PD) affects more than 6 million people worldwide, and will affect more in coming decades. There are no drugs available for PD that alter progression of disease. Current symptomatic treatments provide limited relief and have side effects. Enhanced GABAergic neurotransmission contributes to Parkinson’s disease (PD) pathogenesis and to some motor and non-motor symptoms. In animal models, GABA levels are increased in substantia nigra pars compacta, leading to reduced expression of tyrosine hydroxylase (TH) in neurons which contributes to the behavioural deficits. The aim was t

KCC2 is a neuronal-specific chloride extruder that acts to maintain a low intraneuronal chloride concentration, which is critical for fast synaptic inhibition through the GABAA receptor channels. In both humans and mice, KCC2 encoding gene is translated into two isoforms (KCC2a and KCC2b) that differ in their N-terminal domain. While KCC2b is strongly upregulated after birth, KCC2a remains very weakly expressed even in mature neurons. Despite its low expression, KCC2a has been shown to be essential for respiratory behaviour at birth, but the specific function of KCC2a in mature neurons has not

Cajal-Retzius neurons (CRNs) are among the first-born neurons in the neocortex and are critically involved in cortical layering during their transient lifetime. The molecular mechanisms behind early death of CRNs are still unclear but apoptosis is regulated by neuronal activity. During early development, CRNs are embedded into immature circuits where they mostly receive GABAergic inputs. Through immunohistochemistry and high-resolution confocal imaging, we quantified GABAergic synapse localizations across cortical layers during development in early postnatal mice and compared the GABAergic pro

Social interaction is a dynamic process wherein individuals exert reciprocal influence on one another. This process encompasses diverse types of behaviors which are infrequently delineated and examined distinctly. Moreover, while the quest for the social brain has mainly focused on the cerebrum, recent evidence has unveiled the potential engagement of cerebellar mechanisms in the regulation of social interactions. In this light, we microinfused muscimol (a GABAa receptor agonist) or saline into the deep cerebellar nuclei (DCN) of mice and measured their social behaviors in a modified version o

Reversal learning, a form of cognitive flexibility disrupted in many brain disorders, involves switching from one response to another when the reward contingencies of the responses are reversed. The hippocampus, especially the ventral hippocampus (VH), connects to fronto-striatal circuits regulating reversal learning. Previous studies reported that hippocampal lesions impaired, whereas chemogenetic activation of VH facilitated, reversal learning acquisition in animal models. However, there is limited evidence on how VH activity affects distinct stages of reversal learning. Therefore, we examin