Glutamate release

…machinery is capable of releasing glutamate at such extreme frequencies but the molecular determinants and ultrastructural organization underlying this presynaptic efficiency have yet to be elucidated. In several synapse types, the actin cytoskeleton, which is dyna

TRIO is a high-risk gene for schizophrenia (SCZ) and autism spectrum disorder (ASD) also variants found in patients with bipolar disorder (BPD). TRIO regulates small-GTPases to control neuronal migration, synapse development and function. However, it remains unclear whether and how discrete TRIO variants differentially impact these neurodevelopmental events. Here, we use murine models to investigate heterozygous variants that impact TRIO catalytic activity and are linked to NDDs: (TRIO) +/K1431M (ASD), +/K1918X (SCZ), and +/M2145T (bipolar disorder, BPD). Heterozygosity for Trio variants impac

Major depressive disorder (MDD) is a disabling psychiatric disorder and a major cause of global health burden, affecting approximately 280 million people. Traditional antidepressants primarily target the monoaminergic system, have significant side effects and leave approximately 40% of patients unresponsive to treatment. Ketamine (KET) is a fast-acting antidepressant that transiently inhibits N-methyl-d-aspartate receptors (NMDARs) to produce its antidepressant effects. KET is rapidly metabolised to hydroxynorketamine (HNK), which reduces depressive behaviour in rodents. HNK has been shown to

…patch-clamp recording of evoked glutamatergic excitatory postsynaptic currents (eEPSCs) with the local stimulation of presynaptic axon to investigate the insulin (100 nM) effect on the paired-pulse plasticity at cultured hippocampal neurons under hypoinsulinemia (4 days insulin-free media incubation).At control normoinsuli

…This results in uncontrolled glutamate release and impaired uptake by astrocytes. However, the role of elevated extracellular glutamate concentrations in exacerbating metabolic stress remains unclear. To investigate glutamate dynamics in the extracellular space during the acute phase of energy deprivation, we utilized the green-fluorescent glutamate sensor SF-iGluSnFR1. Organotypic mouse brain slice cultures were transduced with synapsi

…role of piccolo, namely the effect on glutamate release and the involvement of calcium channel regulation, using cortico-hippocampal cell cultures from a novel condi

…processes, complement also modulates glutamate release from cortical presynaptic terminals (synaptosomes) and astrocytic processes (gliosomes), controlling excitatory transmission and synaptic strength in this brain region. In both particles, the complement-evoked glutamate release relied on glutamate transporters (EAAT1 and 2) working in the reverse mode.We extended our study to synaptosome

Calcium released from intracellular stores is critical for controlling cellular processes such as secretion, synaptic transmission, and gene expression. Ryanodine receptors (RyRs) are Ca2+-permeable channels found in the endoplasmic reticulum. Currently, the relationship between Ca2+-induced Ca2+release (CICR) via RyRs and Ca2+-dependent synaptic transmission is unclear. Here, we investigated the role and potential mechanisms of RyR-mediated Ca2+ release at excitatory synapses. Experiments were performed on mouse hippocampal autaptic neurons (hANs) and adrenal chromaffin cells (CCs). The analy

The cerebellum is an area of the brain involved in sensory-motor adaptation, movement coordination and higher cognitive processes. Within the cerebellar cortex, mossy fibres (MFs) convey sensorimotor input to a dense layer of granule cells (GrCs). GrCs relay this information through parallel fibre (PF) projections that synapse with Purkinje cells (PCs), the sole output of the cerebellar cortex, and molecular layer interneurons (MLI), which provide feedforward inhibition of PCs. Accordingly, PCs compute incoming sensorimotor patterns and send inhibitory outputs that rapidly adjust motor movemen

…visually evoked calcium activity and glutamate release from RGC boutons. Two-photon calcium imaging revealed that serotonin axon stimulation suppressed RGC boutons

Spike Timing Dependent Plasticity (STDP) is argued to modulate synaptic strength depending on the timing of pre- and postsynaptic spikes. Physiological experiments identified a variety of temporal kernels: Hebbian, anti-Hebbian and symmetrical LTP/LTD. In this work we present a novel plasticity model, the Voltage-Dependent Pathway Model (VDP), which is able to replicate those distinct kernel types and intermediate versions with varying LTP/LTD ratios and symmetry features. In addition, unlike previous models it retains these characteristics for different neuron models, which allows for compari

…Here, based on a detailed analysis of glutamate release from bipolar cells, we outline the rules that govern the representation of object motion in the early processing stages. Our main findings are as follows: (1) Motion processing begins already at the first retinal synapse. (2) The shape and the amplitude of motion responses cannot be reliably predicted from bipolar cell responses to stationary objects. (3) Enhanced representation of novel objects - particularly in bipo

Neocortical-hippocampal interactions during off-line periods such as slow-wave sleep are implicated in memory processing. In particular, recent memory traces are replayed in hippocampus during some sharp-wave ripple (SWR) events, and these replay events are positively correlated with neocortical memory trace reactivation. A prevalent model is that SWR arise ‘spontaneously’ in CA3 and propagate recent memory ‘indices’ outward to the neocortex to enable memory consolidation there; however, the spatiotemporal distribution of neocortical activation relative to SWR is incompletely understood. We us