Entorhinohippocampal cholecystokinin modulates spatial learning by facilitating neuroplasticity of hippocampal CA3-CA1 synapses DOI Creative Commons
Junfeng Su, Fengwen Huang, Tian Yu

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(12), P. 113467 - 113467

Published: Nov. 17, 2023

The hippocampus is broadly impacted by neuromodulations. However, how neuropeptides shape the function of and related spatial learning memory remains unclear. Here, we discover crucial role cholecystokinin (CCK) in heterosynaptic neuromodulation from medial entorhinal cortex (MEC) to hippocampus. Systematic knockout CCK gene impairs CA3-CA1 LTP space-related performance. MEC provides most CCK-positive neurons projecting hippocampal region, which potentiates long-term plasticity heterosynaptically a frequency- NMDA receptor (NMDAR)-dependent manner. Selective inhibition CCKergic or downregulation their mRNA levels also formation animals' performance water maze. This excitatory extrahippocampal projection releases upon high-frequency excitation active during animal exploration. Our results reveal critical projections bridging intra- circuitry at electrophysiological behavioral levels.

Language: Английский

Multisensory gamma stimulation promotes glymphatic clearance of amyloid DOI Creative Commons
Mitchell H. Murdock,

Cheng-Yi Yang,

Na Sun

et al.

Nature, Journal Year: 2024, Volume and Issue: 627(8002), P. 149 - 156

Published: Feb. 28, 2024

Abstract The glymphatic movement of fluid through the brain removes metabolic waste 1–4 . Noninvasive 40 Hz stimulation promotes neural activity in multiple regions and attenuates pathology mouse models Alzheimer’s disease 5–8 Here we show that multisensory gamma influx cerebrospinal efflux interstitial cortex 5XFAD model disease. Influx was associated with increased aquaporin-4 polarization along astrocytic endfeet dilated meningeal lymphatic vessels. Inhibiting clearance abolished removal amyloid by stimulation. Using chemogenetic manipulation a genetically encoded sensor for neuropeptide signalling, found vasoactive intestinal peptide interneurons facilitate regulating arterial pulsatility. Our findings establish novel mechanisms recruit system to remove amyloid.

Language: Английский

Citations

99

Prolonged sleep deprivation induces a cytokine-storm-like syndrome in mammals DOI Creative Commons
Di Sang,

Keteng Lin,

Yini Yang

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(25), P. 5500 - 5516.e21

Published: Nov. 27, 2023

Language: Английский

Citations

75

Unlocking opioid neuropeptide dynamics with genetically encoded biosensors DOI Creative Commons
Chunyang Dong, Raajaram Gowrishankar, Yihan Jin

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(9), P. 1844 - 1857

Published: July 15, 2024

Abstract Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for precise dissection their complex and diverse dynamics circuit-specific manner. Opioid peptides modulate pain, reward aversion as such have high clinical relevance. To illuminate spatiotemporal endogenous opioid signaling brain, we developed class genetically encoded fluorescence sensors based on kappa, delta mu receptors: κLight, δLight µLight, respectively. We characterized pharmacological profiles these mammalian cells dissociated neurons. used κLight to identify electrical stimulation parameters trigger release scale dynorphin volume transmission brain slices. Using vivo fiber photometry mice, demonstrated utility detecting optogenetically driven observed differential response fearful rewarding conditions.

Language: Английский

Citations

20

Real‐time detection of somatostatin release from single islets reveals hypersecretion in type 2 diabetes DOI Creative Commons
Mingyu Yang,

Kousik Mandal,

Moa Södergren

et al.

Acta Physiologica, Journal Year: 2025, Volume and Issue: 241(2)

Published: Jan. 13, 2025

Somatostatin from pancreatic δ-cells is a paracrine regulator of insulin and glucagon secretion, but the release kinetics whether secretion altered in diabetes unclear. This study aimed to improve understanding somatostatin by developing tool for real-time detection individual islets. Reporter cells responding with cytoplasmic Ca2+ concentration ([Ca2+]i) changes were generated co-expressing receptor SSTR2, G-protein Gα15 fluorescent sensor HeLa cells. induced dose-dependent [Ca2+]i increases reporter half-maximal maximal effects at 1.6 ± 0.4 ~30 nM, respectively. Mouse human islets cell elevations that inhibited SSTR2 antagonist CYN154806. Depolarization high K+, KATP channel blockade or increasing glucose 3 11 mM evoked concomitant Exposure glucagon, GLP-1 ghrelin also triggered responses, whereas little effect was obtained islet exposure insulin, glutamate, GABA urocortin-3. Islets type 2 diabetic donors higher responses after K+ depolarization compared non-diabetic islets, although fewer identified immunostaining. Type associated hypersecretion somatostatin, which has implications regulation secretion. The new assay single-islet holds promise further studies physiology pathophysiology.

Language: Английский

Citations

2

A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release DOI Creative Commons
Xiju Xia, Yulong Li

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 18, 2025

The co-existence and co-transmission of neuropeptides small molecule neurotransmitters within individual neuron represent a fundamental characteristic observed across various species. However, the differences regarding their in vivo spatiotemporal dynamics underlying molecular regulation remain poorly understood. Here, we develop GPCR-activation-based (GRAB) sensor for detecting short neuropeptide F (sNPF) with high sensitivity resolution. Furthermore, investigate between sNPF acetylcholine (ACh) from same neurons. Interestingly, our findings reveal distinct release ACh. Notably, results indicate that synaptotagmins (Syt) are involved these two processes, as Syt7 Sytα release, while Syt1 ACh release. Thus, this high-performance GRAB provides robust tool studying shedding insights into unique distinguish neurotransmitters.

Language: Английский

Citations

2

Corticotropin-releasing hormone signaling from prefrontal cortex to lateral septum suppresses interaction with familiar mice DOI Creative Commons
Noelia S. de León-Reyes, Paula Sierra Díaz, Ramon Nogueira

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(19), P. 4152 - 4171.e31

Published: Sept. 1, 2023

Language: Английский

Citations

35

Presynaptic sensor and silencer of peptidergic transmission reveal neuropeptides as primary transmitters in pontine fear circuit DOI
Dongil Kim, Sekun Park, S. Park

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(18), P. 5102 - 5117.e16

Published: July 22, 2024

Language: Английский

Citations

11

NIR‐Excitable POM‐Encapsulated Yb‐Bi2S3 Decorated Graphene for Wearable Photoelectrochemical Sensing DOI
Han Wang,

Caoling Li,

Jingwei Zhang

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(25)

Published: Feb. 16, 2024

Abstract Transition metal sulfides have garnered significant interest in the realm of photoelectrochemical (PEC) sensors due to their remarkable optical and electrical properties. However, intrinsic UV–vis adsorption electron‐donor consumption severely hinder nonirritating situ epidermal PEC applications. Herein, a NIR‐808 nm light‐excited heterojunction, phosphomolybdic acid‐encapsulated ytterbium‐doped bismuth sulfide (Yb‐Bi 2 S 3 /PMA), is synthesized by hydrothermal method for self‐sufficient electron donor‐based sensing. Further, Yb‐Bi /PMA heterojunction decorated on flexible integrated laser‐induced graphene electrode arrays, providing ultrafast charge carrier transfer capacity robust mechanical durability (300 bending cycles) subsequent wearable As showcase, aptamer molecular recognition‐based sensor sweat trace Neuropeptide Y (NPY, stress or depression biomarker) presents an ultra‐low detection limit (0.39 fM) good anti‐interference ability. Moreover, integration aptasensor with signal processing wireless communication facilitates analysis NPY dynamics various real scenarios (feeding behaviors, physiological stress, circadian rhythm). More broadly, this research establishes foundation NIR‐excitable semiconductors equipped donor capabilities, unlocking potential ultrasensitive sensing

Language: Английский

Citations

10

Neuromodulator and neuropeptide sensors and probes for precise circuit interrogation in vivo DOI
Jessie Muir, Maribel Anguiano, Christina K. Kim

et al.

Science, Journal Year: 2024, Volume and Issue: 385(6716)

Published: Sept. 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.

Language: Английский

Citations

10

Stochastic neuropeptide signals compete to calibrate the rate of satiation DOI
Stephen X. Zhang, Angela Kim,

Joseph C. Madara

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Language: Английский

Citations

10