scholarly journals Developmental Time Course of SNAP-25 Isoforms Regulate Hippocampal Long-Term Synaptic Plasticity and Hippocampus-Dependent Learning

2020 ◽  
Vol 21 (4) ◽  
pp. 1448
Author(s):  
Katisha R. Gopaul ◽  
Muhammad Irfan ◽  
Omid Miry ◽  
Linnea R. Vose ◽  
Alexander Moghadam ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Time Course ◽  
Splice Variants ◽  
Developmental Regulation ◽  
Release Kinetics ◽  
Long Term Potentiation ◽  
Developmental Time ◽  
Compensatory Mechanisms ◽  
Schaffer Collateral

SNAP-25 is essential to activity-dependent vesicle fusion and neurotransmitter release in the nervous system. During early development and adulthood, SNAP-25 appears to have differential influences on short- and long-term synaptic plasticity. The involvement of SNAP-25 in these processes may be different at hippocampal and neocortical synapses because of the presence of two different splice variants, which are developmentally regulated. We show here that the isoform SNAP-25a, which is expressed first developmentally in rodent brain, contributes to developmental regulation of the expression of both long-term depression (LTD) and long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in the hippocampus. In one month old mice lacking the developmentally later expressed isoform SNAP-25b, Schaffer collateral-CA1 synapses showed faster release kinetics, decreased LTP and enhanced LTD. By four months of age, SNAP-25b-deficient mice appeared to have compensated for the lack of the adult SNAP-25b isoform, now exhibiting larger LTP and no differences in LTD compared to wild type mice. Interestingly, learning a hippocampus-dependent task reversed the reductions in LTP, but not LTD, seen at one month of age. In four month old adult mice, learning prevented the compensatory up-regulation of LTD that we observed prior to training. These findings support the hypothesis that SNAP-25b promotes stronger LTP and weakens LTD at Schaffer collateral-CA1 synapses in young mice, and suggest that compensatory mechanisms can reverse alterations in synaptic plasticity associated with a lack of SNAP-25b, once mice reach adulthood.

scholarly journals Developmental time course of SNAP-25 isoform regulation of hippocampal long-term synaptic plasticity and hippocampus-dependent learning

2019 ◽  
Author(s):  
Katisha R. Gopaul ◽  
Muhammad Irfan ◽  
Omid Miry ◽  
Linnea R. Vose ◽  
Alexander A. Moghadam ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Neurons ◽  
Time Course ◽  
Splice Variants ◽  
Developmental Regulation ◽  
Release Kinetics ◽  
Developmental Time ◽  
Compensatory Mechanisms ◽  
Schaffer Collateral ◽  
Dependent Learning

SNAP-25 is essential in activity-dependent vesicle fusion and neurotransmitter release in the nervous system. During development and adulthood, SNAP-25 appears to have differential influences on long- and short-term synaptic plasticity in the hippocampus. The involvement of SNAP-25 in this process may be altered by two different splice variants expressed in adolescences versus adulthood in hippocampal neurons. This study suggests that the adolescent isoform, SNAP-25a can contribute to developmental regulation of the expression of LTD and LTP. In mice deficient in SNAP-25b, the adult isoform, Schaffer collateral-CA1 synapses showed slower release kinetics, reduced initial release probabilities, decreased LTP and enhanced LTD at 1 month. By 4 months of age, when mice have fully developed in the absence of SNAP-25b, the gene targeted mice appear to have compensated for the lack of the adult SNAP-25b isoform. Moreover, hippocampal-dependent training reversed reductions in LTP, but not LTD, seen at 1 month. In 4 month old adult mice, training prevented the compensatory reversal of LTD that had been observed prior to training. These findings support the hypothesis that immature SNAP-25a plays a strong role in the expression of plasticity at Schaffer collateral-CA1 synapses in adolescent mice, but compensatory mechanisms that reverse alterations in synaptic plasticity once mice reach adulthood.

scholarly journals Developmental regulation of the late phase of long-term potentiation (L-LTP) and metaplasticity in hippocampal area CA1 of the rat

2012 ◽  
Vol 107 (3) ◽  
pp. 902-912 ◽  
Author(s):  
Guan Cao ◽  
Kristen M. Harris
Keyword(s):  
Synaptic Plasticity ◽  
Developmental Regulation ◽  
Late Phase ◽  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Developmentally Regulated ◽  
Area Ca1 ◽  
Term Potentiation ◽  
Hippocampal Area

Long-term potentiation (LTP) is a form of synaptic plasticity thought to underlie memory; thus knowing its developmental profile is fundamental to understanding function. Like memory, LTP has multiple phases with distinct timing and mechanisms. The late phase of LTP (L-LTP), lasting longer than 3 h, is protein synthesis dependent and involves changes in the structure and content of dendritic spines, the major sites of excitatory synapses. In previous work, tetanic stimulation first produced L-LTP at postnatal day 15 (P15) in area CA1 of rat hippocampus. Here we used a more robust induction paradigm involving theta-burst stimulation (TBS) in acute slices and found the developmental onset of L-LTP to be 3 days earlier at P12. In contrast, at P8–11, TBS only reversed the synaptic depression that occurs from test-pulse stimulation in developing (P8–15) hippocampus. A second bout of TBS delivered 30–180 min later produced L-LTP at P10–11 but not at P8–9 and enhanced L-LTP at P12–15. Both the developmental onset and the enhanced L-LTP produced by repeated bouts of TBS were blocked by the N-methyl-d-aspartate receptor antagonist dl-2-amino-5-phosphonovaleric acid. Thus the developmental onset age is P12 for L-LTP induced by the more robust and perhaps more naturalistic TBS induction paradigm. Metaplasticity produced by repeated bouts of TBS is developmentally regulated, advancing the capacity for L-LTP from P12 to P10, but not to younger ages. Together these findings provide a new basis from which to investigate mechanisms that regulate the developmental onset of this important form of synaptic plasticity.

scholarly journals Calcium-permeable AMPA receptors mediate timing-dependent LTP elicited by 6 coincident action potentials at Schaffer collateral-CA1 synapses

2019 ◽  
Author(s):  
Efrain A. Cepeda-Prado ◽  
Babak Khodaie ◽  
Gloria D. Quiceno ◽  
Swantje Beythien ◽  
Volkmar Leßmann ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Action Potential ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Spike Timing ◽  
High Frequency Stimulation ◽  
Single Trial ◽  
Schaffer Collateral ◽  
Frequency Stimulation

AbstractActivity-dependent synaptic plasticity in neuronal circuits represents a cellular model of memory formation. Such changes can be elicited by repeated high-frequency stimulation inducing long-term potentiation (LTP), or by low frequency stimulation induced long-term depression (LTD). Spike timing-dependent plasticity (STDP) can induce equally robust long-lasting timing-dependent LTP (t-LTP) in response to low frequency repeats of coincident action potential (AP) firing in presynaptic cells followed by postsynaptic neurons. Conversely, this stimulation can lead to t-LTD if the postsynaptic spike precedes the presynaptic action potential. STDP is best suited to investigate synaptic plasticity mechanisms at the single cell level. Commonly, STDP paradigms relying on 25-100 repeats of coincident pre- and postsynaptic firing are used to elicit t-LTP or t-LTD. However, the minimum number of repeats required for successful STDP induction, which could account for fast single trial learning in vivo, is barely explored. Here, we examined low repeat STDP at Schaffer collateral-CA1 synapses by pairing one presynaptic AP with either one postsynaptic AP (1:1 t-LTP) or a burst of 4 APs (1:4 t-LTP). We found 3-6 repeats to be sufficient to elicit t-LTP. Postsynaptic Ca2+ elevation for 1:1 t-LTP required NMDARs and L-type VGCCs, while 1:4 t-LTP depended on metabotropic GluR and ryanodine receptor signaling. Surprisingly, both 6x t-LTP variants were strictly dependent on activation of postsynaptic Ca2+-permeable AMPARs. Both t-LTP forms were regulated differentially by dopamine receptors, but occurred independent from BDNF/TrkB signaling. Our data show that synaptic changes induced by only 3-6 repeats of mild STDP stimulation occuring in ≤10 s can take place on time scales observed also during single trial learning.

Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Yu-Xing Ge ◽  
Ying-Ying Lin ◽  
Qian-Qian Bi ◽  
Yu-Juan Chen
Keyword(s):  
Synaptic Plasticity ◽  
Temporal Lobe Epilepsy ◽  
Synaptic Vesicle ◽  
Long Term Potentiation ◽  
Synaptic Dysfunction ◽  
Over Expression ◽  
Term Potentiation ◽  
Synaptic Vesicle Protein 2A

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

Prenatal stress in rats attenuates hippocampal long-term potentiation and induces deficits in synaptic plasticity

2006 ◽  
Vol 16 ◽  
pp. S52
Author(s):  
S. Salomon ◽  
Y. Nachum-Biala ◽  
Y. Bogush ◽  
M. Lineal ◽  
H. Matzner ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Prenatal Stress ◽  
Long Term Potentiation ◽  
Term Potentiation

scholarly journals Protein kinase D promotes plasticity-induced F-actin stabilization in dendritic spines and regulates memory formation

2015 ◽  
Vol 210 (5) ◽  
pp. 771-783 ◽  
Author(s):  
Norbert Bencsik ◽  
Zsófia Szíber ◽  
Hanna Liliom ◽  
Krisztián Tárnok ◽  
Sándor Borbély ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Protein Kinase ◽  
Dendritic Spines ◽  
Morphological Changes ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Protein Kinase D

Actin turnover in dendritic spines influences spine development, morphology, and plasticity, with functional consequences on learning and memory formation. In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways. Using in vitro models of neuronal plasticity, such as glycine-induced chemical long-term potentiation (LTP), known to evoke synaptic plasticity, or long-term depolarization block by KCl, leading to homeostatic morphological changes, we show that actin stabilization needed for the enlargement of dendritic spines is dependent on PKD activity. Consequently, impaired PKD functions attenuate activity-dependent changes in hippocampal dendritic spines, including LTP formation, cause morphological alterations in vivo, and have deleterious consequences on spatial memory formation. We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulating actin stability in dendritic spines.

scholarly journals Synaptic plasticity-dependent competition rule influences memory formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yire Jeong ◽  
Hye-Yeon Cho ◽  
Mujun Kim ◽  
Jung-Pyo Oh ◽  
Min Soo Kang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Fear Conditioning ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Specific Pattern ◽  
Memory Encoding ◽  
Competition Rule ◽  
Term Potentiation ◽  
Input Activity

AbstractMemory is supported by a specific collection of neurons distributed in broad brain areas, an engram. Despite recent advances in identifying an engram, how the engram is created during memory formation remains elusive. To explore the relation between a specific pattern of input activity and memory allocation, here we target a sparse subset of neurons in the auditory cortex and thalamus. The synaptic inputs from these neurons to the lateral amygdala (LA) are not potentiated by fear conditioning. Using an optogenetic priming stimulus, we manipulate these synapses to be potentiated by the learning. In this condition, fear memory is preferentially encoded in the manipulated cell ensembles. This change, however, is abolished with optical long-term depression (LTD) delivered shortly after training. Conversely, delivering optical long-term potentiation (LTP) alone shortly after fear conditioning is sufficient to induce the preferential memory encoding. These results suggest a synaptic plasticity-dependent competition rule underlying memory formation.

Noradrenergic Regulation of Synaptic Plasticity in the Hippocampal CA1 Region

1997 ◽  
Vol 77 (6) ◽  
pp. 3013-3020 ◽  
Author(s):  
Hiroshi Katsuki ◽  
Yukitoshi Izumi ◽  
Charles F. Zorumski
Keyword(s):  
Synaptic Plasticity ◽  
Receptor Antagonist ◽  
Hippocampal Slices ◽  
Stimulus Frequency ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

Katsuki, Hiroshi, Yukitoshi Izumi, and Charles F. Zorumski. Noradrenergic regulation of synaptic plasticity in the hippocampal CA1 region. J. Neurophysiol. 77: 3013–3020, 1997. The effects of norepinephrine (NE) and related agents on long-lasting changes in synaptic efficacy induced by several patterns of afferent stimuli were investigated in the CA1 region of rat hippocampal slices. NE (10 μM) showed little effect on the induction of long-term potentiation (LTP) triggered by theta-burst-patterned stimulation, whereas it inhibited the induction of long-term depression (LTD) triggered by 900 pulses of 1-Hz stimulation. In nontreated slices, 900 pulses of stimuli induced LTD when applied at lower frequencies (1–3 Hz), and induced LTP when applied at a higher frequency (30 Hz). NE (10 μM) caused a shift of the frequency-response relationship in the direction preferring potentiation. The effect of NE was most prominent at a stimulus frequency of 10 Hz, which induced no changes in control slices but clearly induced LTP in the presence of NE. The facilitating effect of NE on the induction of LTP by 10-Hz stimulation was blocked by theβ-adrenergic receptor antagonist timolol (50 μM), but not by the α receptor antagonist phentolamine (50 μM), and was mimicked by the β-agonist isoproterenol (0.3 μM), but not by the α1 agonist phenylephrine (10 μM). The induction of LTD by 1-Hz stimulation was prevented by isoproterenol but not by phenylephrine, indicating that the activation of β-receptors is responsible for these effects of NE. NE (10 μM) also prevented the reversal of LTP (depotentiation) by 900 pulses of 1-Hz stimulation delivered 30 min after LTP induction. In contrast to effects on naive (nonpotentiated) synapses, the effect of NE on previously potentiated synapses was only partially mimicked by isoproterenol, but fully mimicked by coapplication of phenylephrine and isoproterenol. In addition, the effect of NE was attenuated either by phentolamine or by timolol, indicating that activation of both α1 and β-receptors is required. These results show that NE plays a modulatory role in the induction of hippocampal synaptic plasticity. Althoughβ-receptor activation is essential, α1 receptor activation is also necessary in determining effects on previously potentiated synapses.

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