bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown
Опубликована: Авг. 15, 2023
The authors discovered an error in the primary analysis and have withdrawn results from this version of investigation.
Язык: Английский
Cell Reports, Год журнала: 2024, Номер 43(9), С. 114659 - 114659
Опубликована: Авг. 24, 2024
Empathy, crucial for social interaction, is impaired across various neuropsychiatric conditions. However, the genetic and neural underpinnings of empathy variability remain elusive. By combining forward mapping with transcriptome analysis, we discover that aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) a key driver modulating observational fear, basic form affective empathy. Disrupted ARNT2 expression in anterior cingulate cortex (ACC) reduces affect sharing mice. Specifically, selective ablation somatostatin (SST)-expressing interneurons leads to decreased pyramidal cell excitability, increased spontaneous firing, aberrant Ca
Язык: Английский
Процитировано
4
Acta Neuropathologica, Год журнала: 2024, Номер 149(1)
Опубликована: Дек. 17, 2024
In Alzheimer's disease (AD), the propagation and spreading of CNS tau pathology closely correlates with cognitive decline, positioning as an attractive therapeutic target. Amyloid beta (Aβ) has been strongly implicated in driving spread, whereas primary tauopathies such age-related tauopathy (PART)—which lack Aβ pathology—exhibit limited spread minimal-to-no decline. Emerging evidence converges on a trans-synaptic mechanism facilitated by transfer misfolded aggregates (e.g. soluble oligomers). However, it is unclear whether oligomers modulate binding internalization human synapses. Our translationally focused paradigms utilize post-mortem brain specimens from Control, PART, AD patients. Synaptosomes isolated temporal cortex all three groups were incubated preformed recombinant tauO (rtauO), ± AβO (rAβO), oligomer binding/internalization was quantified via flow cytometry following proteinase K (PK) digestion surface-bound oligomers. TauO-synapse interactions visualized using EM immunogold. Brain-derived (BDTO) PART PBS-soluble hippocampal fractions co-immunoprecipitated analyzed mass spectrometry to compare synaptic interactomes secondary tauopathies, thereby inferring role Aβ. synaptosomes, enriched endogenous pathology, exhibited increased rtauO compared synaptosomes. This observation mirrored Control where rAβO significantly internalization. PK pre-treatment abolished this effect, implicating membrane proteins AβO-mediated While both BDTO broadly proteins, differential enrichment endocytic across pre- post-synaptic compartments, showed no significant enrichment. study demonstrates that enhance drive its through proteins. These findings offer novel mechanistic insights underlying pathological directly within synapses emphasize potential targeting Aβ-tau interactions.
Язык: Английский
Процитировано
3
Brain and Behavior, Год журнала: 2025, Номер 15(2)
Опубликована: Фев. 1, 2025
ABSTRACT Background Empathy is an inaccessible part of advanced social cognitive functions in humans. Impairment empathy greatly affects the quality life patients with Parkinson's disease (PD) but underlying neurophysiologic mechanisms have not been established. Objectives The dynamic process brain oscillations PD pain was explored and mechanism damage studied. Methods A total 27 13 healthy controls were recruited to undergo a judgment task, event‐related potentials recorded. This study compared changes theta beta among two groups after presentation painful neutral stimuli. Results Time–frequency analysis results revealed that exhibited oscillation synchronization desynchronization during empathy. Compared controls, reduced magnitude response stimuli attenuated induced by There are abnormal power differences between stimuli, while no found PD. Moreover, positive correlation existed degree associated accuracy judgments. Conclusion Pain deficits modulation oscillations.
Язык: Английский
Процитировано
0
Molecular Brain, Год журнала: 2025, Номер 18(1)
Опубликована: Фев. 25, 2025
Abstract Observational fear (OF) is the ability to vicariously experience and learn from another’s fearful situation, enabling adaptive responses crucial for survival. It has been shown that anterior cingulate cortex (ACC) basolateral amygdala (BLA) are OF. A subset of neurons in ACC activated when observing aversive events demonstrator, which elicits However, neural circuit mechanisms underlying expression OF-related activity remain unexplored. Previous studies have mediodorsal thalamus (MD) OF, MD project ACC. Therefore, we hypothesize projection may facilitate By utilizing vivo calcium imaging combined with optogenetic terminal inhibition MD-ACC pathway, found a was demonstrator’s situation male mice. Furthermore, during moments significantly suppressed Our data suggests plays role neurons.
Язык: Английский
Процитировано
0
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Март 10, 2025
Fear can be induced either directly through self-experience of aversive events or vicariously by observing conspecifics experiencing such events. The locus coeruleus-norepinephrine (LC-NA) system is crucial in fear responses and cognitive processes. We investigated whether the LC-NA differentially processes these two types fear, direct vicarious male mice. results highlighted that right hemisphere LC→anterior cingulate cortex pathway uniquely for while inputs to LC—from bed nucleus stria terminalis (BNST) central amygdala (CeA)—differentially contribute processing. BNST plays a more targeted role CeA has broader influence on general. This underscores complexity specialization within fear-processing. arises vicariously, with involved both. Here, authors show LC → ACC key provide distinct LC, highlighting its complex fear.
Язык: Английский
Процитировано
0
Nature Communications, Год журнала: 2023, Номер 14(1)
Опубликована: Июль 13, 2023
Animals must adapt sensory responses to an ever-changing environment for survival. Such modulation is especially critical in a threatening situation, which animals often promote aversive to, among others, visual stimuli. Recently, threatened Drosophila has been shown exhibit defensive internal state. Whether and how promotes aversion, however, remains elusive. Here we report that mechanical threats transiently gate aversion from otherwise neutral object. We further identified the neuropeptide tachykinin, single cluster of neurons expressing it ("Tk-GAL42 ∩ Vglut neurons"), are responsible gating aversion. Calcium imaging analysis revealed encoded Tk-GAL42 as elevated activity. Remarkably, also discovered object θ oscillation, causally linked Our data reveal organismal response situation through combination rate/temporal coding schemes.
Язык: Английский
Процитировано
6
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июнь 26, 2024
Abstract Left-right asymmetry of the human brain is widespread through its anatomy and function. However, limited microscopic understanding it exists, particularly for anatomical where there are few well-established animal models. In humans, most regions show subtle, population-average regional asymmetries in thickness or surface area, alongside a macro-scale twisting called cerebral petalia which right hemisphere protrudes anteriorly past left. Here, we ask whether neuroanatomical can be observed mice, leveraging 6 mouse neuroimaging cohorts from 5 different research groups (∼3,500 animals). We found an anterior-posterior pattern volume with anterior larger on posterior This appears driven by similar trends area positional asymmetries, results together indicating small brain-wide pattern, to petalia. Furthermore, no apparent relationship known functional emphasizing complexity structure-function asymmetry. By establishing signature aim provide foundation future studies probe mechanistic underpinnings seen humans – feature extremely understanding. Significance Statement The shows significant left-right Understanding basis has implications autism schizophrenia, evolution, embryonic development, between structure function brain. One biggest challenges this aspect that models limited. Here using over 3,500 animals six independent cohorts. These findings mice interrogate roadmap exploring additional species.
Язык: Английский
Процитировано
2
Pain, Год журнала: 2024, Номер unknown
Опубликована: Окт. 1, 2024
Empathy is characterized as the ability to share one's experience and associated with altruism. Previous work using blood oxygen level-dependent (BOLD) functional MRI (fMRI) has found that empathy greater activation in brain mechanisms supporting mentalizing (temporoparietal junction), salience (anterior cingulate cortex; insula), self-reference (medial prefrontal precuneus). However, BOLD fMRI some limitations may not reliably capture tonic of empathy. To address this, present study used a perfusion-based arterial spin labeling approach provides direct quantifiable measurement cerebral flow (1 mL/100 g tissue/min) less susceptible low-frequency fluctuations empathy-based "carry-over" effects be introduced by fMRI-based block designs. Twenty-nine healthy females (mean age = 29 years) were administered noxious heat (48°C; left forearm) during fMRI. In next 2 scans, female volunteers viewed stranger (laboratory technician) their romantic partner, respectively, receive pain-evoking real-time positioned proximal scanner acquisition. Visual analog scale (0 "not unpleasant"; 10 "most unpleasant sensation imaginable") ratings collected after each condition. There was significantly (P 0.01) higher while viewing partner pain right temporoparietal junction, amygdala, anterior insula, orbitofrontal cortex, precuneus when compared stranger. Higher primary visual cortical activation. The findings indicate embodiment another's
Язык: Английский
Процитировано
2
Biological Psychiatry Global Open Science, Год журнала: 2024, Номер 4(4), С. 100315 - 100315
Опубликована: Апрель 3, 2024
Fear responses significantly affect daily life and shape our approach to uncertainty. However, the potential resurgence of fear in unfamiliar situations poses a significant challenge exposure-based therapies for maladaptive responses. Nonetheless, how novel contextual stimuli are associated with relapse extinguished remains unknown. Using context-dependent renewal model, functional circuits underlying mechanisms posterior parietal cortex (PPC) anterior cingulate (ACC) were investigated using optogenetic, histological, vivo, ex vivo electrophysiological pharmacological techniques. We demonstrated that PPC ACC pathway govern context. observed enhanced populational calcium activity neurons received projections from (PPC→ACC) increased synaptic BLA-projecting PPC→ACC upon context, where excitatory postsynaptic currents amplitudes but inhibitory current decreased. In addition, we found parvalbumin (PV)-expressing interneurons (PPC→ACCPV) control renewal, which was blocked by chronic administration fluoxetine. Our findings highlight mediating contexts, contributing insights into intricate neural renewal.
Язык: Английский
Процитировано
1
Advances in neurobiology, Год журнала: 2024, Номер unknown, С. 215 - 234
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
1