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Frontiers in Synaptic Neuroscience

Graham C R Ellis-Davies
Two-photon microscopy produces the excited singlet state of a chromophore with wavelengths approximately double that used for normal excitation. Two photons are absorbed almost simultaneously, via a virtual state, and this makes the excitation technique inherently non-linear. It requires ultra-fast lasers to deliver the high flux density needed to access intrinsically very short lived intermediates, and in combination with lenses of high numerical aperture, this confines axial excitation highly. Since the two-photon excitation volume is similar to a large spine head, the technique has been widely used to study glutamatergic transmission in brain slices...
2018: Frontiers in Synaptic Neuroscience
Olivier Camiré, Ivan Lazarevich, Tommy Gilbert, Lisa Topolnik
In fast-spiking (FS), parvalbumin-expressing interneurons of the CA1 hippocampus, activation of the GluA2-lacking Ca2+ -permeable AMPA receptors (CP-AMPARs) in basal dendrites is coupled to Ca2+ -induced Ca2+ -release (CICR), and can result in a supralinear summation of postsynaptic Ca2+ -transients (post-CaTs). While this mechanism is important in controlling the direction of long-term plasticity, it is still unknown whether it can operate at all excitatory synapses converging onto FS cells or at a set of synapses receiving a particular input...
2018: Frontiers in Synaptic Neuroscience
Caroline A Browne, Robert Hammack, Irwin Lucki
Clinical and preclinical evidence implicates hyperexcitability of the lateral habenula (LHb) in the development of psychiatric disorders including major depressive disorder (MDD). This discrete epithalamic nucleus acts as a relay hub linking forebrain limbic structures with midbrain aminergic centers. Central to reward processing, learning and goal directed behavior, the LHb has emerged as a critical regulator of the behaviors that are impaired in depression. Stress-induced activation of the LHb produces depressive- and anxiety-like behaviors, anhedonia and aversion in preclinical studies...
2018: Frontiers in Synaptic Neuroscience
Melissa A Herman, Thorsten Trimbuch, Christian Rosenmund
Synaptic transmission requires the presynaptic release of neurotransmitter from synaptic vesicles (SVs) onto the postsynaptic neuron. Vesicular neurotransmitter transporter proteins, which use a V-ATPase-generated proton gradient, play a crucial role in packaging neurotransmitter into SVs. Recent work has revealed different proton dynamics in SVs expressing the vesicular glutamate transporter (VGLUT) or the vesicular GABA transporter (VGAT) proteins. At the whole synapse level, this results in different steady-state pH and different reacidification dynamics during SV recycling (Egashira et al...
2018: Frontiers in Synaptic Neuroscience
Sara Mederos, Candela González-Arias, Gertrudis Perea
Research on glial cells over the past 30 years has confirmed the critical role of astrocytes in pathophysiological brain states. However, most of our knowledge about astrocyte physiology and of the interactions between astrocytes and neurons is based on the premises that astrocytes constitute a homogeneous cell type, without considering the particular properties of the circuits or brain nuclei in which the astrocytes are located. Therefore, we argue that more-sophisticated experiments are required to elucidate the specific features of astrocytes in different brain regions, and even within different layers of a particular circuit...
2018: Frontiers in Synaptic Neuroscience
Pavlos Rigas, Charalambos Sigalas, Maria Nikita, Ani Kaplanian, Konstantinos Armaos, Leonidas Jordan Leontiadis, Christos Zlatanos, Aspasia Kapogiannatou, Charoula Peta, Anna Katri, Irini Skaliora
Understanding the long term impact of early life seizures (ELS) is of vital importance both for researchers and clinicians. Most experimental studies of how seizures affect the developing brain have drawn their conclusions based on changes detected at the cellular or behavioral level, rather than on intermediate levels of analysis, such as the physiology of neuronal networks. Neurons work as part of networks and network dynamics integrate the function of molecules, cells and synapses in the emergent properties of brain circuits that reflect the balance of excitation and inhibition in the brain...
2018: Frontiers in Synaptic Neuroscience
Pojeong Park, Heather Kang, Thomas M Sanderson, Zuner A Bortolotto, John Georgiou, Min Zhuo, Bong-Kiun Kaang, Graham L Collingridge
Long-term potentiation (LTP) at hippocampal CA1 synapses is classically triggered by the synaptic activation of NMDA receptors (NMDARs). More recently, it has been shown that calcium-permeable (CP) AMPA receptors (AMPARs) can also trigger synaptic plasticity at these synapses. Here, we review this literature with a focus on recent evidence that CP-AMPARs are critical for the induction of the protein kinase A (PKA)- and protein synthesis-dependent component of LTP.
2018: Frontiers in Synaptic Neuroscience
Karin R Aubrey, Stéphane Supplisson
The corelease of several neurotransmitters from a single synaptic vesicle has been observed at many central synapses. Nevertheless, the signaling synergy offered by cotransmission and the mechanisms that maintain the optimal release and detection of neurotransmitters at mixed synapses remain poorly understood, thus limiting our ability to interpret changes in synaptic signaling and identify molecules important for plasticity. In the brainstem and spinal cord, GABA and glycine cotransmission is facilitated by a shared vesicular transporter VIAAT (also named VGAT), and occurs at many immature inhibitory synapses...
2018: Frontiers in Synaptic Neuroscience
Feng Cao, Zikai Zhou, Sammy Cai, Wei Xie, Zhengping Jia
The GluA2 subunit of AMPA glutamate receptors (AMPARs) has been shown to be critical for the expression of NMDA receptor (NMDAR)-dependent long-term depression (LTD). However, in young GluA2 knockout (KO) mice, this form of LTD can still be induced in the hippocampus, suggesting that LTD mechanisms may be modified in the presence of GluA2-lacking, Ca2+ permeable AMPARs. In this study, we examined LTD at the CA1 synapse in GluA2 KO mice by using several well-established inhibitory peptides known to block LTD in wild type (WT) rodents...
2018: Frontiers in Synaptic Neuroscience
Andrew F Scheyer, Daniel T Christian, Marina E Wolf, Kuei Y Tseng
Extended-access cocaine self-administration induces a progressive intensification of cue-induced drug craving during withdrawal termed "incubation of cocaine craving". Rats evaluated after >1 month of withdrawal (when incubation of craving is robust) display alterations in excitatory synapses onto medium spiny neurons (MSNs) of the nucleus accumbens (NAc), including elevated levels of Ca2+ -permeable AMPA receptors (CP-AMPAR) and a transition from group I metabotropic glutamate receptor (mGluR) mGlu5- to mGlu1-mediated synaptic depression...
2018: Frontiers in Synaptic Neuroscience
Ryan D Shepard, Ludovic D Langlois, Caroline A Browne, Aylar Berenji, Irwin Lucki, Fereshteh S Nugent
Mounting evidence suggests that the long-term effects of adverse early life stressors on vulnerability to drug addiction and mood disorders are related to dysfunction of brain monoaminergic signaling in reward circuits. Recently, there has been a growing interest in the lateral habenula (LHb) as LHb dysfunction is linked to the development of mental health disorders through monoaminergic dysregulation within brain reward/motivational circuits and may represent a critical target for novel anti-depressants, such as ketamine...
2018: Frontiers in Synaptic Neuroscience
Johanna Buechler, Patricia C Salinas
Synapse dysfunction and loss represent critical early events in the pathophysiology of Alzheimer's disease (AD). While extensive research has elucidated the direct synaptotoxic effects of Amyloid-β (Aβ) oligomers, less is known about how signaling pathways at the synapse are affected by Aβ. A better understanding of the cellular and molecular mechanisms underlying synaptic vulnerability in AD is key to illuminating the determinants of AD susceptibility and will unveil novel therapeutic avenues. Canonical Wnt signaling through the Wnt co-receptor LRP6 has a critical role in maintaining the structural and functional integrity of synaptic connections in the adult brain...
2018: Frontiers in Synaptic Neuroscience
Qing Cheng, Sang-Ho Song, George J Augustine
We used genetic and pharmacological approaches to identify the signaling pathways involved in augmentation and potentiation, two forms of activity dependent, short-term synaptic plasticity that enhance neurotransmitter release. Trains of presynaptic action potentials produced a robust increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs). Following the end of the stimulus, mEPSC frequency followed a bi-exponential decay back to basal levels. The time constants of decay identified these two exponential components as the decay of augmentation and potentiation, respectively...
2018: Frontiers in Synaptic Neuroscience
Lennart Brodin, Oleg Shupliakov
The retromer complex mediates export of select transmembrane proteins from endosomes to the trans-Golgi network (TGN) or to the plasma membrane. Dysfunction of retromer has been linked with slowly progressing neurodegenerative disorders, including Alzheimer's and Parkinson's disease (AD and PD). As these disorders affect synapses it is of key importance to clarify the function of retromer-dependent protein trafficking pathways in pre- and postsynaptic compartments. Here we discuss recent insights into the roles of retromer in the trafficking of synaptic vesicle proteins, neurotransmitter receptors and other synaptic proteins...
2018: Frontiers in Synaptic Neuroscience
Antonella Pirone, Jonathan M Alexander, Jenny B Koenig, Denise R Cook-Snyder, Medha Palnati, Robert J Wickham, Lillian Eden, Neha Shrestha, Leon Reijmers, Thomas Biederer, Klaus A Miczek, Chris G Dulla, Michele H Jacob
Autism spectrum disorder (ASD) is a highly prevalent and genetically heterogeneous brain disorder. Developing effective therapeutic interventions requires knowledge of the brain regions that malfunction and how they malfunction during ASD-relevant behaviors. Our study provides insights into brain regions activated by a novel social stimulus and how the activation pattern differs between mice that display autism-like disabilities and control littermates. Adenomatous polyposis coli (APC) conditional knockout (cKO) mice display reduced social interest, increased repetitive behaviors and dysfunction of the β-catenin pathway, a convergent target of numerous ASD-linked human genes...
2018: Frontiers in Synaptic Neuroscience
Txomin Lalanne, Julia Oyrer, Mark Farrant, P Jesper Sjöström
Calcium-permeable (CP) AMPA-type glutamate receptors (AMPARs) are known to mediate synaptic plasticity in several different interneuron (IN) types. Recent evidence suggests that CP-AMPARs are synapse-specifically expressed at excitatory connections onto a subset of IN types in hippocampus and neocortex. For example, CP-AMPARs are found at connections from pyramidal cells (PCs) to basket cells (BCs), but not to Martinotti cells (MCs). This synapse type-specific expression of CP-AMPARs suggests that synaptic dynamics as well as learning rules are differentially implemented in local circuits and has important implications not just in health but also in disease states such as epilepsy...
2018: Frontiers in Synaptic Neuroscience
Ludovic D Langlois, Matthieu Dacher, Fereshteh S Nugent
One of the most influential synaptic learning rules explored in the past decades is activity dependent spike-timing-dependent plasticity (STDP). In STDP, synapses are either potentiated or depressed based on the order of pre- and postsynaptic neuronal activation within narrow, milliseconds-long, time intervals. STDP is subject to neuromodulation by dopamine (DA), a potent neurotransmitter that significantly impacts synaptic plasticity and reward-related behavioral learning. Previously, we demonstrated that GABAergic synapses onto ventral tegmental area (VTA) DA neurons are able to express STDP (Kodangattil et al...
2018: Frontiers in Synaptic Neuroscience
Chen Zhang, Jaewon Ko
No abstract text is available yet for this article.
2018: Frontiers in Synaptic Neuroscience
Tatiana V Lipina, Nikolay A Beregovoy, Alina A Tkachenko, Ekaterina S Petrova, Marina V Starostina, Qiang Zhou, Shupeng Li
Both Disrupted-In-Schizophrenia-1 (DISC1) and dopamine receptors D2R have significant contributions to the pathogenesis of schizophrenia. Our previous study demonstrated that DISC1 binds to D2R and such protein-protein interaction is enhanced in patients with schizophrenia and Disc1-L100P mouse model of schizophrenia (Su et al., 2014). By uncoupling DISC1 × D2R interaction (trans-activator of transcription (TAT)-D2pep), the synthesized TAT-peptide elicited antipsychotic-like effects in pharmacological and genetic animal models, without motor side effects as tardive dyskinesia commonly seen with typical antipsychotic drugs (APDs), indicating that the potential of TAT-D2pep of becoming a new APD...
2018: Frontiers in Synaptic Neuroscience
Yoshihisa Nakahata, Ryohei Yasuda
Dendritic spines are small protrusive structures on dendritic surfaces, and function as postsynaptic compartments for excitatory synapses. Plasticity of spine structure is associated with many forms of long-term neuronal plasticity, learning and memory. Inside these small dendritic compartments, biochemical states and protein-protein interactions are dynamically modulated by synaptic activity, leading to the regulation of protein synthesis and reorganization of cytoskeletal architecture. This in turn causes plasticity of structure and function of the spine...
2018: Frontiers in Synaptic Neuroscience
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