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Séminaire - Eisuke KoyaChanges in appetitive associative strength modulate nucleus accumbens, but not orbitofrontal cortex neuronal ensemble excitability

Abstract :

 Cues that predict the availability of food rewards influence motivational states and elicit food-seeking behaviors.
If a cue no longer predicts food availability, animals may adapt accordingly by inhibiting food seeking responses. Sparsely activated sets of neurons, coined neuronal ensembles, have been shown to encode the strength of reward-cue associations. While alterations in intrinsic excitability have been shown to underlie many learning and memory processes, little is known about these properties specifically on cue-activated neuronal ensembles.
We examined the activation patterns of cue-activated orbitofrontal cortex (OFC) and nucleus accumbens (NAc) shell ensembles using wild-type and Fos-GFP mice following appetitive conditioning with sucrose and extinction learning. We also investigated the neuronal excitability of recently activated, GFP+ neurons in these brain areas using whole-cell electrophysiology in brain slices. Exposure to a sucrose cue elicited activation of neurons in both the NAc shell and OFC. In the NAc shell, but not the OFC, these activated GFP+ neurons were more excitable than surrounding GFP– neurons. Following extinction, the number of neurons activated in both areas was reduced and activated ensembles in neither area exhibited altered excitability.
These data suggest that learning-induced alterations in the intrinsic excitability of neuronal ensembles is regulated dynamically across different brain areas. Furthermore, we show that changes in associative strength modulate the excitability profile of activated ensembles in the NAc shell.

Selected publications

-Koya E, Golden SA, Harvey BK, Guez-Barber DH, Berkow A, Simmons DE, Bossert JM, Nair SG, Uejima JL, Marin MT, Mitchell TB, Farquhar D, Ghosh SC, Mattson BJ, 
Hope BT. Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization. Nat Neurosci. 2009 Aug;12(8):1069-73. doi: 10.1038/nn.2364.

-Koya E, Cruz FC, Ator R, Golden SA, Hoffman AF, Lupica CR, Hope BT. Silent synapses in selectively activated nucleus accumbens neurons following cocaine sensitization. Nat Neurosci. 2012 Nov;15(11):1556-62. doi: 10.1038/nn.3232.

Cruz FC, Koya E, Guez-Barber DH, Bossert JM, Lupica CR, Shaham Y, Hope BT. New technologies for examining the role of neuronal ensembles in drug addiction and fear. Nat Rev Neurosci. 2013 Nov;14(11):743-54. doi: 10.1038/nrn3597. Review.

Ziminski J, Hessler S, Margetts-Smith G, Sieburg MC, Crombag HS, Koya, E. Changes in appetitive associative strength modulate nucleus accumbens, but not orbitofrontal cortex neuronal ensemble excitability. Journal of Neuroscience (Acceptance pending revision).

Scientific focus :

I am currently interested in answering these key research questions: 

  1. Are learned associations about rewarding substances (e.g. food, drugs) and their associated environmental-stimuli mediated by neuronal ensembles in motivationally relevant areas such as the prefrontal cortex and nucleus accumbens?
  2.  Do the neurons that mediate these learned associations exhibit unique intrinsic membrane properties and synaptic physiology? Thus, are these neurons part of a unique neuronal circuit?
    In order to answer these questions we use a variety of approaches including c-Fos immunohistochemistry, and selective silencing and recordings of Fos-expressing neuronal ensembles.