Remote Control of Neuronal Signaling

Rogan, Sarah C.; Roth, Bryan L.

doi:10.1124/pr.110.003020

Cited by 309 publications

(293 citation statements)

References 170 publications

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“…To corroborate these findings, we expressed hM3Dq in Agrp neurons by injecting Agrp-Cre mice with a recombinant AAV vector carrying a credependent coding sequence (rAAV-FLEX-hM3Dq-mCherry). The activation of Agrp neurons by peripheral injection of the receptor ligand, clozapine-N-oxide (CNO, 0.3 mg/kg, i.p), led to similar results as observed in Agrp-Trpv1 mice injected with capsaicin ( Figure S2) but with a delayed response, consistent with the slow effect of hM3Dq in stimulating neuronal activity (Krashes et al, 2011;Rogan and Roth, 2011). Altogether, we conclude that activation of the Agrp neurons resembles many, but not all, aspects of food deprivation.…”

Section: Repertoire Of Home-cage Behaviorssupporting

confidence: 60%

Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding

Dietrich¹,

Zimmer²,

Bober³

et al. 2017

Cell

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SUMMARYThe nervous system evolved to coordinate flexible goal-directed behaviors by integrating interoceptive and sensory information. Hypothalamic Agrp neurons are known to be crucial for feeding behavior. Here, however, we show that these neurons also orchestrate other complex behaviors in adult mice. Activation of Agrp neurons in the absence of food triggers foraging and repetitive behaviors, which are reverted by food consumption. These stereotypic behaviors that are triggered by Agrp neurons are coupled with decreased anxiety. NPY 5 receptor signaling is necessary to mediate the repetitive behaviors after Agrp neuron activation while having minor effects on feeding. Thus, we have unmasked a functional role for Agrp neurons in controlling repetitive behaviors mediated, at least in part, by neuropeptidergic signaling. The findings reveal a new set of behaviors coupled to the energy homeostasis circuit and suggest potential therapeutic avenues for diseases with stereotypic behaviors.

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Section: Repertoire Of Home-cage Behaviorssupporting

confidence: 60%

Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding

Dietrich¹,

Zimmer²,

Bober³

et al. 2017

Cell

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“…We utilized DREADDS. These receptors are highly selective for coupling to Gαs pathways over other G-proteins (Ferguson et al, 2013;Guettier et al, 2009;Rogan and Roth, 2011). Utilizing the rM3Ds Gαs DREADD receptor packaged in a virus under a CAMKIIα promoter (rM3Ds BLA/CaMKIIα ), we bilaterally infused the virus or its control empty vector virus into the BLA and allowed at least 3 weeks for optimal viral expression ( Figure 1a-c and Supplementary Figure S1a).…”

Section: Chemogenetic Activation Of Gαs Signaling In the Bla Is Suffimentioning

confidence: 99%

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

Siuda

Al‐Hasani

McCall

et al. 2016

Neuropsychopharmacol

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Anxiety disorders are debilitating psychiatric illnesses with detrimental effects on human health. These heightened states of arousal are often in the absence of obvious threatening cues and are difficult to treat owing to a lack of understanding of the neural circuitry and cellular machinery mediating these conditions. Activation of noradrenergic circuitry in the basolateral amygdala is thought to have a role in stress, fear, and anxiety, and the specific cell and receptor types responsible is an active area of investigation. Here we take advantage of two novel cellular approaches to dissect the contributions of G-protein signaling in acute and social anxiety-like states. We used a chemogenetic approach utilizing the Gαs DREADD (rM3Ds) receptor and show that selective activation of generic Gαs signaling is sufficient to induce acute and social anxiety-like behavioral states in mice. Second, we use a recently characterized chimeric receptor composed of rhodopsin and the β 2 -adrenergic receptor (Opto-β 2 AR) with in vivo optogenetic techniques to selectively activate Gαs β-adrenergic signaling exclusively within excitatory neurons of the basolateral amygdala. We found that optogenetic induction of β-adrenergic signaling in the basolateral amygdala is sufficient to induce acute and social anxiety-like behavior. These findings support the conclusion that activation of Gαs signaling in the basolateral amygdala has a role in anxiety. These data also suggest that acute and social anxiety-like states may be mediated through signaling pathways identical to β-adrenergic receptors, thus providing support that inhibition of this system may be an effective anxiolytic therapy.

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“…Here we show that the hM3Dq DREADD (Designer Receptor Exclusively Activated Designer Drug), which is coupled to Gαq signaling pathway and acted as a global neuronal activation tool (Armbruster et al, 2007;Rogan and Roth, 2011), remotely controls DRN serotonergic neurons for both short (hours) and long (weeks) duration studies. We discovered that short-and long-term activation of DRN 5-HT neurons induces both similar and divergent behavioral programs, which mimic multiple actions of antidepressant drugs.…”

Section: Introductionmentioning

confidence: 99%

Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons

Urban

Zhu

Marcinkiewcz

et al. 2015

Neuropsychopharmacol

126

100

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Elucidating how the brain's serotonergic network mediates diverse behavioral actions over both relatively short (minutes-hours) and long period of time (days-weeks) remains a major challenge for neuroscience. Our relative ignorance is largely due to the lack of technologies with robustness, reversibility, and spatio-temporal control. Recently, we have demonstrated that our chemogenetic approach (eg, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) provides a reliable and robust tool for controlling genetically defined neural populations. Here we show how short-and long-term activation of dorsal raphe nucleus (DRN) serotonergic neurons induces robust behavioral responses. We found that both short-and long-term activation of DRN serotonergic neurons induce antidepressant-like behavioral responses. However, only short-term activation induces anxiogenic-like behaviors. In parallel, these behavioral phenotypes were associated with a metabolic map of whole brain network activity via a recently developed non-invasive imaging technology DREAMM (DREADD Associated Metabolic Mapping). Our findings reveal a previously unappreciated brain network elicited by selective activation of DRN serotonin neurons and illuminate potential therapeutic and adverse effects of drugs targeting DRN neurons.

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Remote Control of Neuronal Signaling

Cited by 309 publications

References 170 publications

Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding

Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons

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