Homeostatic circuits selectively gate food cue responses in insular cortex

Livneh, Yoav; Ramesh, Rohan N; Burgess, Christian R; Levandowski, Kirsten M; Madara, Joseph C.; Fenselau, Henning; Goldey, Glenn J; Diaz, Veronica E.; Jikomes, Nick; Resch, Jon M.; Lowell, Bradford B.; Andermann, Mark L.

doi:10.1038/nature22375

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Homeostatic circuits selectively gate food cue responses in insular cortex

Author(s): Yoav Livneh , Rohan N. Ramesh , Christian R. Burgess , Kirsten M. Levandowski , Joseph C. Madara , Henning Fenselau , Glenn J. Goldey , Veronica E. Diaz , Nick Jikomes , Jon M. Resch , Bradford B. Lowell , Mark L. Andermann

Publication date Created: June 14 2017

Publication date (Print): June 14 2017

Journal: Nature

Publisher: Springer Nature

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Abstract

A combination of microprism-based cellular imaging to monitor insular cortex visual cue responses in behaving mice across hunger states with circuit mapping and manipulations reveals a neural basis for state-specific biased processing of motivationally relevant cues.

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Summary Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron-based screening, we developed a family of ultra-sensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies, and mice in vivo. In layer 2/3 pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5 - 40 micrometers long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.

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Michael Krashes, Shuichi Koda, ChianPing Ye … (2011)

Several different neuronal populations are involved in regulating energy homeostasis. Among these, agouti-related protein (AgRP) neurons are thought to promote feeding and weight gain; however, the evidence supporting this view is incomplete. Using designer receptors exclusively activated by designer drugs (DREADD) technology to provide specific and reversible regulation of neuronal activity in mice, we have demonstrated that acute activation of AgRP neurons rapidly and dramatically induces feeding, reduces energy expenditure, and ultimately increases fat stores. All these effects returned to baseline after stimulation was withdrawn. In contrast, inhibiting AgRP neuronal activity in hungry mice reduced food intake. Together, these findings demonstrate that AgRP neuron activity is both necessary and sufficient for feeding. Of interest, activating AgRP neurons potently increased motivation for feeding and also drove intense food-seeking behavior, demonstrating that AgRP neurons engage brain sites controlling multiple levels of feeding behavior. Due to its ease of use and suitability for both acute and chronic regulation, DREADD technology is ideally suited for investigating the neural circuits hypothesized to regulate energy balance.

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The amygdala -- an almond-shaped group of nuclei at the heart of the telencephalon -- has been associated with a range of cognitive functions, including emotion, learning, memory, attention and perception. Most current views of amygdala function emphasize its role in negative emotions, such as fear, and in linking negative emotions with other aspects of cognition, such as learning and memory. However, recent evidence supports a role for the amygdala in processing positive emotions as well as negative ones, including learning about the beneficial biological value of stimuli. Indeed, the amygdala's role in stimulus-reward learning might be just as important as its role in processing negative affect and fear conditioning.