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Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking

Nature volume 475, pages 377380 (21 July 2011) | Download Citation


The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence1,2,3,4,5,21,22,23. The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours4,6,7,24,25, but our understanding of the interaction between these two brain regions has been limited by the inability to manipulate neural-circuit elements of this pathway selectively during behaviour. To circumvent this limitation, we used in vivo optogenetic stimulation or inhibition of glutamatergic fibres from the BLA to the NAc, coupled with intracranial pharmacology and ex vivo electrophysiology. Here we show that optical stimulation of the pathway from the BLA to the NAc in mice reinforces behavioural responding to earn additional optical stimulation of these synaptic inputs. Optical stimulation of these glutamatergic fibres required intra-NAc dopamine D1-type receptor signalling, but not D2-type receptor signalling. Brief optical inhibition of fibres from the BLA to the NAc reduced cue-evoked intake of sucrose, demonstrating an important role of this specific pathway in controlling naturally occurring reward-related behaviour. Moreover, although optical stimulation of glutamatergic fibres from the medial prefrontal cortex to the NAc also elicited reliable excitatory synaptic responses, optical self-stimulation behaviour was not observed by activation of this pathway. These data indicate that whereas the BLA is important for processing both positive and negative affect, the glutamatergic pathway from the BLA to the NAc, in conjunction with dopamine signalling in the NAc, promotes motivated behavioural responding. Thus, optogenetic manipulation of anatomically distinct synaptic inputs to the NAc reveals functionally distinct properties of these inputs in controlling reward-seeking behaviours.

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We thank J. Phillips, V. Kharazia, A. Adamantidis and H.-C. Tsai for assistance and advice. We also thank V. Gukassyan and the UNC Neuroscience Center microscopy core facility. This study was supported by funds from NARSAD, ABMRF, The Foundation of Hope, and NIDA (DA029325), by startup funds provided by the Psychiatry Department at UNC Chapel Hill (G.D.S.) and by the State of California through the University of California at San Francisco (A.B.). D.R.S. was supported by F32AA018610.

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  1. Department of Psychiatry and Department of Cell and Molecular Physiology, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA

    • Garret D. Stuber
    • , Dennis R. Sparta
    •  & Alice M. Stamatakis
  2. Ernest Gallo Clinic and Research Center, Department of Neurology, Wheeler Center for the Neurobiology of Drug Addiction, University of California San Francisco, San Francisco, California 94608, USA

    • Garret D. Stuber
    • , Dennis R. Sparta
    • , Wieke A. van Leeuwen
    • , Juanita E. Hardjoprajitno
    • , Saemi Cho
    • , Kay M. Tye
    • , Kimberly A. Kempadoo
    •  & Antonello Bonci
  3. Department of Bioengineering and Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA

    • Kay M. Tye
    • , Feng Zhang
    •  & Karl Deisseroth
  4. Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA

    • Antonello Bonci


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G.D.S. and A.B. designed, discussed and planned all experiments. G.D.S., D.R.S., A.M.S., W.A.v.L., J.E.H., S.C., K.M.T. and K.A.K. performed experiments. G.D.S., D.R.S., A.M.S. and W.A.v.L. analysed data. F.Z. and K.D. provided resources and training to G.D.S. G.D.S. and A.B. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Garret D. Stuber.

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    Supplementary Information

    This file contains Supplementary Methods, an additional reference and Supplementary Figures 1-17 with legends.

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    Supplementary Movie 1

    This movie file shows the optical self-stimulation of BLA-to-NAc fibres.

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