Selective impairment of some forms of synaptic plasticity by oligomeric amyloid-β peptide in the mouse hippocampus: Implication of extrasynaptic NMDA receptors

Myriam Kervern, Arnaud Angeli, Olivier Nicole, Frédéric Léveillé, Bénédicte Parent, Vincent Villette, Alain Buisson, Patrick Dutar
JAD. 2012-09-25; 32(1): 183-196
DOI: 10.3233/JAD-2012-120394

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1. J Alzheimers Dis. 2012;32(1):183-96.

Selective impairment of some forms of synaptic plasticity by oligomeric amyloid-β
peptide in the mouse hippocampus: implication of extrasynaptic NMDA receptors.

Kervern M(1), Angeli A, Nicole O, Léveillé F, Parent B, Villette V, Buisson A,
Dutar P.

Author information:
(1)Centre de Psychiatrie et de Neurosciences, UMR 894, Université Paris
Descartes, Sorbonne Paris Cité, Paris, France.

Alzheimer’s disease is characterized by the loss of memory and synaptic damage.
Evidence is accumulating for a causal role of soluble oligomeric species of
amyloid-β peptide (Aβo) in the impairment of synaptic plasticity and cognition
but the precise mechanisms underlying these effects are still not clear. Synaptic
plasticity such as long-term potentiation is thought to underlie learning and
memory. While the effect of Aβ on long-term potentiation is well documented, a
more general understanding of Aβ action on various aspects of plasticity
involving synaptic and extrasynaptic receptors and the nature of the mechanisms
involved in its effects are lacking. Using a combination of electrophysiological
and biochemical techniques in mouse hippocampal slices, we show here that Aβo
drastically affects synaptic plasticities induced by high stimulation frequencies
through the involvement of extrasynaptic glutamate receptors. Experiments on
hippocampal slices as well as on cultured cortical neurons show that Aβo
potentiates extrasynaptic NMDA receptors-mediated responses. Pharmacological
characterization indicates that GluN2B-containing NMDARs are involved in these
responses. When synaptic and extrasynaptic glutamate receptor-mediated effects
are dissociated using cortical neurons in culture, it appears that Aβo has
differential effects on these two receptors types. We conclude that the pool of
extrasynaptic GluN2B-containing NMDARs is a major target of Aβo in the
hippocampus. During high frequency stimulation, Aβo dramatically impairs
long-term neuronal responses.

DOI: 10.3233/JAD-2012-120394
PMID: 22785392 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus