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Pflugers Archiv : European Journal of... Aug 2018In a previous study, we pointed out that the neurotoxic action evoked by methylmercury (MeHg), a potent environmental pollutant responsible for fatal food poisoning, is...
In a previous study, we pointed out that the neurotoxic action evoked by methylmercury (MeHg), a potent environmental pollutant responsible for fatal food poisoning, is associated with alterations of cellular excitability by irreversible blockade of sodium and calcium currents. Here, we investigated the MeHg effects on synaptic transmission and neuronal plasticity using extracellular field recording in CA1 area of rat hippocampal slices. MeHg caused a fast and drastic depression of evoked field excitatory postsynaptic potentials (fEPSPs) in a concentration-dependent manner with an IC of 25.7 μM. This depression was partially caused by the irreversible reduction of axon recruitment deduced from the decrement of the fiber volley (FV) amplitude. Nevertheless, this MeHg-induced synaptic depression represents a true reduction of synaptic efficacy, as judged by input/output curves. In addition, a reduction on presynaptic release of glutamate was detected with the paradigm of paired-pulse facilitation during MeHg application. Moreover, MeHg also reduced population spike (PS) ampxlitude, and this effect was more prominent when the PS was evoked by ortodromic stimulation than by antidromic stimulation. Interestingly, despite these strong effects of MeHg on synaptic transmission and excitability, this compound did not modify the induction of long-term synaptic potentiation (LTP). The effects described here for MeHg were irreversible or very slowly reversible after drug wash-out. In summary, the blockade of sodium and calcium channels by MeHg affects synaptic transmission and cellular excitability but not synaptic plasticity.
Topics: Animals; Electric Stimulation; Excitatory Postsynaptic Potentials; Hippocampus; Long-Term Potentiation; Male; Methylmercury Compounds; Neuronal Plasticity; Neurons; Rats; Rats, Sprague-Dawley; Synaptic Transmission; Temporal Lobe
PubMed: 29679296
DOI: 10.1007/s00424-018-2144-x -
BioMed Research International 2015Neuroligins (NLs) are postsynaptic transmembrane cell-adhesion proteins that play a key role in the regulation of excitatory and inhibitory synapses. Previous in vitro... (Review)
Review
Neuroligins (NLs) are postsynaptic transmembrane cell-adhesion proteins that play a key role in the regulation of excitatory and inhibitory synapses. Previous in vitro and in vivo studies have suggested that NLs contribute to synapse formation and synaptic transmission. Consistent with their localization, NL1 and NL3 selectively affect excitatory synapses, whereas NL2 specifically affects inhibitory synapses. Deletions or mutations in NL genes have been found in patients with autism spectrum disorders or mental retardations, and mice harboring the reported NL deletions or mutations exhibit autism-related behaviors and synapse dysfunction. Conversely, synaptic activity can regulate the phosphorylation, expression, and cleavage of NLs, which, in turn, can influence synaptic activity. Thus, in clinical research, identifying the relationship between NLs and synapse function is critical. In this review, we primarily discuss how NLs and synaptic activity influence each other.
Topics: Animals; Central Nervous System; Humans; Membrane Proteins; Nerve Tissue Proteins; Synapses; Synaptic Transmission
PubMed: 25839034
DOI: 10.1155/2015/498957 -
Current Opinion in Neurobiology Dec 2015Cell adhesion molecules (CAMs) play a crucial role in organizing the synaptic interface and regulating synapse activity. In turn, CAMs can influence a variety of higher... (Review)
Review
Cell adhesion molecules (CAMs) play a crucial role in organizing the synaptic interface and regulating synapse activity. In turn, CAMs can influence a variety of higher brain functions. In addition to their bona fide interacting partners on the apposed cell surface or the extracellular matrix (ECM) with which they form molecular bridges, synaptic CAMs bind to many other proteins with their intracellular and extracellular domains. The resulting multi-molecular complexes at the active zone and at the postsynaptic density (PSD) are thought to anchor components requisite for synaptic transmission. Recent studies demonstrating the proteolytic cleavage of synaptic CAMs underscore an exciting mechanism through which the synaptic microenvironment can be altered and thereby finely tune the efficacy of synaptic transmission.
Topics: Animals; Cell Adhesion Molecules; Humans; Proteolysis; Synaptic Transmission
PubMed: 26318535
DOI: 10.1016/j.conb.2015.08.005 -
Neuropharmacology Jul 2021In this review we consider the various roles played by N-methyl-d-aspartate receptors (NMDARs) located on pyramidal neurones in medial prefrontal cortex (mPFC). We focus... (Review)
Review
In this review we consider the various roles played by N-methyl-d-aspartate receptors (NMDARs) located on pyramidal neurones in medial prefrontal cortex (mPFC). We focus on recent data from our lab that has investigated how NMDARs contribute to ongoing synaptic transmission in a frequency dependent manner, the plasticity of NMDARs and how this impacts their contribution to synaptic transmission, and finally consider how NMDARs contribute to plasticity induced by synchronous activation of two separate inputs to mPFC.
Topics: Animals; Humans; Long-Term Potentiation; Neuronal Plasticity; Prefrontal Cortex; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission
PubMed: 34022178
DOI: 10.1016/j.neuropharm.2021.108614 -
Progress in Neurobiology Sep 2022Measurements of the time elapsed during synaptic transmission has shown that synaptic vesicle (SV) fusion lags behind Ca-influx by approximately 60 microseconds (µsec)....
Measurements of the time elapsed during synaptic transmission has shown that synaptic vesicle (SV) fusion lags behind Ca-influx by approximately 60 microseconds (µsec). The conventional model cannot explain this extreme rapidity of the release event. Synaptic transmission occurs at the active zone (AZ), which comprises of two pools of SV, non-releasable "tethered" vesicles, and a readily-releasable pool of channel-associated Ca-primed vesicles, "RRP". A recent TIRF study at cerebellar-mossy fiber-terminal, showed that subsequent to an action potential, newly "tethered" vesicles, became fusion-competent in a Ca-dependent manner, 300-400 ms after tethering, but were not fused. This time resolution may correspond to priming of tethered vesicles through Ca-binding to Syt1/Munc13-1/complexin. It confirms that Ca-priming and Ca-influx-independent fusion, are two distinct events. Notably, we have established that Ca channel signals evoked-release in an ion flux-independent manner, demonstrated by Ca-impermeable channel, or by substitution of Ca with channel -impermeable La. Thus, conformational changes in a channel coupled to RRP appear to directly activate the release machinery and account for a µsec Ca-influx-independent vesicle fusion. Rapid vesicle fusion driven by non-ionotropic channel signaling strengthens a conformational-coupling mechanism of synaptic transmission, and contributes to better understanding of neuronal communication vital for brain function.
Topics: Calcium; Exocytosis; Humans; Neurons; Synaptic Transmission; Synaptic Vesicles
PubMed: 35760141
DOI: 10.1016/j.pneurobio.2022.102312 -
Neuropharmacology Sep 2017Endocannabinoids (eCBs) are a family of lipid molecules that act as key regulators of synaptic transmission and plasticity. They are synthetized "on demand" following... (Review)
Review
Endocannabinoids (eCBs) are a family of lipid molecules that act as key regulators of synaptic transmission and plasticity. They are synthetized "on demand" following physiological and/or pathological stimuli. Once released from postsynaptic neurons, eCBs typically act as retrograde messengers to activate presynaptic type 1 cannabinoid receptors (CB) and induce short- or long-term depression of neurotransmitter release. Besides this canonical mechanism of action, recent findings have revealed a number of less conventional mechanisms by which eCBs regulate neural activity and synaptic function, suggesting that eCB-mediated plasticity is mechanistically more diverse than anticipated. These mechanisms include non-retrograde signaling, signaling via astrocytes, participation in long-term potentiation, and the involvement of mitochondrial CB. Focusing on paradigmatic brain areas, such as hippocampus, striatum, and neocortex, we review typical and novel signaling mechanisms, and discuss the functional implications in normal brain function and brain diseases. In summary, eCB signaling may lead to different forms of synaptic plasticity through activation of a plethora of mechanisms, which provide further complexity to the functional consequences of eCB signaling. This article is part of the Special Issue entitled "A New Dawn in Cannabinoid Neurobiology".
Topics: Animals; Brain; Brain Diseases; Endocannabinoids; Humans; Neuronal Plasticity; Synaptic Transmission
PubMed: 28625718
DOI: 10.1016/j.neuropharm.2017.06.017 -
International Journal of Molecular... Feb 2021Distinct from ovarian estradiol, the steroid hormone 17ß-estradiol (E2) is produced in the brain and is involved in numerous functions, particularly acting as a... (Comparative Study)
Comparative Study
Distinct from ovarian estradiol, the steroid hormone 17ß-estradiol (E2) is produced in the brain and is involved in numerous functions, particularly acting as a neurosteroid. However, the physiological role of E2 and the mechanism of its effects are not well known. In hippocampal slices, 17ß-estradiol has been found to cause a modest increase in fast glutamatergic transmission; because some of these effects are rapid and acute, they might be mediated by membrane-associated receptors via nongenomic action. Moreover, activation of membrane estrogen receptors can rapidly modulate neuron function in a sex-specific manner. To further investigate the neurological role of E2, we examined the effect of E2, as an estrogen receptor (ER) agonist, on synaptic transmission in slices of the prefrontal cortex (PFC) and hippocampus in both male and female mice. Whole-cell recordings of spontaneous excitatory postsynaptic currents (sEPSC) in the PFC showed that E2 acts as a neuromodulator in glutamatergic transmission in the PFC in both sexes, but often in a cell-specific manner. The sEPSC amplitude and/or frequency responded to E2 in three ways, namely by significantly increasing, decreasing or having no response. Additional experiments using an agonist selective for ERß, diarylpropionitrile (DPN) showed that in males the sEPSC and spontaneous inhibitory postsynaptic currents sIPSC responses were similar to their E2 responses, but in females the estrogen receptor ß (ERß) agonist DPN did not influence excitatory transmission in the PFC. In contrast, in the hippocampus of both sexes E2 potentiated the gluatmatergic synaptic transmission in a subset of hippocampal cells. These data indicate that activation of E2 targeting probably a estrogen subtypes or different downstream signaling affect synaptic transmission in the brain PFC and hippocampus between males versus females mice.
Topics: Animals; Estradiol; Estrogen Receptor alpha; Excitatory Amino Acid Agents; Excitatory Postsynaptic Potentials; Female; GABA Agents; Hippocampus; Inhibitory Postsynaptic Potentials; Kinetics; Male; Mice; Mice, Inbred C57BL; Nitriles; Patch-Clamp Techniques; Prefrontal Cortex; Propionates; Sex Characteristics; Synaptic Transmission
PubMed: 33540803
DOI: 10.3390/ijms22031485 -
Nature Neuroscience Nov 2015Synaptic dysfunction is a hallmark of many neurodegenerative and psychiatric brain disorders, yet we know little about the mechanisms that underlie synaptic... (Review)
Review
Synaptic dysfunction is a hallmark of many neurodegenerative and psychiatric brain disorders, yet we know little about the mechanisms that underlie synaptic vulnerability. Although neuroinflammation and reactive gliosis are prominent in virtually every CNS disease, glia are largely viewed as passive responders to neuronal damage rather than drivers of synaptic dysfunction. This perspective is changing with the growing realization that glia actively signal with neurons and influence synaptic development, transmission and plasticity through an array of secreted and contact-dependent signals. We propose that disruptions in neuron-glia signaling contribute to synaptic and cognitive impairment in disease. Illuminating the mechanisms by which glia influence synapse function may lead to the development of new therapies and biomarkers for synaptic dysfunction.
Topics: Animals; Astrocytes; Cognition Disorders; Humans; Neuroglia; Neuronal Plasticity; Neurons; Synaptic Transmission
PubMed: 26505565
DOI: 10.1038/nn.4142 -
Trends in Neurosciences Oct 2014The function of neural circuits depends on the precise connectivity between populations of neurons. Increasing evidence indicates that disruptions in excitatory or... (Review)
Review
The function of neural circuits depends on the precise connectivity between populations of neurons. Increasing evidence indicates that disruptions in excitatory or inhibitory synapse formation or function lead to excitation/inhibition (E/I) imbalances and contribute to neurodevelopmental and psychiatric disorders. Leucine-rich repeat (LRR)-containing surface proteins have emerged as key organizers of excitatory and inhibitory synapses. Distinct LRR proteins are expressed in different cell types and interact with key pre- and postsynaptic proteins. These protein interaction networks allow LRR proteins to coordinate pre- and postsynaptic elements during synapse formation and differentiation, pathway-specific synapse development, and synaptic plasticity. LRR proteins, therefore, play a critical role in organizing synaptic connections into functional neural circuits, and their dysfunction may contribute to neuropsychiatric disorders.
Topics: Animals; Humans; Leucine-Rich Repeat Proteins; Neural Pathways; Proteins; Synapses; Synaptic Transmission
PubMed: 25131359
DOI: 10.1016/j.tins.2014.07.004 -
Philosophical Transactions of the Royal... Oct 2014The influence of astrocytes on synaptic function has been increasingly studied, owing to the discovery of both gliotransmission and morphological ensheathment of... (Review)
Review
The influence of astrocytes on synaptic function has been increasingly studied, owing to the discovery of both gliotransmission and morphological ensheathment of synapses. While astrocytes exhibit at best modest membrane potential fluctuations, activation of G-protein coupled receptors (GPCRs) leads to a prominent elevation of intracellular calcium which has been reported to correlate with gliotransmission. In this review, the possible role of astrocytic GPCR activation is discussed as a trigger to promote synaptic plasticity, by affecting synaptic receptors through gliotransmitters. Moreover, we suggest that volume transmission of neuromodulators could be a biological mechanism to activate astrocytic GPCRs and thereby to switch synaptic networks to the plastic mode during states of attention in cerebral cortical structures.
Topics: Astrocytes; Models, Neurological; Neuronal Plasticity; Neurotransmitter Agents; Receptors, G-Protein-Coupled; Synaptic Transmission
PubMed: 25225097
DOI: 10.1098/rstb.2013.0604