Heterogeneity of anti-Caspr2 antibodies: specificity and pathogenicity

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

Опубликована: Янв. 21, 2025

ABSTRACT Maternal anti-Caspr2 (Contactin-associated protein-like 2) antibodies have been associated with increased risk for autism spectrum disorder (ASD). Previous studies shown that in utero exposure to results a phenotype ASD-like features male mice. Here we ask whether four newly generated against Caspr2 are pathogenic the developing fetal brain and they function through similar means. Our show novel recognize different epitopes of Caspr2. In these elicits differential phenotypes offspring, tested social interaction, open field, light-dark tasks. These demonstrate variability antigenic specificity pathogenicity which may clinical implications.

Язык: Английский

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Cholecystokinin facilitates the formation of long-term heterosynaptic plasticity in the distal subiculum

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Фев. 1, 2025

It has been well established that Cornu Ammonis-(CA1) and subiculum (SUB) serve as the major output components of entorhinal-hippocampal circuitry. Nevertheless, how neuromodulators regulate neurocircuitry in hippocampal formation remained elusive. Cholecystokinin (CCK), is most abundant neuropeptide central nervous system, which broadly regulates animal's physiological status at multiple levels, including neuroplasticity its behavioral consequences. Here, we uncover exogenous CCK potentiates excitatory synaptic transmission CA1-SUB projections via CCK-B receptor. Dual-color light theta burst stimulation elicits heterosynaptic long-term potentiation distal SUB region. Light activation medial entorhinal cortex (MEC) derived CCK-positive neurons triggers release SUB. Neuronal activities SUB-projecting MECCCK are necessary for conveying processing navigation-related information. In conclusion, our findings prove a crucial role regulating neurobiological functions from modulates plasticity CA1-subiculum pathway information wild-type mice.

Язык: Английский

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MCU expression in hippocampal CA2 neurons modulates dendritic mitochondrial morphology and synaptic plasticity

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 6, 2025

Abstract Neuronal mitochondria are diverse across cell types and subcellular compartments in order to meet unique energy demands. While essential for synaptic transmission plasticity, the mechanisms regulating support normal synapse function incompletely understood. The mitochondrial calcium uniporter (MCU) is proposed couple neuronal activity ATP production, which would allow neurons rapidly adapt changing MCU uniquely enriched hippocampal CA2 distal dendrites compared proximal dendrites, however, functional significance of this layer-specific enrichment not clear. Synapses onto readily express unlike plasticity-resistant synapses but underlying these different plasticity profiles unknown. Using a CA2-specific knockout (cKO) mouse, we found that deletion impairs at dendrite synapses. However, were more fragmented spine head area was diminished throughout dendritic layers cKO mice versus control mice. Fragmented might have changes, such as altered could explain structural deficits Differences expression circuits be general mechanism tune distinct

Язык: Английский

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Essential Role of the Anterior Piriform Cortex in Mediating Social Novelty Output via a Top–Down Circuit

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Abstract Social novelty is indispensable for a wide range of social behaviors. The medial prefrontal cortex (mPFC), along with other information hubs, composes the foundational circuitry novelty. However, precise circuit mechanisms that govern processing remain elusive. piriform cortex, as largest olfactory receives extensive innervation from top‐down centers dictate behavior. Here, it shown anterior (APC) exhibited an increase in gamma event incidence during engagement male mice. In vivo electrophysiology and fiber photometry reveal APC pyramidal neurons respond more intensely to novel mice than familiar ones. Intriguingly, silencing selectively impairs processing, yet leaves basic discrimination capabilities intact. Moreover, inherits cues mPFC sends feedback projections bulb (OB) modulate These findings unveil APC's role extending well beyond olfaction, encompassing specialized function recognition

Язык: Английский

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Oxytocin modulates inhibitory balance in the prelimbic cortex to support social memory consolidation during REM sleep

Theranostics, Год журнала: 2025, Номер 15(8), С. 3257 - 3274

Опубликована: Фев. 18, 2025

Rationale: The prelimbic cortex (PrL), enriched with oxytocin (OXT) receptors, plays a critical role in memory consolidation. However, the of OXT social consolidation within PrL microcircuit remains poorly understood. Methods: To examine signaling consolidation, we used biosensors and loss-of-function approaches, including tetanus toxin-mediated silencing neurons paraventricular nucleus (PVNOXT), optogenetic inhibition PVNOXT-PrL pathway during rapid-eye-movement (REM) sleep, local administration an receptor antagonist PrL. In vivo molecular for vasoactive intestinal peptide (VIP), somatostatin, presynaptic calcium imaging were employed to assess inhibitory microcircuit. Optogenetic activation intranasal evaluate resilience chronic sleep deprivation-induced deficits. Results: We identified that REM-sleep release via PVN supports deficiency reduces activity VIP parvalbumin (PV) neurons, thereby disrupting balance between somatic mediated by PV dendritic disinhibition microcircuits REM sleep. Chronic deprivation (SD) disrupts balance, leading pyramidal neuron hyperactivity impairments. Notably, REM-sleep-specific or restores rescues deficits SD mice. Conclusion: Our results reveal how modulates support suggesting potential therapeutic strategies treating sleep-related disorders.

Язык: Английский

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