Topic: GABAergic synapses

During early stages of Alzheimer’s disease (AD) gradual accumulation and aggregation of Aβ oligomers (AβO) occurs prior to cognitive decline. This preclinical stage of AD is further characterized by synaptic dysfunction and network hyperexcitability. We recently discovered that 24-hour treatment of AβO​​​​​ to hippocampal slices impairs release at GABAergic synapses, most prominently at dendritic inhibitory synapses. This suggests that inhibitory synapses are particularly vulnerable to AβO toxicity.We currently use advanced imaging approaches in vitro to further investigate the mechanisms that

Adult neurogenesis, the differentiation of new neurons from neural stem cells (NSCs), occurs primarily within the subventricular zone (SVZ) and the hippocampal dentate gyrus (DG). Caffeine, the most widely used psychostimulant, is a potent non-selective adenosine receptor antagonist. Though the adenosinergic system has been shown to regulate adult brain plasticity, caffeine impact on postnatal neurogenesis and synaptogenesis remains elusive. Thus, the main goal of this work was to dissect caffeine effects on the differentiation and maturation of postnatal NSCs into neurons.Our results indicate

Activation of group I metabotropic glutamate receptors (mGluR) in the brain mediates changes in neuronal excitability, synaptic transmission, and network activity of cortical circuits and has been linked to learning-related plasticity, brain state-modulation as well as various human neurological disorders but studies investigating their effect in human brain are scarce and mostly focused on excitatory neurons. We studied the effects of group I mGluR activation on monosynaptic glutamatergic synapses arriving onto interneurons and disynaptic GABAergic synapses using dual whole-cell patch clamp r

Autistic spectrum disorder (ASD) has been associated with genetic alterations of synaptic proteins such as the point mutation R451C in neuroligin 3 (NLGN3), a postsynaptic adhesion molecule located at both excitatory and inhibitory synapses. By exploiting the transgenic NLGN3-R451C knock-in (KI) mice, an animal model of ASD, we investigated this mutation in the coordination of excitatory and inhibitory synaptic plasticity. In hippocampal primary cultures, while the NLGN3-R451C protein was less expressed in KI mice with respect to WT, the molecular and functional properties of basal excitatory

Immunoglobulin superfamily member 9b (IgSF9b) is a cell adhesion protein that has been linked to the etiology of several psychiatric disorders, including bipolar disorder and schizophrenia. Based on previous studies in neuronal cultures, IgSF9b was proposed to specifically regulate the structure and function of GABAergic synapses in the brain through an indirect interaction with the synaptic adhesion protein Neuroligin-2. To date, however, very little is known about the expression pattern of IgSF9b in the intact brain, and the synaptic localization of IgSF9b in different brain regions has neve

Different neurological diseases are characterized by an imbalance between excitatory and inhibitory synapses, including epilepsy or autism spectrum disorders (ASD). One of many genes linked to these conditions is the scaffold protein neurobeachin (NBEA), which has been previously described as essential for receptor targeting to the plasma membrane. While its role at excitatory synapses has been studied extensively, NBEA function at inhibitory synapses is still barely understood. Here we report that NBEA is recruited to the GABAergic synapses in an activity-dependent manner and interacts with t

Adenosine acts as a fine regulator of synaptic plasticity in the adult brain. We showed a key role for the adenosine A2A receptor (A2AR) in the stabilization of nascent active GABAergic synapses during brain development (Gomez-Castro et al., Science 374 2021). Our data indicate that this regulation extends to glutamatergic synapses and involve neuroglial interactions. The suppression of neuronal A2AR with a shRNA approach in mixed neuron-glia cultures led to the loss of ~30% of glutamatergic synapses. Puzzlingly, activating A2AR in these cultures with a selective agonist (CGS21680) also led to