Bmal1 haploinsufficiency impairs fear memory and modulates neuroinflammation via the 5-HT2C receptor DOI Creative Commons
Weifen Li,

Shengnan Mou,

Tahir Ali

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 14, 2024

Background BMAL1, a key regulator of circadian rhythms, plays multifaceted role in brain function. However, the complex interplay between memory, neuroinflammation, and neurotransmitter regulation remains poorly understood. To investigate these interactions, we conducted study using BMAL1-haplodeficient mice (BMAL1 +/− ). Methods We exposed BMAL1 to behavioral assessments including cued fear conditioning, new objection recognition (NOR) test, Y-maze test evaluate haplodeficiency impact on memory. Furthermore, biochemical changes were analyzed through western blotting, ELISA explore further mechanism neuroinflammation. Results found that haploinsufficiency led deficits learning while spatial memory object remained intact. Further analysis revealed dysregulated levels alterations neurotransmitter-related proteins prefrontal cortex mice. Pharmacological interventions targeting dopamine uptake or 5-HT2C receptor demonstrated inhibiting could rescue impairments Additionally, observed downregulation inflammasome neuroinflammation pathways mice, which is validated by inflammation mediator lipopolysaccharide (LPS) administration. Conclusion These findings highlight leads are linked neurotransmitters receptors, particularly receptor. Targeting may offer potential therapeutic strategy for mitigating cognitive associated with dysfunction.

Language: Английский

Prey capture learning drives critical period-specific plasticity in mouse binocular visual cortex DOI Creative Commons
Diane Bissen, Brian Cary, Amanda Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Summary Critical periods are developmental windows of high experience-dependent plasticity essential for the correct refinement neuronal circuitry and function. While consequences visual system sensory deprivation during critical period have been well-characterized, far less is known about effects enhanced experience. Here, we use prey capture learning to assess structural functional mediating in primary cortex mice. We show that improves temporal frequency discrimination drives a profound remodeling through an increase excitatory connectivity spine turnover. This global persistent rewiring not observed adult hunters mediated by TNFα-dependent mechanisms. Our findings demonstrate experience naturalistic paradigm can drive improve function, promotes long-lasting dynamics could enhance subsequent plasticity.

Language: Английский

Citations

3
Cognitive integrity in Non‐Demented Individuals with Alzheimer's Neuropathology is associated with preservation and remodeling of dendritic spines DOI Creative Commons

Jutatip Guptarak,

Pietro Scaduto,

Batbayar Tumurbaatar

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(7), P. 4677 - 4691

Published: June 3, 2024

Individuals referred to as Non-Demented with Alzheimer's Neuropathology (NDAN) exhibit cognitive resilience despite presenting disease (AD) histopathological signs. Investigating the mechanisms behind this may unveil crucial insights into AD resistance.

Language: Английский

Citations

7
Anatomical restructuring of a lateralized neural circuit during associative learning by asymmetric insulin signaling DOI Creative Commons
Leo T. H. Tang, Garrett Lee, Steven J. Cook

et al.

Current Biology, Journal Year: 2023, Volume and Issue: 33(18), P. 3835 - 3850.e6

Published: Aug. 16, 2023

Language: Английский

Citations

10
Structural synaptic signatures of contextual memory retrieval-reactivated hippocampal engram cells DOI Creative Commons

Panthea Nemat,

Salimat Semenova,

Rolinka J. van der Loo

et al.

Neurobiology of Learning and Memory, Journal Year: 2025, Volume and Issue: unknown, P. 108033 - 108033

Published: Feb. 1, 2025

Language: Английский

Citations

0
Unraveling the mysteries of dendritic spine dynamics: Five key principles shaping memory and cognition DOI Creative Commons
Haruo Kasai

Proceedings of the Japan Academy Series B, Journal Year: 2023, Volume and Issue: 99(8), P. 254 - 305

Published: Oct. 10, 2023

Recent research extends our understanding of brain processes beyond just action potentials and chemical transmissions within neural circuits, emphasizing the mechanical forces generated by excitatory synapses on dendritic spines to modulate presynaptic function. From in vivo vitro studies, we outline five central principles synaptic mechanics function: P1: Stability - Underpinning integral relationship between structure function spine synapses. P2: Extrinsic dynamics Highlighting synapse-selective structural plasticity which plays a crucial role Hebbian associative learning, distinct from pathway-selective long-term potentiation (LTP) depression (LTD). P3: Neuromodulation Analyzing G-protein-coupled receptors, particularly dopamine time-sensitive modulation learning frameworks such as Pavlovian classical conditioning Thorndike's reinforcement (RL). P4: Instability Addressing intrinsic memory management during continual spotlighting their "spine dysgenesis" associated with mental disorders. P5: Mechanics Exploring how influence both sides establish traces short- memory, thereby aiding integration functions. We also delve into historical background foresee impending challenges.

Language: Английский

Citations

5
A dendrite is a dendrite is a dendrite? Dendritic signal integration beyond the “antenna” model DOI Creative Commons
Moritz Stingl, Andreas Draguhn, Martin Both

et al.

Pflügers Archiv - European Journal of Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 9, 2024

Neurons in central nervous systems receive multiple synaptic inputs and transform them into a largely standardized output to their target cells-the action potential. A simplified model posits that signals are integrated by linear summation passive propagation towards the axon initial segment, where threshold for spike generation is either crossed or not. However, lines of research during past decades have shown signal integration individual neurons much more complex, with important functional consequences at cellular, network, behavioral-cognitive level. The interplay between concomitant excitatory inhibitory postsynaptic potentials depends strongly on relative timing localization respective synapses. In addition, dendrites contain voltage-dependent conductances, which allow scaling potentials, non-linear input processing, compartmentalization signals. Together, these features enable rich variety single-neuron computations, including operations plasticity. Hence, we revise over-simplified messages from textbooks use computational models like integrate-and-fire some caution. This concept article summarizes most mechanisms dendritic highlights recent developments field.

Language: Английский

Citations

1
Differential expression of genes in the RhoA/ROCK pathway in the hippocampus and cortex following intermittent hypoxia and high intensity interval training. DOI
Natalie E. Doody, Nicole J. Smith, Elizabeth C. Akam

et al.

Journal of Neurophysiology, Journal Year: 2024, Volume and Issue: 132(2), P. 531 - 543

Published: Aug. 1, 2024

Intermittent hypoxia (IH) and high-intensity interval training (HIIT) enhance neuroplasticity upregulate neurotrophic factors in the central nervous system (CNS). We provide evidence that IH + HIIT also have capacity to regulate genes involved RhoA/ROCK signaling pathway is known restrict structural plasticity CNS. This provides a new mechanistic insight into how these interventions may hippocampal-related facilitate learning, memory, neuroregeneration.

Language: Английский

Citations

1
Prenatal exposure of azadiradione leads to developmental disabilities DOI Creative Commons

Sudipta Jana,

Sagarika Das,

Bhaskarjyoti Giri

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 11, 2024

Abstract Azadiradione is a brain permeable phytochemical present in the seed of an Indian medicinal plant, Azadirachta Indica, well-known as Neem. Recently, this small bioactive molecule has been revealed to induce expression Ube3a, ubiquitin ligase whose loss and gain function associated with two diverse neurodevelopmental disorders. Here we report that in uteroexposure azadiradione mice result severe developmental disabilities. Treatment well tolerated dose into pregnant dam (at embryonic day 12 14) causes substantial decrease body weight new-born pups at their early periods along significant cognitive, motor communication deficits increased anxiety-like behaviours. As animals grow from adolescent adult, many behavioural are gradually restored normalcy, although, cognitive deficit persists significantly. Biochemical analysis reveals prenatally exposed exhibits about 2-3 fold increase level Ube3a post natal 25 some its target proteins linked synaptic plasticity indicating enduring effect drug on expression. The also display number dendritic spines hippocampal cortical pyramidal neurons. These results suggest might be one key players azadiradione-induced

Language: Английский

Citations

0
KETAMINE: Neural- and network-level changes DOI
Vishal Bharmauria, Hamidreza Ramezanpour,

Afef Ouelhazi

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 559, P. 188 - 198

Published: Sept. 7, 2024

Language: Английский

Citations

0
Prenatal Exposure to Azadiradione Leads to Developmental Disabilities DOI

Sudipta Jana,

Sagarika Das,

Bhaskarjyoti Giri

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Language: Английский

Citations

0