Topic: glutamatergic synapses

Neuronal apoptosis is a mechanism used to clear the cells of oxidative stress or DNA damage and to refine the final number of neurons for a functional neuronal circuit. The tumour suppressor protein p53 is a key regulator of the cell cycle and serves as a checkpoint for eliminating neurons with high DNA damage, aberrant hyperproliferative signals or cellular stress. Meanwhile p53 is largely expressed in progenitors’ cells during development, in adult mice p53 expression is restricted to the neurogenic niches where it regulates cell proliferation and self-renewal. To investigate the functional

Autism is a complex and heterogeneous neurodevelopmental condition. One of the major pathophysiological alterations in this disorder is an excitatory/inhibitory (E/I) neurotransmission imbalance. However, the underlying mechanisms of this imbalance remain poorly understood. The neuromodulator nitric oxide (NO) constitutively participates in E/I activity regulation by interacting with both glutamate and GABA. Little is known about how nitrergic system works in the autistic brain, although several studies suggest that dysregulations in this system may be involved in the pathogenesis of autism.We

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Though available anticonvulsants achieve a full seizure control for two-thirds of the TLE patients, one third does not respond sufficiently to these drugs and resection of the seizure area is the best possible treatment for them. One way to improve this is to identify key regulatory ion channels in excitatory synaptic function. Here, we investigated the ultrastructural localization of I) P/Q-type voltage-gated calcium channels (Cav2.1) at the presynaptic site triggering vesicle release and II) AMPA receptors mediating the

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

In the olfactory system, the glomeruli of the olfactory bulb define the first synapse processing odour information in the brain. Here, many synapses are established between olfactory sensory neurons (OSNs) and olfactory bulb neurons. Xenopus tropicalis tadpoles provide an excellent experimental platform to investigate the molecular mechanisms of synaptic transmission in vivo due to its experimental accessibility and transparency. We investigated long-lasting depolarizations (LLDs) occurring in the glomerular layer of the olfactory bulb by measuring changes in the local field potential. We reco

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

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

Background: Prenatal alcohol exposure (PAE) induces a wide range of neurodevelopmental disabilities grouped under the term fetal alcohol spectrum disorders (FASD). The effects of PAE on brain development are dependent on complex long-lasting neurochemical events, including modification of glutamate receptors. Here, we explored whether PAE may affect the functional connectivity and, further, the molecular composition of the glutamatergic synapses in the prefrontal cortex (PFC) of adolescent mice and its effect on social behaviors.Methods: We generated an in vivo model of PAE, by exposing C57Bl/

Voltage-gated calcium channels (Cav) mediate calcium influx in living cells and are necessary for essential physiological functions such as muscle contraction and excitation-transcription coupling. Channels of the Cav2 family (Cav2.1, 2.2, and 2.3) are highly expressed in the central nervous system (CNS) and are important regulators of neuronal excitability. They are involved in pre- and postsynaptic functions where they, for example, trigger neurotransmitter release. Cav2.3 (α1E) is involved in neuronal development and, when compared to other α1 subunits, shows the strongest expression in mou

17-α-ethinyl estradiol (EE) is a semi-synthetic hormone and the main component of combined contraceptive pills and drugs with therapeutic indications such as hormone replacement therapy. In Europe and the USA, approximately sixty million women use oral contraceptives, and it is estimated that nearly two million unintended pregnancies occur each year due to medication errors, potentially exposing the embryo to EE during the first weeks of development. The hippocampus is a glutamatergic brain area expressing hormone receptors and hormones influence synaptogenesis. The development of glutamatergi