A toolkit of highly selective and sensitive genetically encoded neuropeptide sensors

Wang, Huan; Qian, Tong; Zhao, Yingnan; Zhuo, Yizhou; Wu, Chunling; Osakada, Takuya; Chen, Peng; Ren, Huixia; Yan, Yuqi; Geng, Lan; Fu, Shengwei; Mei, Long; Li, Guochuan; Ling, Wu; Jiang, Yi-Wen; Qian, Weiran; Peng, Wanling; Xu, Min; Hu, Ji; Chen, Liangyi; Tang, Chao; Lin, Dayu; Zhou, Jiang‐Ning; Li, Yulong

doi:10.1101/2022.03.26.485911

Cited by 32 publications

(36 citation statements)

References 119 publications

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“…If VIP release is crucial for cAMP rhythms in the SCN, then its release should show circadian oscillations. To determine whether VIP is rhythmically released in the SCN, we introduced a genetically encoded GRAB VIP sensor (GRAB VIP1.0 ) (25). Circularly permutated green fluorescent protein was inserted into VPAC2, and the sensor showed fluorescent changes depending on the extracellular VIP concentration, which allowed us to monitor VIP release or VIP binding to the receptors (Fig.…”

Section: Circadian Camp Rhythms In the Scn Are Driven By Action Poten...mentioning

confidence: 99%

Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus

et al. 2023

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The mammalian central circadian clock, located in the suprachiasmatic nucleus (SCN), coordinates the timing of physiology and behavior to local time cues. In the SCN, second messengers, such as cAMP and Ca 2+ , are suggested to be involved in the input and/or output of the molecular circadian clock. However, the functional roles of second messengers and their dynamics in the SCN remain largely unclear. In the present study, we visualized the spatiotemporal patterns of circadian rhythms of second messengers and neurotransmitter release in the SCN. Here, we show that neuronal activity regulates the rhythmic release of vasoactive intestinal peptides from the SCN, which drives the circadian rhythms of intracellular cAMP in the SCN. Furthermore, optical manipulation of intracellular cAMP levels in the SCN shifts molecular and behavioral circadian rhythms. Together, our study demonstrates that intracellular cAMP is a key molecule in the organization of the SCN circadian neuronal network.

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Section: Circadian Camp Rhythms In the Scn Are Driven By Action Poten...mentioning

confidence: 99%

Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus

et al. 2023

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“…We next used a genetically encoded CRF sensor ( AAV-hSyn-GRAB CRF1.0 ) ( 30 ) to determine the dynamics of CRF release around the PVN (fig. S28D and Fig.…”

Section: Activation Of Vtasst Neurons Suppresses Corticotrophin-relea...mentioning

confidence: 99%

A specific circuit in the midbrain detects stress and induces restorative sleep

Zhao

Wang

et al. 2022

Science

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In mice, social defeat stress (SDS), an ethological model for psychosocial stress, induces sleep. Such sleep could enable resilience, but how stress promotes sleep is unclear. Activity-dependent tagging revealed a subset of ventral tegmental area γ-aminobutyric acid (GABA)–somatostatin (VTA Vgat-Sst ) cells that sense stress and drive non–rapid eye movement (NREM) and REM sleep through the lateral hypothalamus and also inhibit corticotropin-releasing factor (CRF) release in the paraventricular hypothalamus. Transient stress enhances the activity of VTA Vgat-Sst cells for several hours, allowing them to exert their sleep effects persistently. Lesioning of VTA Vgat-Sst cells abolished SDS-induced sleep; without it, anxiety and corticosterone concentrations remained increased after stress. Thus, a specific circuit allows animals to restore mental and body functions by sleeping, potentially providing a refined route for treating anxiety disorders.

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“…Such changes in SST modulation may contribute to dysregulation of PL cortical neurons and outputs and, ultimately be causal to some disease-relevant behaviors. Importantly, the rapid emergence of new optical biosensors for peptides including SST (Xiong et al ., 2021; Wang et al ., 2022) will allow for new in vivo investigation of neurotransmitter versus peptide dynamics. These emerging technologies will allow for the decoupling of SST peptide signaling versus co-released GABA (and potentially other peptides as well).…”

Section: Discussionmentioning

confidence: 99%

Somatostatin peptide signaling dampens cortical circuits and promotes exploratory behavior

Brockway

Moyer

Aloimonos

et al. 2022

Preprint

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BackgroundSomatostatin (SST) neurons in the prelimbic (PL) cortex mediate a variety of behavioral states, ranging from alcohol consumption to fear learning and avoidance-related behaviors. However, little is known about the role of somatostatin peptide signaling itself to cortical functioning and behavior. Here, we sought to characterize the unique physiological and behavioral roles of the SST peptide in the PL cortex.MethodsWe employed a combination of ex vivo electrophysiology, in vivo calcium monitoring, and in vivo peptide pharmacology to explore the role of SST neuron and peptide signaling in the mouse PL cortex. Whole-cell slice electrophysiology was conducted in C57BL/6J male and female mice in pyramidal and GABAergic neurons of the PL cortex to characterize the pharmacological mechanism of SST signaling. Fiber photometry recordings of GCaMP6f fluorescent calcium signals from SST neurons were conducted to characterize the activity profile of SST neurons during exploration of an elevated plus maze (EPM) and open field (OF). We further used local delivery of a broad SST receptor (SSTR) agonist into bilateral PL cortex to test causal effects of SST signaling on these same exploratory behaviors.ResultsSSTR activation broadly hyperpolarized layer 2/3 pyramidal neurons in the PL cortex in both male and female mice ex vivo, through both monosynaptic and polysynaptic GABA neuron-mediated mechanisms of action. This hyperpolarization was blocked by pre-application of the SSTR antagonist cyclo-somatostatin (cyclo-SST) and was non-reversible. SST neurons in PL were activated during EPM and OF exploration, indicating task-related recruitment of these neurons. Lastly, in line with this exploration-related activity profile, SSTR agonist administration directly into the PL enhanced open arm exploration in the EPM.ConclusionsHere we reveal a novel role for the SST peptide system within the PL cortex, by demonstrating a peptide-induced hypoexcitability of PL circuits and modulation of PL-dependent exploratory behaviors.

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A toolkit of highly selective and sensitive genetically encoded neuropeptide sensors

Cited by 32 publications

References 119 publications

Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus

Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus

A specific circuit in the midbrain detects stress and induces restorative sleep

Somatostatin peptide signaling dampens cortical circuits and promotes exploratory behavior

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