Long-term depression of synaptic transmission in the cerebellum: cellular and molecular mechanisms revisited

1998 ◽  
Vol 55 (1) ◽  
pp. 79-91 ◽  
Author(s):  
Carole Levenes ◽  
Hervé Daniel ◽  
Françis Crépel
Keyword(s):  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Long Term Depression

scholarly journals Specific nanoscale synaptic reshuffling and control of short-term plasticity following NMDAR- and P2XR-dependent Long-Term Depression

2019 ◽  
Author(s):  
Benjamin Compans ◽  
Magalie Martineau ◽  
Remco V. Klaassen ◽  
Thomas M. Bartol ◽  
Corey Butler ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Super Resolution ◽  
Long Term Potentiation ◽  
Global Changes ◽  
Short Term ◽  
Long Term Depression ◽  
Term Potentiation ◽  
And Control

Long-Term Potentiation (LTP) and Long-Term Depression (LTD) of excitatory synaptic transmission are considered as cellular basis of learning and memory. These two forms of synaptic plasticity have been mainly attributed to global changes in the number of synaptic AMPA-type glutamate receptor (AMPAR) through a regulation of the diffusion/trapping balance at the PSD, exocytosis and endocytosis. While the precise molecular mechanisms at the base of LTP have been intensively investigated, the ones involved in LTD remains elusive. Here we combined super-resolution imaging technique, electrophysiology and modeling to describe the various modifications of AMPAR nanoscale organization and their effect on synaptic transmission in response to two different LTD protocols, based on the activation of either NMDA receptors or P2X receptors. While both type of LTD are associated with a decrease in synaptic AMPAR clustering, only NMDAR-dependent LTD is associated with a reorganization of PSD-95 at the nanoscale. This change increases the pool of diffusive AMPAR improving synaptic short-term facilitation through a post-synaptic mechanism. These results demonstrate that specific dynamic reorganization of synapses at the nanoscale during specific LTD paradigm allows to improve the responsiveness of depressed synapses.

Postsynaptic mechanisms underlying long-term depression of GABAergic transmission in neurons of the deep cerebellar nuclei

1996 ◽  
Vol 76 (1) ◽  
pp. 59-68 ◽  
Author(s):  
W. Morishita ◽  
B. R. Sastry
Keyword(s):  
Synaptic Transmission ◽  
Gabaa Receptor ◽  
Cell Voltage ◽  
Cerebellar Nuclei ◽  
Neuronal Membrane ◽  
Gamma Aminobutyric Acid ◽  
Deep Cerebellar Nuclei ◽  
Long Term Depression ◽  
In Cells

1. The mechanisms underlying long-term depression (LTD) of gamma-aminobutyric acid-A (GABAA) receptor-mediated synaptic transmission induced by 10-Hz stimulation of the inhibitory afferents were investigated using perforated and whole cell voltage-clamp recordings from neurons of the deep cerebellar nuclei (DCN). 2. LTD of inhibitory postsynaptic currents (IPSCs) was reliably induced when the 10-Hz stimulation was delivered under current-clamp conditions where the postsynaptic neuronal membrane was allowed to depolarize. 3. Currents elicited by local applications of the GABAA receptor agonist, 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol hydrochloride (THIP) were also depressed during LTD. 4. LTD could be induced heterosynaptically and did not require the activation of GABAA receptors during the 10-Hz stimulation. 5. In cells loaded with QX-314 and superfused with media containing 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonovaleric acid (APV), a series of depolarizing pulses (50 mV, 200 ms) induced a sustained depression of the IPSC. However, this was not observed in cells recorded with high bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)-containing pipette solutions or when they were exposed to the L-type Ca2+ channel antagonist, nitrendipine. 6. The 10-Hz-induced LTD was also inhibited by BAPTA and was significantly reduced when DCN cells were loaded with microcystin LR or treated with okadaic acid, both inhibitors of protein phosphatases. 7. These results indicate that increases in postsynaptic [Ca2+] and phosphatase activity can reduce the efficacy of GABAA receptor-mediated synaptic transmission.

scholarly journals GSK3β Modulates Timing-Dependent Long-Term Depression Through Direct Phosphorylation of Kv4.2 Channels

2018 ◽  
Vol 29 (5) ◽  
pp. 1851-1865 ◽  
Author(s):  
Giuseppe Aceto ◽  
Agnese Re ◽  
Andrea Mattera ◽  
Lucia Leone ◽  
Claudia Colussi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Synaptic Strength ◽  
Spike Timing ◽  
Long Term Depression ◽  
Pharmacological Agents ◽  
Type K ◽  
Molecular Determinant ◽  
K Currents

AbstractSpike timing-dependent plasticity (STDP) is a form of activity-dependent remodeling of synaptic strength that underlies memory formation. Despite its key role in dictating learning rules in the brain circuits, the molecular mechanisms mediating STDP are still poorly understood. Here, we show that spike timing-dependent long-term depression (tLTD) and A-type K+ currents are modulated by pharmacological agents affecting the levels of active glycogen-synthase kinase 3 (GSK3) and by GSK3β knockdown in layer 2/3 of the mouse somatosensory cortex. Moreover, the blockade of A-type K+ currents mimics the effects of GSK3 up-regulation on tLTD and occludes further changes in synaptic strength. Pharmacological, immunohistochemical and biochemical experiments revealed that GSK3β influence over tLTD induction is mediated by direct phosphorylation at Ser-616 of the Kv4.2 subunit, a molecular determinant of A-type K+ currents. Collectively, these results identify the functional interaction between GSK3β and Kv4.2 channel as a novel mechanism for tLTD modulation providing exciting insight into the understanding of GSK3β role in synaptic plasticity.

scholarly journals Impairment of cerebellar long-term depression and GABAergic transmission in prion protein deficient mice ectopically expressing PrPLP/Dpl

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yasushi Kishimoto ◽  
Moritoshi Hirono ◽  
Ryuichiro Atarashi ◽  
Suehiro Sakaguchi ◽  
Tohru Yoshioka ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Prion Protein ◽  
Neural Plasticity ◽  
Late Onset ◽  
Eyeblink Conditioning ◽  
Electrophysiological Study ◽  
Synaptic Function ◽  
Long Term Depression ◽  
Underlying Mechanisms

Abstract Prion protein (PrPC) knockout mice, named as the “Ngsk” strain (Ngsk Prnp0/0 mice), show late-onset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl). Our previous study indicated that the mutant mice also exhibited alterations in cerebellum-dependent delay eyeblink conditioning, even at a young age (16 weeks of age) when neurological changes had not occurred. Thus, this electrophysiological study was designed to examine the synaptic function of the cerebellar cortex in juvenile Ngsk Prnp0/0 mice. We showed that Ngsk Prnp0/0 mice exhibited normal paired-pulse facilitation but impaired long-term depression of excitatory synaptic transmission at synapses between parallel fibres and PCs. GABAA-mediated inhibitory postsynaptic currents recorded from PCs were also weakened in Ngsk Prnp0/0 mice. Furthermore, we confirmed that Ngsk Prnp0/0 mice (7–8-week-old) exhibited abnormalities in delay eyeblink conditioning. Our findings suggest that these alterations in both excitatory and inhibitory synaptic transmission to PCs caused deficits in delay eyeblink conditioning of Ngsk Prnp0/0 mice. Therefore, the Ngsk Prnp0/0 mouse model can contribute to study underlying mechanisms for impairments of synaptic transmission and neural plasticity, and cognitive deficits in the central nervous system.

Long-Term Depression of Temporoammonic-CA1 Hippocampal Synaptic Transmission

1999 ◽  
Vol 81 (3) ◽  
pp. 1036-1044 ◽  
Author(s):  
Hannah Dvorak-Carbone ◽  
Erin M. Schuman
Keyword(s):  
Synaptic Transmission ◽  
Calcium Influx ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Nmda Receptor Antagonist ◽  
Long Term Depression ◽  
Field Recordings ◽  
Old Rats ◽  
Inhibitory Components

Long-term depression of temporoammonic-CA1 hippocampal synaptic transmission. The temporoammonic pathway, the direct projection from layer III of the entorhinal cortex to area CA1 of the hippocampus, includes both excitatory and inhibitory components that are positioned to be an important source of modulation of the hippocampal output. However, little is known about synaptic plasticity in this pathway. We used field recordings in hippocampal slices prepared from mature (6- to 8-wk old) rats to study long-term depression (LTD) in the temporoammonic pathway. Low-frequency (1 Hz) stimulation (LFS) for 10 min resulted in a depression of the field response that lasted for ≥1 h. This depression was saturable by multiple applications of LFS. LTD induction was unaffected by the blockade of either fast (GABAA) or slow (GABAB) inhibition. Temporoammonic LTD was inhibited by the presence of the N-methyl-d-aspartate (NMDA) receptor antagonist AP5, suggesting a dependence on calcium influx. Full recovery from depression could be induced by high-frequency (100 Hz) stimulation (HFS); in the presence of the GABAA antagonist bicuculline, HFS induced recovery above the original baseline level. Similarly, HFS or θ-burst stimulation (TBS) applied to naive slices caused little potentiation, whereas HFS or TBS applied in the presence of bicuculline resulted in significant potentiation of the temporoammonic response. Our results show that, unlike the Schaffer collateral input to CA1, the temporoammonic input in mature animals is easy to depress but difficult to potentiate.

scholarly journals Long-term depression: a cell biological view

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130138 ◽  
Author(s):  
Morgan Sheng ◽  
Ali Ertürk
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dendritic Spines ◽  
Crucial Role ◽  
Molecular Mechanisms ◽  
Signalling Pathways ◽  
Long Term Depression ◽  
A Cell ◽  
Biological Programme

Recent studies of the molecular mechanisms of long-term depression (LTD) suggest a crucial role for the signalling pathways of apoptosis (programmed cell death) in the weakening and elimination of synapses and dendritic spines. With this backdrop, we suggest that LTD can be considered as the electrophysiological aspect of a larger cell biological programme of synapse involution, which uses localized apoptotic mechanisms to sculpt synapses and circuits without causing cell death.

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