Amygdala circuitry mediating reversible and bidirectional control of anxiety

By K. Tye, R. Prakash, Sung-Yon Kim, Lief Ericsson Fenno, Logan Grosenick, H. Zarabi, K. Thompson, Viviana Gradinaru, Charu Ramakrishnan, Karl Deisseroth. Nature, 2011

1,260 citations recorded by the source corpus.

Anxiety—a sustained state of heightened apprehension in the absence of immediate threat—becomes severely debilitating in disease states. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence) and contribute to the aetiology of major depression and substance abuse. Although it has been proposed that the amygdala, a brain region important for emotional processing, has a role in anxiety, the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA)—achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream CeA—exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin (eNpHR3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLA–CeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.

Subfields: Cellular and Molecular Neuroscience, Endocrine and Autonomic Systems

View Paper: https://www.semanticscholar.org/paper/ffc80185f7540e58c28aead0cf3752801f320eb3

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In Cellular and Molecular Neuroscience

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Citations in the corpus

Approach–Avoidance versus Dominance–Submissiveness: A Multilevel Neural Framework on How Testosterone Promotes Social Status (2013, background): “, 2010), which is the pathway by which the BLA controls the CMA (Tye et al., 2011), is independent from vasopressin (Huber et al.”
Optogenetic Dissection of Entorhinal-Hippocampal Functional Connectivity (2013, methodology): “Finally, to confirm the functional diversity of the entorhinal direct inputs to the hippocampus, we adapted an optogenetic backfiring approach (47) for use in in vivo studies.”
Differential control of learning and anxiety along the dorso-ventral axis of the dentate gyrus (2013, background): “Potential candidates for ventral DG stimulation may be the amygdala (Bienvenu et al., 2012; Kishi et al., 2006; Tye et al., 2011) and PFC (Adhikari et al.”
Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement (2011, positive): “While genetically modified mice have enabled substantial advances in neuroscience and have made possible new approaches for circuit analysis with optogenetics (Tsai et al., 2009; Gradinaru et al., 2009; Lobo et al., 2010; Kravitz et al., 2010; Witten et al., 2010; Tye et al., 2011), a generalizable ”
Neural Circuit Motifs in Valence Processing (2018, positive): “For examples of innate valence, the initial application of optogenetic-mediated projection-specific manipulation identified the BLA-CeA projection as anxiolytic (Tye et al., 2011), specifically biased toward the lateral aspect of the CeA (CeL), which in turn produced feedforward inhibition on neuron”
The ecology of human fear: survival optimization and the nervous system (2015, background): “More recently, exciting research in rodents using optogenetics and electrophysiology has implicated BLA-CeA microcircuits in the control of anxiety (Tye et al., 2011).”