STRESS, HORMONES AND PLASTICITY
Department: Physiology - Research axis: Molecular & cellular networks

Research subject

One paramount feature of higher organisms is to learn and adapt to changing environments. It is a matter of survival that requires the brain to convert immediate stimuli into long-lasting changes of neural circuits through alterations of neuronal structure and function. If the memory trace is encoded by structural changes in existing circuits, they might be expected to be present at distant time points after learning, to be specific of circuits activated by learning, and sensitive to behavioral contingencies. Dendritic spines, the postsynaptic entity of excitatory synapses, are putative structural proxies of the memory trace.

A fine balance of dendritic spine synapse formation and elimination mitigates the impact of learning on dendritic spine number. How neurons constantly changing morphology can retain information remains a mystery. Which spines survive, which spines are eliminated may encode the structural basis of learning and memory. We use two-photon imaging of dendritic spines during the acquisition and retention of a simple behavioral task to track the engram and test its sensitivity to (1) extreme changing environment, (2) glucocorticoids, the major stress hormone, and (3) cognitive enhancing drugs.

Circadian learning depends on glucocorticoid rhythms and spine plasticity

Mice learning at glucocorticoid oscillation peak enhance the formation of new postsynaptic dendritic spines through a nontranscriptional mechanism requiring actin remodeling via the LIMK1-cofilin-pathway, and performed better on the rotarod task than mice trained during the circadian glucocorticoid trough. The trough is paramount for the retention of motor memories by enhancing the elimination of dendritic spines present before learning, and for the maintenance of newly formed spines via the transcription of new glucocorticoid-sensitive genes.

Stress uses the prosurvival/ growth pathway to form memories

Glucocorticoid receptor (GR) can use the brain-derived neurotrophic factor (BDNF) receptor as a signaling platform to enhance neuronal differentiation. In particular, glucocorticoids require the TrkB-CaMKII-MAPK-pathway to form memories of contextual fear and inhibitory avoidance. Consistently, cognitive disorders are often associated with abnormal GR and neurotrophin signaling. For example, the disruption of glucocorticoid rhythms alters spine plasticity and predispose to cognitive disabilities.

Glucocorticoid receptor action diverges as a function of BDNF signaling

Current knowledge suggests reciprocal actions of glucocorticoids and BDNF on neuronal growth, survival and behavior that suffer from a lack of mechanistic understanding. We find that BDNF exploits GR as a transcription factor to alter glucocorticoid-regulated transcription through GR phosphorylation, which fosters cofactor recruitment to promote a novel gene expression signature and influence neuronal physiology.

 

img.jeanneteau.200

Team

Team leader

Freddy Jeanneteau
CRCN, CNRS


  IGF Nord 005b

  04 34 35 93 09

 

Staff

Amélie Borie
Doctorant(e), CNRS


  IGF Nord 020a

  04 34 35 92 95

 

Margaux Caperaa
Stagiaire, CNRS


  IGF Nord 020

  04 34 35 92 95

 

Pascal Colson
PU-PH, CHU


 

  04 67 33 59 57

 

Michel Desarmenien
DR2, CNRS


  IGF Nord 020a

  04 34 35 92 94

 

Yann Dromard
IE CDD, Inserm


  IGF Nord 005b

  04 34 35 93 09

 

Gilles Guillon
DR1, CNRS


  IGF Nord 019c

  04 34 35 92 93

 

Laurie Maubernard
BTS, CNRS


  IGF Nord 020a

  04 34 35 92 95

 

Major publications

  • Lambert WM, Xu C, Neubert TA, Chao MV, Garabedian MJ, Jeanneteau F. Mol Cell Biol. 2013; 33(18):3700-14
  • Liston C, Cichon J, Jeanneteau F, Zhengping J, Gan WB. Nature Neuroscience 2013;16(6):698-705
  • Jeanneteau F, Lambert M, Bath KG, Lee FS, Garabedian MJ, Chao MV. PNAS 2012;109(4):1305-10
  • Jeanneteau F, Deinhardt K, Myioshi G, Bennett A, Chao MV. Nature Neuroscience. 2010; 13(11):1373-9
  • Jeanneteau F, Garabedian MJ, Chao MV. PNAS 2008; 105(12):4862-7
 

Events