Biology subjects

Lavi, A.

Publications and source records attributed to Lavi, A..

7 recordsLinked to original sources

bioRxiv2026

Age-Related Increases in 40Hz Neural Synchrony Are Specific to Typical Development: A Cross-Sectional Study of Autism Spectrum Disorder

Background: The 40Hz auditory steady-state response (ASSR) is a measure of gamma-band neural synchrony sensitive to excitation-inhibition (E/I) balance. Disruptions to E/I balance have been implicated in autism spectrum disorder (ASD), making ASSR an efficient tool for investigating neural synchrony development in this population. Whether age-related differences in 40Hz ASSR are detectable across development in ASD remains understudied. Phelan-McDermid syndrome (PMS), a rare genetic disorder with a phenotype overlapping with autism, caused by SHANK3 disruption, provides a genetically defined model for further investigating E/I-related neural synchrony disruptions. Methods: We examined 40Hz inter-trial phase coherence (ITPC) as an index of neural synchrony across a wide age range (2-37 years) in 127 participants from four groups: TD (n=43), ASD without intellectual disability (w/o ID; n=37), ASD with intellectual disability (w/ID; n=24), and PMS (n=23). Given the distinct age and cognitive profiles of ASD subgroups in this sample, analyses were conducted in separate models: TD vs. ASD w/o ID across all ages, and TD vs. ASD w/ID vs. PMS restricted to participants under 18. Results: For the first time in a cross-sectional sample spanning a large age range, we show that 40Hz ITPC increases significantly with age in TD individuals, while this developmental trajectory is absent in ASD without intellectual disability. Among children and adolescents under 18, 40Hz ITPC did not differ across TD, ASD w/ID, and PMS, and IQ did not predict ITPC in clinical groups. A post-hoc analysis revealed higher ITPC in TD males than females, with no sex differences in ASD or PMS. Conclusions: We demonstrate that gamma-band ITPC trajectories diverge between TD and ASD, specifically in adulthood, with no such difference detectable in childhood. No significant group differences were found among TD, ASD w/ID, and PMS individuals under 18. These findings highlight the importance of age as a critical variable when measuring ASSR, and underscore the need for lifespan studies, particularly in genetically defined conditions such as PMS, to determine whether similar divergence emerges in adulthood.

neuroscience↗

bioRxiv2026

A cortical basis for perception of internal gut sensations

Interoception, the sensing of internal bodily signals, is essential for brain-body interactions and shapes emotion, cognition, and behavior1-5. Subconscious internal signals, including heartbeats or stomach fullness, can rise to conscious awareness, and this process can improve with practice, as seen in meditation, mindful eating, or toilet training in early infancy. Conversely, disrupted interoception is emerging as a common deficit in diverse psychiatric disorders1,3,6,7. Nevertheless, we still lack a fundamental understanding of the neurobiological basis of perception and conscious reporting of internal sensations. Here, we combine genetic and ultra-sensitive optogenetic tools in mice to establish a quantitative framework for studying internal perception. We developed a behavioral task in which mice report detecting non-invasive optogenetic activation of gut mechanosensory neurons, establishing "interoceptive psychophysics". We combine this approach with cellular-resolution imaging and manipulations to reveal the neuronal basis for perception of these internal gut sensations in the interoceptive insular cortex. While representations of sensory stimuli were consistently observed in insular cortex across different tasks, we found that perceptual reports were only encoded during a more difficult psychophysics task, but not during basic detection. Accordingly, manipulation of insular cortex activity affected behavioral reports only in the psychophysics task. These findings reveal a neural basis for perception of internal gut sensations and provide a blueprint for future quantitative exploration of other interoceptive modalities.

neuroscience↗

bioRxiv2025

Insular cortex predictions regulate glucose homeostasis

Brain-body interactions are essential for physical and emotional homeostasis. The brain uses information from the external world to predict upcoming bodily changes. This process involves interoceptive predictions, which are thought to play a central role in brain-body interactions. Yet there is little direct experimental evidence causally linking interoceptive predictions to regulation of bodily physiology. Here we address this by focusing on insular cortex and glucose homeostasis. We find that just before the onset of a meal, insular cortex exhibits a transient burst of activity, reflecting a prediction of the future metabolic state. This transient predictive burst of activity is essential for anticipatory insulin release, subsequent post-meal insulin release, post-meal glucose and lipid homeostasis, and post-meal metabolism signaling in the liver. Our results highlight that insular cortex predictive computations are essential for anticipatory physiological control and for subsequently maintaining metabolic homeostasis.

neuroscience↗

bioRxiv2023

The Effect of Arm Restriction on Dynamic Stability and Upper Body Responses to Lateral Loss of Balance During Walking: An Observational Study

When losing balance, upper-body movements serve as mechanical aids to regain stability. However, it remains unclear how these movements contribute to dynamic stability during recovery from a lateral loss of balance while walking with arm restriction. We aimed to 1) quantify the effect of arm restriction on gait stability and upper-body velocities, and 2) characterize upper-body kinematic strategies in response to lateral surface translations under different arm restriction conditions. Healthy adults were exposed to lateral surface translations while walking on a computerized treadmill under three conditions: free arms, 1-arm restricted and, 2-arms restricted. Dynamic stability and upper-body velocities for the first step after perturbation onset were extracted. We found decreased dynamic stability in the sagittal plane and increased trunk velocity in the 2-arm restricted condition compared to the free arms condition. Head and trunk movements in the mediolateral plane were in opposite directions in 44.31% of responses. Additionally, significant trunk velocities were observed in the opposite direction to the perturbation-induced loss of balance. Our results support the contribution of increased upper-body velocities to balance responses following arm-restricted walking perturbations and suggest that the 2-arm restricted condition may be utilized as a perturbation-based balance training, focusing on head and trunk responses.

neuroscience↗

bioRxiv2021

Co-allocation to overlapping dendritic branches in the retrosplenial cortex integrates contextual memories across time

Events occurring close in time are often linked in memory, providing an episodic timeline and a framework for those memories. Recent studies suggest that memories acquired close in time are encoded by overlapping neuronal ensembles, but the role of dendritic plasticity mechanisms in linking memories is unknown. Using activity-dependent labeling and manipulation approaches, longitudinal one- and two-photon imaging of somatic and dendritic compartments, and computational modeling, we show that memory linking is not only dependent on ensemble overlap in the retrosplenial cortex, but also on branch-specific dendritic allocation mechanisms. The same dendritic segments are preferentially activated by two linked memories, and spine clusters added after each of the two linked memories are allocated to the same dendritic segments. Our results demonstrate a causal mechanistic role for dendritic plasticity in memory integration and reveal a novel set of rules that govern how linked and independent memories are allocated to dendritic compartments.

neuroscience↗

bioRxiv2021

A retrograde mechanism coordinates memory allocation across brain regions

Memories engage ensembles of neurons across different brain regions within a memory system. However, it is unclear whether the allocation of a memory to these ensembles is coordinated across brain regions. To address this question, we used CREB expression to bias memory allocation in one brain region, and rabies retrograde tracing to test memory allocation in connected presynaptic neurons in the other brain regions. We find that biasing allocation of CTA memory in the basolateral amygdala (BLA) also biases memory allocation in presynaptic neurons of the insular cortex (IC). By manipulating the allocation of CTA memory to specific neurons in both BLA and IC, we found that we increased their connectivity and enhanced CTA memory performance. These results - which are corroborated by mathematical simulations, and by studies with auditory fear conditioning - demonstrate that a retrograde mechanism coordinates the allocation of memories across different brain regions.

neuroscience↗

bioRxiv2021

CCR5 closes the temporal window for memory linking

Real world memories are formed in a particular context and are not acquired or recalled in isolation 1-5. Time is a key variable in the organization of memories, since events experienced close in time are more likely to be meaningfully associated, while those experienced with a longer interval are not1-4. How does the brain segregate events that are temporally distinct? Here, we report that a delayed (12-24h) increase in the expression of the C-C chemokine receptor type 5 (CCR5), an immune receptor well known as a co-receptor for HIV infection6,7, following the formation of a contextual memory, determines the duration of the temporal window for associating or linking that memory with subsequent memories. This delayed CCR5 expression in mouse dorsal CA1 (dCA1) neurons results in a decrease in neuronal excitability, which in turn negatively regulates neuronal memory allocation, thus reducing the overlap between dCA1 memory ensembles. Lowering this overlap affects the ability of one memory to trigger the recall of the other, thus closing the temporal window for memory linking. Remarkably, our findings also show that an age-related increase in CCL5/CCR5 expression leads to impairments in memory linking in aged mice, which could be reversed with a CCR5 knockout and an FDA approved drug that inhibits this receptor, a result with significant clinical implications. All together the findings reported here provide the first insights into the molecular and cellular mechanisms that shape the temporal window for memory linking.

neuroscience↗