Neuromodulator and neuropeptide sensors and probes for precise circuit interrogation in vivo

Science, Год журнала: 2024, Номер 385(6716)

Опубликована: Сен. 26, 2024

To determine how neuronal circuits encode and drive behavior, it is often necessary to measure manipulate different aspects of neurochemical signaling in awake animals. Optogenetics calcium sensors have paved the way for these types studies, allowing perturbation readout spiking activity within genetically defined cell types. However, methods lack ability further disentangle roles individual neuromodulator neuropeptides on behavior. We review recent advances chemical biology tools that enable precise spatiotemporal monitoring control over neuroeffectors their receptors vivo. also highlight discoveries enabled by such tools, revealing molecules signal across timescales learning, orchestrate behavioral changes, modulate circuit activity.

Язык: Английский

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Engineering brain-on-a-chip platforms

Nature Reviews Bioengineering, Год журнала: 2024, Номер 2(8), С. 691 - 709

Опубликована: Июнь 5, 2024

Язык: Английский

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Emerging modes of regulation of neuromodulatory G protein-coupled receptors

Trends in Neurosciences, Год журнала: 2024, Номер 47(8), С. 635 - 650

Опубликована: Июнь 12, 2024

Язык: Английский

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Mu Opioid Receptor–Expressing Neurons in the Dorsal Raphe Nucleus Are Involved in Reward Processing and Affective Behaviors

Biological Psychiatry, Год журнала: 2023, Номер 94(11), С. 842 - 851

Опубликована: Июнь 5, 2023

Язык: Английский

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Endogenous opiates and behavior: 2023

Peptides, Год журнала: 2024, Номер 179, С. 171268 - 171268

Опубликована: Июнь 28, 2024

Язык: Английский

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Photoswitchable Carbamazepine Analogs for Non‐Invasive Neuroinhibition In Vivo

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(38)

Опубликована: Июнь 18, 2024

A problem of systemic pharmacotherapy is off-target activity, which causes adverse effects. Outstanding examples include neuroinhibitory medications like antiseizure drugs, are used against epilepsy and neuropathic pain but cause side There a need drugs that inhibit nerve signals locally on-demand without affecting other regions the body. Photopharmacology aims to address this with light-activated localized illumination in target organ. Here, we have developed photoswitchable derivatives widely prescribed drug carbamazepine. For purpose, expanded our method ortho azologization tricyclic meta/para N-bridged diazocine. Our results validate concept cryptoazologs (uniquely exemplified by Carbazopine-1) bring light Carbadiazocine (8), can be photoswitched between 400-590 nm (using violet LEDs halogen lamps) shows good drug-likeness predicted safety. Both compounds display activity vitro translucent zebrafish larvae. (8) also offers vivo analgesic efficacy (mechanical thermal stimuli) rat model simple compelling treatment demonstration non-invasive illumination.

Язык: Английский

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Top-down control of the descending pain modulatory system drives placebo analgesia

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 16, 2025

In placebo analgesia, prior experience and expectations lead to pain suppression by the administration of an inert substance, but causal evidence for its neural basis is lacking. To identify underlying circuits, we reverse-translated a conditioned protocol from humans mice. Surprisingly, effect suppresses both nociception unconditioned emotional-motivational pain-related behavior. Descending modulatory neurons in periaqueductal gray (PAG) are critical morphine antinociception. The depends on input PAG medial prefrontal anterior cingulate cortices, not insular cortex. Conditioning enhances noxious stimulus-evoked endogenous opioid release produce analgesia. Our results suggest that cortical control descending system (DPMS) gated rapid signaling during trials. This study bridges clinical preclinical research, establishing central role DPMS

Язык: Английский

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Conceptual expansion of photomedicine for spatiotemporal treatment methods

RSC Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

This review covers the history of light therapy, emergence photopharmacology, its methods, and challenges. Current advancements show promise for treating diseases like cancer with precision minimal side effects.

Язык: Английский

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Photopharmacological activation of adenosine A1 receptor signaling suppresses seizures in a mouse model for temporal lobe epilepsy

Journal of Controlled Release, Год журнала: 2025, Номер unknown, С. 113626 - 113626

Опубликована: Март 1, 2025

Up to 30 % of epilepsy patients suffer from drug-resistant (DRE). The search for innovative therapies is therefore important close the existing treatment gap in these patients. adenosinergic system possesses potent anticonvulsive effects, mainly through adenosine A1 receptor (A1R). However, clinical application A1R agonists hindered by severe systemic side effects. To achieve local modulation A1Rs, we employed a photopharmacological approach using caged version agonist N6-cyclopentyladenosine, termed cCPA. We performed first vivo study with intracerebroventricularly (ICV) administered cCPA investigate potential photo-uncage and release sufficient amounts hippocampus illumination order suppress hippocampal excitability seizures mice. validated presence after ICV injection explored its pharmacokinetic profile stability. Using evoked recordings, showed reduction neurotransmission photo-releasing CPA, similar that obtained CPA. Furthermore, intrahippocampal kainic acid mouse model DRE, photo-release CPA epileptic resulted strong suppression seizures. Finally, demonstrated less impairment motor performance rotarod test compared administration These results provide proof concept as an effective precision DRE.

Язык: Английский

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A Bright Future for Photopharmaceuticals Addressing Central Nervous System Disorders: State of the Art and Challenges Toward Clinical Translation

Medicinal Research Reviews, Год журнала: 2025, Номер unknown

Опубликована: Апрель 5, 2025

ABSTRACT Photopharmacology is an innovative approach that uses light to activate drugs. This method offers the potential for highly localized and precise drug activation, making it particularly promising treatment of neurological disorders. Despite enticing prospects photopharmacology, its application treat human central nervous system (CNS) diseases remains be demonstrated. In this review, we provide overview prominent strategies design activation photopharmaceutical agents in field neuroscience. Photocaged photoswitchable drugs bioactive molecules are discussed, instructive list examples provided highlight compound strategies. Special emphasis placed on photoactivatable compounds modulation glutamatergic, GABAergic, dopaminergic, serotonergic neurotransmission conditions, as well various photoresponsive with improved pain management. Compounds holding promise clinical translation discussed in‐depth their future applications assessed. Neurophotopharmaceuticals have yet achieve breakthrough clinic, both delivery not reached full maturity. However, by describing current state art providing illustrative case studies, offer a perspective opportunities neurophotopharmacology focused addressing CNS

Язык: Английский

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