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PMID: 22179109 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Heterogeneous reallocation of presynaptic efficacy in recurrent excitatory circuits adapting to inactivity.

Nature neuroscience ·Vol. 15 ·No. 2 ·2011-12-18 ·Pages 250-7

Mitra A, Mitra SS, Tsien RW

Abstract

Recurrent excitatory circuits face extreme challenges in balancing efficacy and stability. We recorded from CA3 pyramidal neuron pairs in rat hippocampal slice cultures to characterize synaptic and circuit-level changes in recurrent synapses resulting from long-term inactivity. Chronic tetrodotoxin treatment greatly reduced the percentage of connected CA3-CA3 neurons, but enhanced the strength of the remaining connections; presynaptic release probability sharply increased, whereas quantal size was unaltered. Connectivity was decreased in activity-deprived circuits by functional silencing of synapses, whereas three-dimensional anatomical analysis revealed no change in spine or bouton density or aggregate dendrite length. The silencing arose from enhanced Cdk5 activity and could be reverted by acute Cdk5 inhibition with roscovitine. Our results suggest that recurrent circuits adapt to chronic inactivity by reallocating presynaptic weights heterogeneously, strengthening certain connections while silencing others. This restricts synaptic output and input, preserving signaling efficacy among a subset of neuronal ensembles while protecting network stability.

MeSH Terms
Adaptation, Physiological/physiology Anesthetics, Local/pharmacology Animals Animals, Newborn Biophysical Phenomena Colforsin/pharmacology Cyclin-Dependent Kinase 5/metabolism Electric Stimulation Excitatory Postsynaptic Potentials/drug effects,physiology Feedback, Physiological Gene Expression Regulation/drug effects Hippocampus/cytology Nerve Fibers/physiology Nerve Net/drug effects,physiology Nerve Tissue Proteins/metabolism Neurons/cytology Organ Culture Techniques Patch-Clamp Techniques Presynaptic Terminals/drug effects,physiology Protein Kinase Inhibitors/pharmacology Purines/pharmacology Rats Rats, Sprague-Dawley Roscovitine Synapses/drug effects,physiology Tetrodotoxin/pharmacology
Chemicals
Anesthetics, Local Nerve Tissue Proteins Protein Kinase Inhibitors Purines neuronal Cdk5 activator (p25-p35) Roscovitine Colforsin Tetrodotoxin Cyclin-Dependent Kinase 5
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Mitra Ananya
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California, USA.
Mitra Siddhartha S
Tsien Richard W
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Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1546-1726
DOI
10.1038/nn.3004
Published
2011-12-18
Epub
2011-00-18
Pages
250-7
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC3558750
Subset
IM
Grants
NIMH NIH HHS · R37 MH071739-08 · United States
NIMH NIH HHS · R37 MH071739-07 · United States
NIMH NIH HHS · 5R37MH071739 · United States
NIMH NIH HHS · R37 MH071739-09 · United States
NIMH NIH HHS · R37 MH071739 · United States
External Links
PubMed source DOI: 10.1038/nn.3004 PMC Full Text View journal details
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