Search results for "Synaptic transmission."
showing 10 items of 178 documents
Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles
2019
Most aspects of nervous system development and function rely on the continuous crosstalk between neurons and the variegated universe of non-neuronal cells surrounding them. The most extraordinary property of this cellular community is its ability to undergo adaptive modifications in response to environmental cues originating from inside or outside the body. Such ability, known as neuronal plasticity, allows long-lasting modifications of the strength, composition and efficacy of the connections between neurons, which constitutes the biochemical base for learning and memory. Nerve cells communicate with each other through both wiring (synaptic) and volume transmission of signals. It is by now…
Auxiliary α2δ1 and α2δ3 Subunits of Calcium Channels Drive Excitatory and Inhibitory Neuronal Network Development
2020
VGCCs are multisubunit complexes that play a crucial role in neuronal signaling. Auxiliary α2δ subunits of VGCCs modulate trafficking and biophysical properties of the pore-forming α1 subunit and trigger excitatory synaptogenesis. Alterations in the expression level of α2δ subunits were implicated in several syndromes and diseases, including chronic neuropathic pain, autism, and epilepsy. However, the contribution of distinct α2δ subunits to excitatory/inhibitory imbalance and aberrant network connectivity characteristic for these pathologic conditions remains unclear. Here, we show that α2δ1 overexpression enhances spontaneous neuronal network activity in developing and mature cultures of …
Asymmetry Between Pre- and Postsynaptic Transient Nanodomains Shapes Neuronal Communication.
2020
Synaptic transmission and plasticity are shaped by the dynamic reorganization of signaling molecules within pre- and postsynaptic compartments. The nanoscale organization of key effector molecules has been revealed by single-particle trajectory (SPT) methods. Interestingly, this nanoscale organization is highly heterogeneous. For example, presynaptic voltage-gated calcium channels (VGCCs) and postsynaptic ligand-gated ion channels such as AMPA receptors (AMPARs) are organized into so-called nanodomains where individual molecules are only transiently trapped. These pre- and postsynaptic nanodomains are characterized by a high density of molecules but differ in their molecular organization an…
Chronic hyperammonemia alters extracellular glutamate, glutamine and GABA and membrane expression of their transporters in rat cerebellum. Modulation…
2018
Trafficking of glutamate, glutamine and GABA between astrocytes and neurons is essential to maintain proper neurotransmission. Chronic hyperammonemia alters neurotransmission and cognitive function. The aims of this work were to analyze in cerebellum of rats the effects of chronic hyperammonemia on: a) extracellular glutamate, glutamine and GABA concentrations; b) membrane expression of glutamate, glutamine and GABA transporters; c) how they are modulated by extracellular cGMP. Hyperammonemic rats show increased levels of extracellular glutamate, glutamine, GABA and citrulline in cerebellum in vivo. Hyperammonemic rats show: a) increased membrane expression of the astrocytic glutamine trans…
Astrocyte sodium signaling and the regulation of neurotransmission.
2015
The transmembrane Na(+) concentration gradient is an important source of energy required not only to enable the generation of action potentials in excitable cells, but also for various transmembrane transporters both in excitable and non-excitable cells, like astrocytes. One of the vital functions of astrocytes in the central nervous system (CNS) is to regulate neurotransmitter concentrations in the extracellular space. Most neurotransmitters in the CNS are removed from the extracellular space by Na(+) -dependent neurotransmitter transporters (NeuTs) expressed both in neurons and astrocytes. Neuronal NeuTs control mainly phasic synaptic transmission, i.e., synaptically induced transient pos…
Modulation of information processing by AMPA receptor auxiliary subunits
2020
AMPA-type glutamate receptors (AMPARs) are key molecules of neuronal communication in our brain. The discovery of AMPAR auxiliary subunits, such as proteins of the TARP, CKAMP and CNIH families, fundamentally changed our understanding of how AMPAR function is regulated. Auxiliary subunits control almost all aspects of AMPAR function in the brain. They influence AMPAR assembly, composition, structure, trafficking, subcellular localization and gating. This influence has important implications for synapse function. In the present review, we first discuss how auxiliary subunits affect the strength of synapses by modulating number and localization of AMPARs in synapses as well as their glutamate…
PTEN recruitment controls synaptic and cognitive function in Alzheimer's models
2016
Dyshomeostasis of amyloid-β peptide (Aβ) is responsible for synaptic malfunctions leading to cognitive deficits ranging from mild impairment to full-blown dementia in Alzheimer's disease. Aβ appears to skew synaptic plasticity events toward depression. We found that inhibition of PTEN, a lipid phosphatase that is essential to long-term depression, rescued normal synaptic function and cognition in cellular and animal models of Alzheimer's disease. Conversely, transgenic mice that overexpressed PTEN displayed synaptic depression that mimicked and occluded Aβ-induced depression. Mechanistically, Aβ triggers a PDZ-dependent recruitment of PTEN into the postsynaptic compartment. Using a PTEN kno…
Structure and Synaptic Function of Metal Binding to the Amyloid Precursor Protein and its Proteolytic Fragments
2017
Alzheimer’s disease (AD) is ultimately linked to the Amyloid Precursor Protein (APP). However, current research reveals an important synaptic function of APP and APP-like proteins (APLP1 and 2). In this context various neurotrophic and neuroprotective functions have been reported for the APP proteolytic fragments sAPPα, sAPPβ, and the monomeric amyloid-beta peptide (Aβ). APP is a metalloprotein and binds copper and zinc ions. Synaptic activity correlates with a release of these ions into the synaptic cleft and dysregulation of their homeostasis is linked to different neurodegenerative diseases. Metal binding to APP or its fragments affects its structure and its proteolytic cleavage and ther…
Neurons in the pigeon caudolateral nidopallium differentiate Pavlovian conditioned stimuli but not their associated reward value in a sign-tracking p…
2016
AbstractAnimals exploit visual information to identify objects, form stimulus-reward associations, and prepare appropriate behavioral responses. The nidopallium caudolaterale (NCL), an associative region of the avian endbrain, contains neurons exhibiting prominent response modulation during presentation of reward-predicting visual stimuli, but it is unclear whether neural activity represents valuation signals, stimulus properties, or sensorimotor contingencies. To test the hypothesis that NCL neurons represent stimulus value, we subjected pigeons to a Pavlovian sign-tracking paradigm in which visual cues predicted rewards differing in magnitude (large vs. small) and delay to presentation (s…
Selective α-synuclein knockdown in monoamine neurons by intranasal oligonucleotide delivery: potential therapy for parkinson’s disease
2018
Progressive neuronal death in brainstem nuclei and widespread accumulation of α-synuclein are neuropathological hallmarks of Parkinson’s disease (PD). Reduction of α-synuclein levels is therefore a potential therapy for PD. However, because α-synuclein is essential for neuronal development and function, α-synuclein elimination would dramatically impact brain function. We previously developed conjugated small interfering RNA (siRNA) sequences that selectively target serotonin (5-HT) or norepinephrine (NE) neurons after intranasal administration. Here, we used this strategy to conjugate inhibitory oligonucleotides, siRNA and antisense oligonucleotide (ASO), with the triple monoamine reuptake …