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NogoA restricts synaptic plasticity in the adult hippocampus on a fast time scale


Delekate, A; Zagrebelsky, M; Kramer, S; Schwab, M E; Korte, M (2011). NogoA restricts synaptic plasticity in the adult hippocampus on a fast time scale. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 108(6):2569-2574.

Abstract

Whereas the role of NogoA in limiting axonal fiber growth and regeneration following an injury of the mammalian central nervous system (CNS) is well known, its physiological functions in the mature uninjured CNS are less well characterized. NogoA is mainly expressed by oligodendrocytes, but also by subpopulations of neurons, in particular in plastic regions of the CNS, e.g., in the hippocampus where it is found at synaptic sites. We analyzed synaptic transmission as well as long-term synaptic plasticity (long-term potentiation, LTP) in the presence of function blocking anti-NogoA or anti-Nogo receptor (NgR) antibodies and in NogoA KO mice. Whereas baseline synaptic transmission, short-term plasticity and long-term depression were not affected by either approach, long-term potentiation was significantly increased following NogoA or NgR1 neutralization. Synaptic potentiation thus seems to be restricted by NogoA. Surprisingly, synaptic weakening was not affected by interfering with NogoA signaling. Mechanistically of interest is the observation that by blockade of the GABA(A) receptors normal synaptic strengthening reoccurred in the absence of NogoA signaling. The present results show a unique role of NogoA expressed in the adult hippocampus in restricting physiological synaptic plasticity on a very fast time scale. NogoA could thus serve as an important negative regulator of functional and structural plasticity in mature neuronal networks.

Abstract

Whereas the role of NogoA in limiting axonal fiber growth and regeneration following an injury of the mammalian central nervous system (CNS) is well known, its physiological functions in the mature uninjured CNS are less well characterized. NogoA is mainly expressed by oligodendrocytes, but also by subpopulations of neurons, in particular in plastic regions of the CNS, e.g., in the hippocampus where it is found at synaptic sites. We analyzed synaptic transmission as well as long-term synaptic plasticity (long-term potentiation, LTP) in the presence of function blocking anti-NogoA or anti-Nogo receptor (NgR) antibodies and in NogoA KO mice. Whereas baseline synaptic transmission, short-term plasticity and long-term depression were not affected by either approach, long-term potentiation was significantly increased following NogoA or NgR1 neutralization. Synaptic potentiation thus seems to be restricted by NogoA. Surprisingly, synaptic weakening was not affected by interfering with NogoA signaling. Mechanistically of interest is the observation that by blockade of the GABA(A) receptors normal synaptic strengthening reoccurred in the absence of NogoA signaling. The present results show a unique role of NogoA expressed in the adult hippocampus in restricting physiological synaptic plasticity on a very fast time scale. NogoA could thus serve as an important negative regulator of functional and structural plasticity in mature neuronal networks.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:23 May 2011 13:21
Last Modified:05 Apr 2016 14:55
Publisher:National Academy of Sciences
ISSN:0027-8424
Additional Information:Copyright: National Academy of Sciences USA
Free access at:Official URL. An embargo period may apply.
Publisher DOI:https://doi.org/10.1073/pnas.1013322108
PubMed ID:21262805

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