bioRxiv Subject Collection: Neuroscience's Journal
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Sunday, April 13th, 2025
| Time |
Event |
| 5:03a |
A ketogenic diet mitigates hippocampal astrogliosis in epileptic brain
The ketogenic diet (KD) is an established treatment for patients with medically intractable epilepsy and is chiefly characterized by high fat/low-carbohydrate intake and the production of ketone bodies (KB) such as {beta}-hydroxybutyrate (BHB). However, after more than a century of clinical use, the mechanisms underlying its efficacy remain unclear. While prior investigations have examined the effects of the KD and its metabolic substrates on synaptic transmission, few studies have explored a potential connection between astrocytic ion channels and seizure genesis. One essential function of astrocytes is spatial potassium buffering which influences passive potassium conductance (PPC), and when impaired, can result in neuronal hyperexcitability. In the present study, we demonstrate that the KD can mitigate hippocampal astrogliosis in the Kcna1-null (KO) mouse model of developmental epilepsy. Specifically, we observed a significant increase in GFAP expression in KO mice fed a control diet compared to wild-type (WT) mice, and that the KD prevented this change. Furthermore, we noted a reduction in hippocampal astrocytic PPC in epileptic mice, whereas KD-treated KO animals exhibited nearly normal passive conductance levels. In this regard, we found that while Kir4.1, TREK-1 and TWIK-1 RNA expression levels were not significantly altered by KD treatment in either WT or KO mice, BHB appeared to only minimally affect Kir4.1-mediated currents in transfected HEK cells. Furthermore, bulk RNA-seq analysis of the various treatment groups revealed KD-induced down-regulation of factors linked to hippocampal astrogliosis. Our findings indicate that the KD protects against epilepsy-associated astrogliosis and astrocytic PPC changes, underscoring a novel mechanism of action, and implicate extracellular potassium in its anti-seizure effects. | | 5:03a |
Construction of Accurate Turtle Cerebellum Models and their use in Simulating Neuromodulation using the BEM-FMM
Digital representations of Purkinje cells from turtle cerebellum, which have long been to study cellular transmission dynamics and neuroplasticity, are necessary to conduct simulations of neuromodulation methods, including Transcranial Magnetic Stimulation (TMS). Methods: Data collected using microCT with 0.6 um isometric resolution are processed, segmented, and arranged to enable high resolution simulation via the Boundary Element Fast Multipole Method. Results: Fully computer aided design compatible, manifold triangular surface meshes were generated from microCT data and used to simulate cellular electromagnetic response to TMS. Conclusion: Accurate Purkinje cells may be readily generated and manipulated to create representative models of turtle cerebellum. Significance: The techniques employed herein may be used to generate accurate surface mesh of Purkinje cells which can enable computational electromagnetics code verification and serve as the basis for skeletal models used for bidomain biophysical simulations in tools such as NEURON to study neurostimulation dynamics and neuromodulation. | | 8:30p |
Attuning to song duels facilitates song-matching in nightingales
Complex vocal communication requires precise, flexible adjustments to vocal-motor commands for the production of coherent responses to auditory inputs. The mechanisms underlying how such sensorimotor integration controls vocal production is poorly understood. Here, we investigate the dynamics of territorial vocal duels and song-matching in common nightingales (Luscinia megarhynchos). Using a combination of field observations, playback experiments and accelerometry, we find that wild nightingales readily modified the acoustic features of their song, matched the rival's song and engaged more vigorously against vocal opponents with a shared song repertoire. Furthermore, we demonstrate that neurons in the sensorimotor nucleus HVC are tuned to specific song stimuli, potentially enabling context-specific integration of auditory information to facilitate matched song production. These findings highlight the crucial role of song recognition in allowing nightingales to adjust their vocalizations in response to specific social situations, demonstrating the complexity and adaptability of their communication system. Moreover, this study provides a new framework and model system for investigating online sensorimotor processing during dynamic vocal interactions. | | 8:30p |
Anterior cingulate cortex mixes retrospective cognitive signals and ongoing movement signatures during decision-making
The anterior cingulate cortex (ACC) is believed to play a key role in reward-based learning in uncertain and dynamic environments. Recent work suggests that in these environments, ACC neurons monitor decisions and their outcomes to inform behavioral strategy. Yet, it remains unclear whether ACC neurons similarly encode behavioral history in fully deterministic perceptual decision-making tasks and, if so, how behavioral history signals interact with other signals that are represented by ACC neurons. Here, we recorded the activity of ACC neurons in freely moving mice performing a visual evidence accumulation task. Many ACC neurons had mixed selectivity: they were strongly driven by non-linear combinations of previous choices and outcomes (trial history). We observed that trial history could be decoded well from the ACC population and that the neural representations of trial history remained stable over multiple seconds. Using linear encoding models, we demonstrate that both trial history and movements strongly drive neural activity in the ACC. We found no relationship between trial history encoding and behavioral biases and instead observed that the neural dynamics encoding trial history were low-dimensional, similar between sessions from the same subjects and conserved across different subjects. These findings suggest the ACC might implement a trial history monitoring process that is independent of behavioral biases and common to different subjects. |
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