Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission

2011 ◽  
Vol 95 (3) ◽  
pp. 296-304 ◽  
Author(s):  
Ann Van der Jeugd ◽  
Tariq Ahmed ◽  
Sylvie Burnouf ◽  
Karim Belarbi ◽  
Malika Hamdame ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Synaptic Transmission ◽  
Learning And Memory ◽  
Late Phase ◽  
Long Term Depression ◽  
Dependent Learning

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 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.

Novel Form of Long-Term Synaptic Depression in Rat Hippocampus Induced By Activation of α1 Adrenergic Receptors

2004 ◽  
Vol 91 (2) ◽  
pp. 1071-1077 ◽  
Author(s):  
Cary L. Scheiderer ◽  
Lynn E. Dobrunz ◽  
Lori L. McMahon
Keyword(s):  
Synaptic Transmission ◽  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Adrenergic System ◽  
Normal Cognitive Function ◽  
Dependent Learning

Neurons located in the locus coeruleus project to hippocampus and provide noradrenergic innervation necessary for hippocampal-dependent learning and memory. The mechanisms underlying the function of norepinephrine (NE) in memory processing are unknown but likely reside in the ability of NE to modulate the efficacy of glutamate synaptic transmission via activation of G-protein-coupled adrenergic receptors. Here we show that application of NE to rat hippocampal slices in vitro induces a long-term depression (LTD) of synaptic transmission at excitatory CA3–CA1 synapses that persists for ≥40 min after agonist washout. This LTD, which we refer to as NE LTD, is mediated by activation of α1 adrenergic receptors because the α1 agonist methoxamine can induce LTD at the same magnitude as that induced with the nonselective adrenergic agonist NE. Furthermore, NE LTD induced by either NE or methoxamine is blocked with the α1 receptor antagonist, prazosin, but is unaffected by antagonists of α2 and β receptors. This plasticity persists in the presence of the GABAA receptor antagonist bicuculline, indicating that adrenergic modulation of GABAA receptor-mediated transmission does not underlie NE LTD. Induction of NE LTD requires presynaptic activity during agonist application and postsynaptic activation of N-methyl-d-aspartate receptors, fulfilling Hebbian criteria of coincident pre- and postsynaptic activity. The expression of NE LTD is likely to be postsynaptic because paired-pulse facilitation ratios during NE LTD expression are not different from baseline, similar to LTD induced by low-frequency stimulation. Thus we report the identification and characterization of a novel Hebbian form of LTD in hippocampus that is induced after activation of α1 adrenergic receptors. This plasticity may be a mechanism by which the adrenergic system participates in normal cognitive function.

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