scholarly journals LTP and memory impairment caused by extracellular Aβ and Tau oligomers is APP-dependent

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Daniela Puzzo ◽  
Roberto Piacentini ◽  
Mauro Fá ◽  
Walter Gulisano ◽  
Domenica D Li Puma ◽  
...  
Keyword(s):  
Associative Memory ◽  
Memory Impairment ◽  
Long Term Potentiation ◽  
Neuronal Uptake ◽  
Common Mechanism ◽  
Tau Oligomers ◽  
Term Potentiation ◽  
Induced Defects ◽  
Oligomeric Forms

The concurrent application of subtoxic doses of soluble oligomeric forms of human amyloid-beta (oAβ) and Tau (oTau) proteins impairs memory and its electrophysiological surrogate long-term potentiation (LTP), effects that may be mediated by intra-neuronal oligomers uptake. Intrigued by these findings, we investigated whether oAβ and oTau share a common mechanism when they impair memory and LTP in mice. We found that as already shown for oAβ, also oTau can bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal uptake of oAβ and oTau requires expression of APP. Finally, the toxic effect of both extracellular oAβ and oTau on memory and LTP is dependent upon APP since APP-KO mice were resistant to oAβ- and oTau-induced defects in spatial/associative memory and LTP. Thus, APP might serve as a common therapeutic target against Alzheimer's Disease (AD) and a host of other neurodegenerative diseases characterized by abnormal levels of Aβ and/or Tau.

scholarly journals Cholecystokinin release triggered by NMDA receptors produces LTP and sound–sound associative memory

2019 ◽  
Vol 116 (13) ◽  
pp. 6397-6406 ◽  
Author(s):  
Xi Chen ◽  
Xiao Li ◽  
Yin Ting Wong ◽  
Xuejiao Zheng ◽  
Haitao Wang ◽  
...  
Keyword(s):  
Associative Learning ◽  
Associative Memory ◽  
High Frequency ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Low Frequency Stimulation ◽  
Term Potentiation ◽  
Frequency Stimulation

Memory is stored in neural networks via changes in synaptic strength mediated in part by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). Here we show that a cholecystokinin (CCK)-B receptor (CCKBR) antagonist blocks high-frequency stimulation-induced neocortical LTP, whereas local infusion of CCK induces LTP. CCK−/−mice lacked neocortical LTP and showed deficits in a cue–cue associative learning paradigm; and administration of CCK rescued associative learning deficits. High-frequency stimulation-induced neocortical LTP was completely blocked by either the NMDAR antagonist or the CCKBR antagonist, while application of either NMDA or CCK induced LTP after low-frequency stimulation. In the presence of CCK, LTP was still induced even after blockade of NMDARs. Local application of NMDA induced the release of CCK in the neocortex. These findings suggest that NMDARs control the release of CCK, which enables neocortical LTP and the formation of cue–cue associative memory.

Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment

2016 ◽  
Vol 41 ◽  
pp. 187-199 ◽  
Author(s):  
Perla Moreno-Castilla ◽  
Luis F. Rodriguez-Duran ◽  
Kioko Guzman-Ramos ◽  
Alejandro Barcenas-Femat ◽  
Martha L. Escobar ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Long Term Depression ◽  
Dopaminergic Neurotransmission ◽  
Term Potentiation

scholarly journals Spermidine protects from age-related synaptic alterations at hippocampal mossy fiber-CA3 synapses

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Marta Maglione ◽  
Gaga Kochlamazashvili ◽  
Tobias Eisenberg ◽  
Bence Rácz ◽  
Eva Michael ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Memory Impairment ◽  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Age Related ◽  
Term Potentiation ◽  
Hippocampal Synapses ◽  
Age Dependent ◽  
Age Related Changes

AbstractAging is associated with functional alterations of synapses thought to contribute to age-dependent memory impairment (AMI). While therapeutic avenues to protect from AMI are largely elusive, supplementation of spermidine, a polyamine normally declining with age, has been shown to restore defective proteostasis and to protect from AMI in Drosophila. Here we demonstrate that dietary spermidine protects from age-related synaptic alterations at hippocampal mossy fiber (MF)-CA3 synapses and prevents the aging-induced loss of neuronal mitochondria. Dietary spermidine rescued age-dependent decreases in synaptic vesicle density and largely restored defective presynaptic MF-CA3 long-term potentiation (LTP) at MF-CA3 synapses (MF-CA3) in aged animals. In contrast, spermidine failed to protect CA3-CA1 hippocampal synapses characterized by postsynaptic LTP from age-related changes in function and morphology. Our data demonstrate that dietary spermidine attenuates age-associated deterioration of MF-CA3 synaptic transmission and plasticity. These findings provide a physiological and molecular basis for the future therapeutic usage of spermidine.

A novel cholinergic induction of long-term potentiation in rat hippocampus

1994 ◽  
Vol 72 (4) ◽  
pp. 2034-2040 ◽  
Author(s):  
J. M. Auerbach ◽  
M. Segal
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Extracellular Recording ◽  
Long Term Potentiation ◽  
Common Mechanism ◽  
Excitatory Postsynaptic Potential ◽  
Tetanic Stimulation ◽  
Term Potentiation ◽  
Bath Application

1. We studied long-term cholinergic effects on synaptic transmission in submerged hippocampal slices using intra- and extracellular recording techniques. 2. Bath application of submicromolar concentrations of carbachol (CCh) produced a gradually developing, long-lasting increase in the CA1 excitatory postsynaptic potential and population spike. This potentiation was blocked by atropine and, hence, named muscarinic long-term potentiation (LTPm). Application of DL-2-amino-5-phosphonovaleric acid had no effect on LTPm, indicating that this phenomenon is N-methyl-D-aspartate receptor independent. 3. These effects of CCh were not likely to be due to the blockade of one of several K+ conductances by the drug; the time and concentration dependence of LTPm were different from those associated with cholinergic blockade of K+ conductances. 4. Removal of extracellular calcium (Cao2+) from the bath blocked synaptic transmission. CCh added in calcium-free medium induced LTPm, which was revealed upon removal of the drug by washing with normal calcium-containing medium. Neither cutting CA1-CA3 connections nor cessation of synaptic stimulation interfered with LTPm induction. 5. Application of thapsigargin or H-7 together with CCh blocked LTPm, suggesting the involvement of intracellular calcium (Cai2+) stores and protein kinases, respectively, in the LTPm mechanism. 6. Subthreshold cholinergic stimulation coupled with subthreshold tetanic stimulation caused LTP. CCh had no effect when administered after the LTP mechanism had been saturated by repeated suprathreshold tetani. Tetanic stimulation failed to cause LTP when applied after LTPm had been induced by CCh. These experiments indicate that tetanus-induced potentiation and LTPm share a common mechanism and provide a direct link between ACh and mechanisms of synaptic plasticity.

LEARNING IN AN OSCILLATORY CORTICAL MODEL

Fractals ◽  
2003 ◽  
Vol 11 (supp01) ◽  
pp. 291-300
Author(s):  
SILVIA SCARPETTA ◽  
ZHAOPING LI ◽  
JOHN HERTZ
Keyword(s):  
Associative Memory ◽  
Hebbian Learning ◽  
Learning Rule ◽  
Long Term Potentiation ◽  
Activation Function ◽  
Cortical Model ◽  
Memory State ◽  
Term Potentiation ◽  
Conventional Models

We study a model of generalized-Hebbian learning in asymmetric oscillatory neural networks modeling cortical areas such as hippocampus and olfactory cortex. The learning rule is based on the synaptic plasticity observed experimentally, in particular long-term potentiation and long-term depression of the synaptic efficacies depending on the relative timing of the pre- and postsynaptic activities during learning. The learned memory or representational states can be encoded by both the amplitude and the phase patterns of the oscillating neural populations, enabling more efficient and robust information coding than in conventional models of associative memory or input representation. Depending on the class of nonlinearity of the activation function, the model can function as an associative memory for oscillatory patterns (nonlinearity of class II) or can generalize from or interpolate between the learned states, appropriate for the function of input representation (nonlinearity of class I). In the former case, simulations of the model exhibits a first order transition between the "disordered state" and the "ordered" memory state.

Sulforaphane enhances long-term potentiation and ameliorate scopolamine-induced memory impairment

2021 ◽  
pp. 113467
Author(s):  
Ho-Sub Park ◽  
Eun-Sang Hwang ◽  
Ga-Young Choi ◽  
Hyun-Bum Kim ◽  
Kyun-Seob Park ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Long Term Potentiation ◽  
Term Potentiation

scholarly journals Restoring the pattern of proteoglycan sulphation in perineuronal nets corrects age-related memory loss

2020 ◽  
Author(s):  
Sujeong Yang ◽  
Sylvain Gigout ◽  
Angelo Molinaro ◽  
Yuko Naito-Matsui ◽  
Sam Hilton ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Memory Loss ◽  
Long Term Potentiation ◽  
Perineuronal Nets ◽  
Transgenic Expression ◽  
Aged Mice ◽  
Age Related ◽  
Term Potentiation ◽  
Early Memory

AbstractMemory loss is a usual consequence of ageing and aged mice show progressive deficits in memory tasks. In aged brains, perineuronal nets (PNNs), which are implicated in plasticity and memory, become inhibitory due to decreased 6-sulphation of their glycan chains (C6S). Removal of PNNs or digestion of their glycosaminoglycans rescued age-related memory loss. Premature reduction of permissive C6S by transgenic deletion of chondroitin 6-sulfotransferase led to very early memory loss. However, restoring C6S levels in aged animals by AAV delivery or transgenic expression of 6-sulfotransferase restored memory. Low C6S levels caused loss of cortical long-term potentiation, which was restored by AAV-mediated 6-sulfotransferase delivery. The study shows that loss of C6S in the aged brain leads to declining memory and cognition. Age-related memory impairment was restored by C6S replacement or other interventions targeting perineuronal nets

Sign in / Sign up

Export Citation Format

Share Document