Neurotransmitter release

…of the presynaptic machinery for neurotransmitter release are transported and assembled focussing on our studies in genome-engineered human induced pluripotent st

The coupling of voltage-gated calcium channels (VGCCs) and vesicular calcium sensors for neurotransmitter release is crucial for fast and efficient synaptic transmission. At parallel fiber (PF)-Purkinje cell (PC) synapses in mouse cerebellum, the coupling tightens during synaptic maturation in parallel with switching of splicing isoforms of the P/Q-type VGCC (Cav2.1) EF-hand from EFb to EFa. The Cav2.1[EFa] isoform has been reported to have a tighter Ca2+ influx-sensor coupling distance than the Cav2.1[EFb] isoform in hippocampal pyramidal neurons. Thus, the shift in the splicing Cav2.1-EF han

…(STX1A) is known to regulate neurotransmitter release at pre-synaptic terminal. Previously, we found that some ASD patients were haploid for STX1A gene. We also reported that STX1A gene knockout mice (STX1A KO) showed unusual behavioral profiles similar to human ASD patient. Interestingly, the deficit of social recognition, one of the unusual behavior in STX1A KO, partially ameriolated with dopamine (DA) receptor agonis

Monocular deprivation-induced ocular dominance plasticity (MD-ODP) in the visual cortex is an established in vivo paradigm, in which inactivity-induced synaptic plasticity contributes to the functional reconfiguration of cortical networks. Bassoon (Bsn) is a presynaptic protein involved in the spatial and functional organisation of synaptic vesicle (SV) recycling. Here, we report a novel role for Bsn in the inactivity-induced functional reconfiguration of adult neocortical networks in vivo and in vitro. We subjected Bsn knock-out mice to MD and imaged visual stimulus-evoked intrinsic signals i

…crucial role in triggering synchronous neurotransmitter release. It is comprised of two key domains: the C2B domain, which requisitely binds intracellular calcium to facilitate vesicular fusion; and the C2A domain, which plays an auxiliary role in evoked exocytosis. Pathogenic C2B domain variants cause SYT1-associated neurodevelopmental disorder, a rare condition characterised by movement disorder, developmental delay and intellectual disability. Recently, a number of new pathogenic SYT1 variants have been identified. Thes

Besides its role in triggering fast neurotransmitter release, the protein Synaptotagmin-1 (Syt1) is also involved in the docking and priming process of synaptic vesicles (SVs) to the presynaptic active zone. Research indicates that Synaptotagmin-7 (Syt7) shares some functions with Syt1, but the specific mechanisms by which Syt7 exerts these functions are not well understood. To investigate the putative redundant role of Syt1/Syt7 in SV docking and priming we performed various experiments as high-pressure freezing and electron microscopy on hippocampal cultures, and electrophysiological recordi

The habenula is a phylogenetically conserved bilateral brain structure known to modulate negative emotions. Hemispheric asymmetry in cortical areas plays a key role in behavior and cognition. Although habenular asymmetry is prominent in several vertebrate species, there is little evidence for left-right asymmetry in the mammalian habenula. To investigate the asymmetry in synaptic transmission in the medial habenula (MHb) to the interpeduncular nucleus (IPN) pathway in mice, we performed targeted electrical stimulation of left or right MHb-derived axons in acute slices. We discovered that the p

…to measure membrane potential, neurotransmitter release, pH, or various cellular metabolites, such as ATP or cAMP. Due to the spectral characteristics of these tools, different assemblies of optical hardware are usually needed to reveal the full potential of various biosensors. In a

GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles at the presynaptic activ

…potentiation and depression of evoked neurotransmitter release, as well as strongly facilitated spontaneous release. These changes correlated with a nanosco

…by providing localized delivery of neurotransmitters. While various drug delivery approaches have been investigated, an efficient neurotransmitter-based neuronal stimulation at the nanoscale still remai

…plays critical roles in regulating neurotransmitter release at both excitatory and inhibitory synapses within the central nervous system. Synapsins contribute significantly to synaptic plasticity and maintain the delicate balance between excitatory and inhibitory synaptic transmission. Notably, mutations in synapsins genes have been identified in forms of epilepsy with or without ASD. Syn II has been shown to interact with the presynaptic calcium channel P/Q, but the functional

Neurotransmitter release relies on the regulated fusion of synaptic vesicles (SVs) that are tightly packed within the presynaptic bouton of neurons. The ability of SVs to dynamically recycle while remaining clustered at the presynapse is unknown but suggests anchoring mechanisms that regulate SV function. One potential anchor is a family of phosphoproteins that interact with presynaptic SVs, called synapsins. Synapsins tightly bind SVs and form biomolecular condensates via liquid-liquid phase separation which can potentially help trap SVs at the presynapse. An alternative model for synapsin’s

…channels located in the vicinity of release-ready synaptic vesicles docked at the presynaptic active zone. Ca2+ ions enter the presynaptic terminal and activate the vesicular Ca2+ sensor, thereby triggering neurotransmitter release. This whole process occurs on a timescale of a few milliseconds. In addition to fast, synchronous release, which keeps pace with action potentials, many synapses also exhibit delayed asynchronous release

Accurate and synchronous neurotransmitter release is essential for brain communication and occurs when neurotransmitter-containing synaptic vesicles (SVs) fuse to release their content in response to neuronal activity. Neurotransmission is sustained by the process of SV recycling, which generates SVs locally at the presynapse. Until relatively recently it was believed that most mutations in genes that were essential for SV recycling would be incompatible with life, due to this fundamental role. However, this is not the case, with mutations in essential genes for SV fusion, retrieval and recycl

CA3-CA1 synapses in the hippocampus are the initial locus of episodic memory. The action of acetylcholine alters cellular excitability, modifies neuronal networks, and triggers secondary signaling that directly affects long-term plasticity (LTP) (the cellular underpinning of memory). It is therefore considered a critical regulator of learning and memory in the brain. Its action via M4 metabotropic receptors in the presynaptic terminal of the CA3 neurons and M1 metabotropic receptors in the postsynaptic spines of CA1 neurons produce rich dynamics across multiple timescales. We developed a model