Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Amygdala to Nucleus Accumbens Pathway



Nature 475, 377380 (21 July 2011)

Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking

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

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

Department of Bioengineering and Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA

Kay M. Tye, Feng Zhang & Karl Deisseroth

Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA

Antonello Bonci


The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence. The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours, 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.

These results show that selective activation of BLA, but not mPFC, glutamatergic inputs to the NAc promotes motivated behavioural responding. This is consistent with the hypothesized role of BLA inputs in facilitating responding to cues, and of mPFC inputs in suppressing inappropriate actions. Dopamine signalling that is capable of activating D1Rs during optical self-stimulation sessions could arise from the burst-firing of dopaminergic neurons, time-locked to salient stimuli during behavioural responding. Alternatively, glutamate released from BLA terminals may gate the release of dopamine from dopaminergic fibres in the NAc directly, independently of neuronal activity in the ventral tegmental area. Our results show that afferent-specific glutamatergic neurotransmission from the BLA to the NAc is both necessary and sufficient to promote the expression of motivated behavioural responding.

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