Transient pre‐seizure inhibition of lateral hypothalamic orexin neurons: a novel possibility for seizure control

MedComm, Год журнала: 2025, Номер 6(2)

Опубликована: Янв. 14, 2025

A recent study published in Nature Communications revealed that the pre-seizure activity of hypocretin/orexin neurons (HONs) lateral hypothalamus (LH) plays a pivotal role determining severity subsequent seizures.1 The temporary inhibition this has been shown to effectively reduce intensity seizures. This offers novel insights into potential strategies for precise seizure prediction and treatment epilepsy. Epilepsy, which is characterized by unpredictable recurrent seizures, one most prevalent severe neurological disorders. However, issues such as poor tolerance adverse effects often impede clinical efficacy chronic anti-seizure medications. HONs globally regulate brain excitability releasing excitatory peptides glutamate, thereby playing crucial roles physiological functions arousal energy metabolism. Previous studies have demonstrated pharmacological suppression promising effects; however, it also leads long-term side effects. Therefore, essential identify specific period HON contributes seizures implement interventions during stage. Initially, Li et al. used mouse optokindling model via optogenetic stimulation glutamatergic CA1 with 20 Hz, 10 s laser stimulation. They reported intraperitoneal administration orexin receptor antagonist SB-334867 reduced susceptibility power without affecting duration; notably decreased spontaneous locomotor mice. Moreover, intracerebroventricular injection was found shorten duration different stages pentylenetetrazol kindling-induced seizures,2 thus indicating distinct properties across various models. Subsequently, calcium fiber photometry monitor activities epochs Compared period, there significant pronounced increase their involvement propagation. Interestingly, be positively correlated preceding onset rather than event itself. Furthermore, multivariate analysis provided additional support notion more intensity. These findings introduce perspective monitoring activity. should noted hippocampal are specifically induced stimulation, differs from observed settings. Future investigations could involve kainic acid- or pilocarpine-induced models further validate correlation between (Figure 1). To investigate causal relationship intensity, optogenetics selectively inhibit bilateral LH time periods. had no effect on severity; at 1 min prior significantly probability, Nevertheless, transient, not exceeding min. In summary, these results suggest acute suppresses Emerging evidence suggests deep (DBS) an alternative therapeutic strategy drug-resistant epilepsy; its closely associated target, employed parameters, epochs. target DBS treatment, applied sinusoid (at either 2 Hz 120 Hz) simultaneously monitored high-frequency (120 hypothalamic (shhDBS) suppressed attenuated whereas low-frequency (2 did any effect. Additionally, conjunction modulation results, only shhDBS performed latency discernible window prolonged compared modulation, evidenced sustained even after DBS. It nonselective technique; specifically, can modulate both cells located upstream projecting pathway fibers. Further warranted elucidate respective Novel tools, including neuromodulator neuropeptide sensors probes, may help verification.3 Another intriguing point respect variability frequency epilepsy regions. (HFS) thalamus reduces frequency,4 (LFS) targeting limbic system structures entorhinal cortex, subiculum, medial septum effect.5 Some suggested HFS induce potentiation, LFS depression. study, (rather LFS) successfully inhibited hyperactivity HONs. explore whether observation related differences electrophysiological characteristics among Finally, basic Epilepsy comorbid neuropsychiatric disorders, anxiety, depression, cognitive impairments, sleep rhythm disturbances. research reverse anxiety-like behaviors worth investigating alleviate comorbidities Taken together, demonstrates promise exert effects, providing approach development treatment. Heming Cheng Yi Wang conceived revisions supervision. Yuang Gu conducted literature research, drafted manuscript, created figures. All authors read approved final manuscript. supported National Natural Science Foundation China (82204353) Zhejiang Province (LY24H310002). declare conflicts interest. Not Applicable.

Язык: Английский

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Live imaging of paracrine signaling: Advances in visualization and tracking techniques

Cell Structure and Function, Год журнала: 2025, Номер 50(1), С. 1 - 14

Опубликована: Янв. 1, 2025

Live imaging techniques have revolutionized our understanding of paracrine signaling, a crucial form cell-to-cell communication in biological processes. This review examines recent advances visualizing and tracking factors through four key stages: secretion from producing cells, diffusion extracellular space, binding to target activation intracellular signaling within cells. Paracrine factor can be directly visualized by fluorescent protein tagging ligand, or indirectly the cleavage transmembrane pro-ligands plasma membrane fusion endosomes comprising factors. Diffusion has been studied using such as fluorescence correlation spectroscopy (FCS), recovery after photobleaching (FRAP), decay photoactivation (FDAP), single-molecule tracking. Binding cells various biosensors, including GPCR-activation-based (GRAB) sensors Förster resonance energy transfer (FRET) probes for receptor tyrosine kinases. Finally, is monitored biosensors second messengers, transcription factors, so on. In addition tools, also highlights emerging optogenetic chemogenetic tools triggering release which essential associating outcomes during bioimaging signaling.Key words: live imaging, optogenetics, chemogenetics.

Язык: Английский

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Illuminating the impact of stress: in vivo approaches to track stress-related neural adaptations.

Neurobiology of Stress, Год журнала: 2025, Номер 35, С. 100712 - 100712

Опубликована: Фев. 7, 2025

Stressful experiences can affect both daily life and long-term health outcomes in a variety of ways. Acute challenges may be adaptive, promoting arousal enhancing memory cognitive function. Importantly, however, chronic stress dysregulates the body's physiological regulatory mechanisms consisting complex hormone interactions throughout peripheral central nervous systems. This disrupted signaling consequently alters balance synapse formation, maturation pruning, processes which regulate neural communication, plasticity, learning, flexibility adaptive behaviors - hallmarks healthy, functional brain. The chronically stressed brain state, therefore, is one uniquely vulnerable. To understand development this how it sustained behavior function are transiently or indelibly impacted by it, we turn to number advanced approaches animal models offer unprecedented insights. has been aim my recent work within field goal new independent research program. achieve this, I have employed methods uncover key circuits integrate information support motivated behaviors, impacts their ability perform process best operationalize behavioral readouts. Here present an overview contributions that find most meaningful for advancing our understanding impact propose avenues will guide own framework address salient outstanding questions field.

Язык: Английский

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Coding principles and mechanisms of serotonergic transmission modes

Molecular Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Язык: Английский

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Principles and Design of Molecular Tools for Sensing and Perturbing Cell Surface Receptor Activity

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Cell-surface receptors are vital for controlling numerous cellular processes with their dysregulation being linked to disease states. Therefore, it is necessary develop tools study and the signaling pathways they control. This Review broadly describes molecular approaches that enable 1) visualization of determine localization distribution; 2) sensing receptor activation permanent readouts as well in real time; 3) perturbing activity mimicking receptor-controlled learn more about these processes. Together, have provided valuable insight into fundamental biology helped characterize therapeutics target receptors.

Язык: Английский

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Recent optical approaches for anatomical and functional dissection of neuron–astrocyte circuitry

The Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Abstract Astrocytes, the most abundant glial cells in brain, are wired into neural circuits through close contact with neuronal pre‐ and post‐synapses, called tripartite synapses. The mutual communication between neurons astrocytes is crucial for circuit dynamics animal behaviour. Recent advancements imaging, manipulation transcriptomics have revealed that exhibit spatiotemporally complex computations represent circuit‐specialised functions molecular makeups. However, understanding neuron–astrocyte circuitry by means of conventional anatomical methods hindered due to technical limitations. In this review, we highlight recently developed optical, genetic viral techniques enable high‐throughput identification connected pairs specificity. These approaches will accelerate functional dissections health disease future studies. image

Язык: Английский

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The brain–heart axis: integrative cooperation of neural, mechanical and biochemical pathways

Nature Reviews Cardiology, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Язык: Английский

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A jack of all trades: Hermaphrodite-specific serotonergic neuron in C. elegans

Journal of Biosciences, Год журнала: 2025, Номер 50(2)

Опубликована: Апрель 16, 2025

Язык: Английский

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Cross-Species Framework for Emotional Well-Being and Brain Aging

JAMA Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Май 7, 2025

Importance Emotional well-being (EWB) is an emerging therapeutic target for managing and preventing symptoms associated with Alzheimer disease related dementias (ADRD). However, more research needed to establish causal inferences between brain changes, EWB, behavioral changes observed in typical aging ADRD. Observations This article presents a framework using cross-species neuroscience approach study EWB aging, adopting well-established biobehavioral model that highlights the reciprocal roles of ADRD symptoms. First, challenges opportunities this field are reviewed. Then, practical solution improve comparability animal human studies proposed. Conclusions Relevance The goal draw comprehensive parallels distinctions could enhance understanding mechanisms linking symptomatic disturbances across different species.

Язык: Английский

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Neuromodulatory processing in the bi-pathway brain architecture

Current Opinion in Neurobiology, Год журнала: 2025, Номер 93, С. 103055 - 103055

Опубликована: Май 23, 2025

Язык: Английский

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