Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking

Abstract

The basolateral amygdala (BLA) plays a crucial role in emotional learning irrespective of valence1–5. While the BLA projection to the nucleus accumbens (NAc) is hypothesized to modulate cue-triggered motivated behaviors4, 6, 7,, 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 behavior. To circumvent this limitation, we used in vivo optogenetic stimulation or inhibition of glutamatergic fibers from the BLA to the NAc, coupled with intracranial pharmacology and ex vivo electrophysiology. We show that optical stimulation of the BLA-to-NAc pathway in mice reinforces behavioral responding to earn additional optical stimulations of these synaptic inputs. Optical stimulation of BLA-to-NAc glutamatergic fibers required intra-NAc dopamine D1-type, but not D2-type, receptor signaling. Brief optical inhibition of BLA-to-NAc fibers reduced cue-evoked intake of sucrose, demonstrating an important role of this specific pathway in controlling naturally occurring reward-related behavior. Moreover, while optical stimulation of medial prefrontal cortex (mPFC) to NAc glutamatergic fibers also elicited reliable excitatory synaptic responses, optical self-stimulation behavior was not observed by activation of this pathway. These data suggest that while the BLA is important for processing both positive and negative affect, the BLA-to-NAc glutamatergic pathway in conjunction with dopamine signaling in the NAc promotes motivated behavioral responding.

Fiber connectivity between the striatum and cortical and subcortical regions is associated with temperaments in Chinese males

“…Human electrophysiological studies showed a dynamic interaction between the striatum and medial frontal cortex underlying reward-guided learning and decision-making (Cohen, 2007;Cohen et al, 2009). The amygdala was reported to facilitate reward-seeking behaviors by the glutamatergic or dopaminergic neurotransmission in the amygdala-striatum pathway (Lintas et al, 2011;Prevost et al, 2011;Stuber et al, 2011). Bilateral amygdala and nucleus accumbens showed significantly greater response to wins than to losses in both adolescents and adults (Ernst et al, 2005).…”

Activating positive memory engrams suppresses depression-like behaviour

“…The NAC has been heavily implicated in stress responses, mood disorders, and processing natural rewards 2,5,[11][12][13][16][17][18][19][20][21] . Moreover, pathophysiological dysfunction of the NAcc in response to various stressors has been implicated in anhedonia and reward conditioning [18][19][20][21] .…”

“…Moreover, pathophysiological dysfunction of the NAcc in response to various stressors has been implicated in anhedonia and reward conditioning [18][19][20][21] . Our within-subject experiments revealed that, in the TST, the behavioral effects of optically reactivating DG cells labeled by a positive experience were blocked in the group of mice that concurrently received the glutamate receptor antagonists NBQX and AP5 in the NAcc, but not in the group that received saline, without altering basal locomotion (Extended Data Fig.…”

“…The BLA is known to have robust glutamatergic inputs to the NAcc 20 , and previous studies have implicated BLA projections to the NAcc in enabling reward-seeking behavior 20 . We therefore investigated whether the hippocampus (DG)-BLA-NAcc functional pathway is crucial for the real-time light-induced rescue of depression-related behavior.…”

“…Our data dovetail with this circuit's proposed role of relaying BLA stimulus-reward associations to a ventral striatal motor-limbic interface. This interface is thought to be capable of coalescing such information with motivational states and finally translating such activity into behaviorally relevant outputs 5,[18][19][20] .…”