Distinct extended amygdala circuits for divergent motivational states

By Joshua H. Jennings, Dennis R. Sparta, A. Stamatakis, Randall L. Ung, K. Pleil, T. Kash, Garret D. Stuber. Nature, 2013

701 citations recorded by the source corpus.

The co-morbidity of anxiety and dysfunctional reward processing in illnesses such as addiction and depression suggests that common neural circuitry contributes to these disparate neuropsychiatric symptoms. The extended amygdala, including the bed nucleus of the stria terminalis (BNST), modulates fear and anxiety, but also projects to the ventral tegmental area (VTA), a region implicated in reward and aversion, thus providing a candidate neural substrate for integrating diverse emotional states. However, the precise functional connectivity between distinct BNST projection neurons and their postsynaptic targets in the VTA, as well as the role of this circuit in controlling motivational states, have not been described. Here we record and manipulate the activity of genetically and neurochemically identified VTA-projecting BNST neurons in freely behaving mice. Collectively, aversive stimuli exposure produced heterogeneous firing patterns in VTA-projecting BNST neurons. By contrast, in vivo optically identified glutamatergic projection neurons displayed a net enhancement of activity to aversive stimuli, whereas the firing rate of identified GABAergic (γ-aminobutyric acid-containing) projection neurons was suppressed. Channelrhodopsin-2-assisted circuit mapping revealed that both BNST glutamatergic and GABAergic projections preferentially innervate postsynaptic non-dopaminergic VTA neurons, thus providing a mechanistic framework for in vivo circuit perturbations. In vivo photostimulation of BNST glutamatergic projections resulted in aversive and anxiogenic behavioural phenotypes. Conversely, activation of BNST GABAergic projections produced rewarding and anxiolytic phenotypes, which were also recapitulated by direct inhibition of VTA GABAergic neurons. These data demonstrate that functionally opposing BNST to VTA circuits regulate rewarding and aversive motivational states, and may serve as a crucial circuit node for bidirectionally normalizing maladaptive behaviours.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Social Psychology

View Paper: https://www.semanticscholar.org/paper/b094f8c7bc24b675130d787985a6c38dc2555363

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Citations in the corpus

Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences (2016, neutral): “…projection anatomy is one of the most important features that might resolve principal cell population types involved in such distinct processes (Jennings et al., 2013; Kim et al., 2013; Lammel et al., 2012; Namburi et al., 2015), but this feature has been difficult to explore in a brain-wide…”
A Framework for Studying Emotions Across Phylogeny (2014, positive): “…example of such an instantiation in mammals is the amygdala, which has long been associated with negative emotions such as fear, but which has increasingly been associated with positive emotions as well (Gallagher and Chiba, 1996; Paton et al., 2006; Tye et al., 2011; Jennings et al., 2013).”
Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data (2018, positive): “Using in vivo electrophysiological recordings, we previ- ously showed that neurons in the bed nucleus of the stria terminalis (BNST) show strong responses to unpredictable footshock stimuli (Jennings et al., 2013).”