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Silent synapse

Marc Dinkin
Degeneration of neuron and axons following injury to cells with which they synapse is termed trans-synaptic degeneration. This phenomenon may be seen in postsynaptic neurons (anterograde) or in presynaptic neurons (retrograde). Retrograde trans-synaptic degeneration (RTSD) of the retinal ganglion cells and retinal nerve fiber layer following injury to the occipital lobe has been well documented histologically in animal studies, but its occurrence in the human retina was, for many years, felt to be limited to cases of neonatal injury during a critical period of neuronal development...
February 2017: Current Neurology and Neuroscience Reports
Marzena Stefaniuk, Anna Beroun, Tomasz Lebitko, Olga Markina, Szymon Leski, Ksenia Meyza, Anna Grzywacz, Jerzy Samochowiec, Agnieszka Samochowiec, Kasia Radwanska, Leszek Kaczmarek
BACKGROUND: Dysfunction of the glutamatergic system has been implicated in alcohol addiction; however, the molecular underpinnings of this phenomenon are still poorly understood. In the current study we have investigated the possible function of matrix metalloproteinase-9 (MMP-9) in alcohol addiction because this protein has recently emerged as an important regulator of excitatory synaptic plasticity. METHODS: For long-term studies of alcohol drinking in mice we used IntelliCages...
January 5, 2017: Biological Psychiatry
Kyung-Seok Han, Samuel F Cooke, Weifeng Xu
Experience-dependent synapse refinement is essential for functional optimization of neural circuits. However, how sensory experience sculpts excitatory synaptic transmission is poorly understood. Here, we show that despite substantial remodeling of synaptic connectivity, AMPAR-mediated synaptic transmission remains at equilibrium during the critical period in the mouse primary visual cortex. The maintenance of this equilibrium requires neurogranin (Ng), a postsynaptic calmodulin-binding protein important for synaptic plasticity...
January 24, 2017: Cell Reports
Kang K L Liu, Michael F Hagan, John E Lisman
Memory storage involves activity-dependent strengthening of synaptic transmission, a process termed long-term potentiation (LTP). The late phase of LTP is thought to encode long-term memory and involves structural processes that enlarge the synapse. Hence, understanding how synapse size is graded provides fundamental information about the information storage capability of synapses. Recent work using electron microscopy (EM) to quantify synapse dimensions has suggested that synapses may structurally encode as many as 26 functionally distinct states, which correspond to a series of proportionally spaced synapse sizes...
March 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Avani Shukla, Anna Beroun, Myrto Panopoulou, Peter A Neumann, Seth Gn Grant, M Foster Olive, Yan Dong, Oliver M Schlüter
Exposure to cocaine generates silent synapses in the nucleus accumbens (NAc), whose eventual unsilencing/maturation by recruitment of calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) after drug withdrawal results in profound remodeling of NAc neuro-circuits. Silent synapse-based NAc remodeling was shown to be critical for several drug-induced behaviors, but its role in acquisition and retention of the association between drug rewarding effects and drug-associated contexts has remained unclear. Here, we find that the postsynaptic proteins PSD-93, PSD-95, and SAP102 differentially regulate excitatory synapse properties in the NAc...
January 11, 2017: EMBO Journal
Heather L Smith, Jennifer N Bourne, Guan Cao, Michael A Chirillo, Linnaea E Ostroff, Deborah J Watson, Kristen M Harris
Mitochondria support synaptic transmission through production of ATP, sequestration of calcium, synthesis of glutamate, and other vital functions. Surprisingly, less than 50% of hippocampal CA1 presynaptic boutons contain mitochondria, raising the question of whether synapses without mitochondria can sustain changes in efficacy. To address this question, we analyzed synapses from postnatal day 15 (P15) and adult rat hippocampus that had undergone theta-burst stimulation to produce long-term potentiation (TBS-LTP) and compared them to control or no stimulation...
December 19, 2016: ELife
Jae Young Yoon, Sukwoo Choi
Silent synapses show NMDA receptor (NMDAR)-mediated synaptic responses, but not AMPAR-mediated synaptic responses. A prevailing hypothesis states that silent synapses contain NMDARs, but not AMPARs. However, alternative presynaptic hypotheses, according to which AMPARs are present at silent synapses, have been proposed; silent synapses show slow glutamate release via a fusion pore, and glutamate spillover from the neighboring synaptic terminals. Consistent with these presynaptic hypotheses, the peak glutamate concentrations at silent synapses have been estimated to be ≪170 μM, much lower than those seen at functional synapses...
January 22, 2017: Biochemical and Biophysical Research Communications
Jing Shen, Matthew T Colonnese
: A comprehensive developmental timeline of activity in the mouse cortex in vivo is lacking. Understanding the activity changes that accompany synapse and circuit formation is important to understand the mechanisms by which activity molds circuits and would help to identify critical checkpoints for normal development. To identify key principles of cortical activity maturation, we systematically tracked spontaneous and sensory-evoked activity with extracellular recordings of primary visual cortex (V1) in nonanesthetized mice...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Karin Buiting, Charles Williams, Bernhard Horsthemke
Angelman syndrome is a rare neurogenetic disorder that is characterized by microcephaly, severe intellectual deficit, speech impairment, epilepsy, EEG abnormalities, ataxic movements, tongue protrusion, paroxysms of laughter, abnormal sleep patterns, and hyperactivity. Angelman syndrome results from loss of function of the imprinted UBE3A (ubiquitin-protein ligase E3A) gene on chromosome 15q11.2-q13. This loss of function can be caused by a mutation on the maternal allele, a 5-7 Mb deletion of the maternally inherited chromosomal region, paternal uniparental disomy of chromosome 15, or an imprinting defect...
October 2016: Nature Reviews. Neurology
Ting-Ting Zhang, Feng-Yan Shen, Li-Qing Ma, Wen Wen, Bin Wang, Yuan-Zhi Peng, Zhi-Ru Wang, Xuan Zhao
Itch and pain share similar mechanisms. It has been well documented that the anterior cingulate cortex (ACC) is important for pain-related perception. ACC has also been approved to be a potential pruritus-associated brain region. However, the mechanism of sensitization in pruriceptive neurons in the ACC is not clear. In current study, a chronic itch model was established by diphenylcyclopropenone (DCP) application. We found that both the frequency and amplitude of miniature excitatory postsynaptic currents in the ACC were enhanced after the formation of chronic itch...
2016: Molecular Brain
Takashi Matsubara, Kuniaki Uehara
Homeostatic plasticity is considered to maintain activity in neuronal circuits within a functional range. In the absence of homeostatic plasticity neuronal activity is prone to be destabilized because Hebbian plasticity mechanisms induce positive feedback change. Several studies on homeostatic plasticity assumed the existence of a process for monitoring neuronal activity on a time scale of hours and adjusting synaptic efficacy by scaling up and down. However, the underlying mechanism still remains unclear. Excitatory synaptic efficacy is associated with the size of the dendritic spine, and dendritic spine size fluctuates even after neuronal activity is silenced...
2016: Frontiers in Neural Circuits
Rodrigo Martinez-Monedero, Chang Liu, Catherine Weisz, Pankhuri Vyas, Paul Albert Fuchs, Elisabeth Glowatzki
Mechanosensory hair cells release glutamate at ribbon synapses to excite postsynaptic afferent neurons, via AMPA-type ionotropic glutamate receptors (AMPARs). However, type II afferent neurons contacting outer hair cells in the mammalian cochlea were thought to differ in this respect, failing to show GluA immunolabeling and with many "ribbonless" afferent contacts. Here it is shown that antibodies to the AMPAR subunit GluA2 labeled afferent contacts below inner and outer hair cells in the rat cochlea, and that synaptic currents in type II afferents had AMPAR-specific pharmacology...
March 2016: ENeuro
Nicholas M Graziane, Shichao Sun, William J Wright, Daniel Jang, Zheng Liu, Yanhua H Huang, Eric J Nestler, Yu Tian Wang, Oliver M Schlüter, Yan Dong
Exposures to cocaine and morphine produce similar adaptations in nucleus accumbens (NAc)-based behaviors, yet produce very different adaptations at NAc excitatory synapses. In an effort to explain this paradox, we found that both drugs induced NMDA receptor-containing, AMPA receptor-silent excitatory synapses, albeit in distinct cell types through opposing cellular mechanisms. Cocaine selectively induced silent synapses in D1-type neurons, likely via a synaptogenesis process, whereas morphine induced silent synapses in D2-type neurons via internalization of AMPA receptors from pre-existing synapses...
July 2016: Nature Neuroscience
Natalia V Luchkina, Sarah K Coleman, Johanna Huupponen, Chunlin Cai, Anna Kivistö, Tomi Taira, Kari Keinänen, Sari E Lauri
Synaptic recruitment of AMPA receptors (AMPARs) represents a key postsynaptic mechanism driving functional development and maturation of glutamatergic synapses. At immature hippocampal synapses, PKA-driven synaptic insertion of GluA4 is the predominant mechanism for synaptic reinforcement. However, the physiological significance and molecular determinants of this developmentally restricted form of plasticity are not known. Here we show that PKA activation leads to insertion of GluA4 to synaptic sites with initially weak or silent AMPAR-mediated transmission...
January 2017: Neuropharmacology
Cristina V Dieni, Roberto Panichi, James B Aimone, Chay T Kuo, Jacques I Wadiche, Linda Overstreet-Wadiche
Persistent neurogenesis in the dentate gyrus produces immature neurons with high intrinsic excitability and low levels of inhibition that are predicted to be more broadly responsive to afferent activity than mature neurons. Mounting evidence suggests that these immature neurons are necessary for generating distinct neural representations of similar contexts, but it is unclear how broadly responsive neurons help distinguish between similar patterns of afferent activity. Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking...
April 20, 2016: Nature Communications
Suma Priya Sudarsana Devi, James R Howe, Céline Auger
KEY POINTS: Purkinje cells of the cerebellum receive ∼180,000 parallel fibre synapses, which have often been viewed as a homogeneous synaptic population and studied using single action potentials. Many parallel fibre synapses might be silent, however, and granule cells in vivo fire in bursts. Here, we used trains of stimuli to study parallel fibre inputs to Purkinje cells in rat cerebellar slices. Analysis of train EPSCs revealed two synaptic components, phase 1 and 2. Phase 1 is initially large and saturates rapidly, whereas phase 2 is initially small and facilitates throughout the train...
July 1, 2016: Journal of Physiology
Yao-Ying Ma, Xiusong Wang, Yanhua Huang, Helene Marie, Eric J Nestler, Oliver M Schlüter, Yan Dong
Environmental enrichment (EE) has long been postulated as a behavioral treatment for drug addiction based on its preventive effects in animal models: rodents experiencing prior EE exhibit increased resistance to establishing drug taking and seeking. However, the therapeutic effects of EE, namely, the effects of EE when applied after drug exposure, are often marginal and transient. Using incubation of cue-induced cocaine craving, a rat relapse model depicting progressive intensification of cocaine seeking after withdrawal from cocaine self-administration, our present study reveals that after cocaine withdrawal, in vivo circuit-specific long-term depression (LTD) unmasks the therapeutic power of EE to achieve long-lasting anti-relapse effects...
May 3, 2016: Proceedings of the National Academy of Sciences of the United States of America
Peter A Neumann, Yicun Wang, Yijin Yan, Yao Wang, Masago Ishikawa, Ranji Cui, Yanhua H Huang, Susan R Sesack, Oliver M Schlüter, Yan Dong
Exposure to cocaine induces addiction-associated behaviors partially through remodeling neurocircuits in the nucleus accumbens (NAc). The paraventricular nucleus of thalamus (PVT), which projects to the NAc monosynaptically, is activated by cocaine exposure and has been implicated in several cocaine-induced emotional and motivational states. Here we show that disrupting synaptic transmission of select PVT neurons with tetanus toxin activated via retrograde trans-synaptic transport of cre from NAc efferents decreased cocaine self-administration in rats...
August 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Franziska Greifzu, Daniel Parthier, Bianka Goetze, Oliver M Schlüter, Siegrid Löwel
Neuronal plasticity is essential to enable rehabilitation when the brain suffers from injury, such as following a stroke. One of the most established models to study cortical plasticity is ocular dominance (OD) plasticity in the primary visual cortex (V1) of the mammalian brain induced by monocular deprivation (MD). We have previously shown that OD-plasticity in adult mouse V1 is absent after a photothrombotic (PT) stroke lesion in the adjacent primary somatosensory cortex (S1). Exposing lesioned mice to conditions which reduce the inhibitory tone in V1, such as raising animals in an enriched environment or short-term dark exposure, preserved OD-plasticity after an S1-lesion...
2016: PloS One
Daniela B Pereira, Yvonne Schmitz, József Mészáros, Paolomi Merchant, Gang Hu, Shu Li, Adam Henke, José E Lizardi-Ortiz, Richard J Karpowicz, Travis J Morgenstern, Mark S Sonders, Ellen Kanter, Pamela C Rodriguez, Eugene V Mosharov, Dalibor Sames, David Sulzer
Neurotransmission at dopaminergic synapses has been studied with techniques that provide high temporal resolution, but cannot resolve individual synapses. To elucidate the spatial dynamics and heterogeneity of individual dopamine boutons, we developed fluorescent false neurotransmitter 200 (FFN200), a vesicular monoamine transporter 2 (VMAT2) substrate that selectively traces monoamine exocytosis in both neuronal cell culture and brain tissue. By monitoring electrically evoked Ca(2+) transients with GCaMP3 and FFN200 release simultaneously, we found that only a small fraction of dopamine boutons that exhibited Ca(2+) influx engaged in exocytosis, a result confirmed with activity-dependent loading of the endocytic probe FM1-43...
April 2016: Nature Neuroscience
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