bioRxiv Subject Collection: Neuroscience's Journal
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Thursday, January 16th, 2025
| Time |
Event |
| 10:32a |
Experience directs the instability of neuronal tuning for critical period plasticity in mouse visual cortex
Brief monocular deprivation during a developmental critical period, but not thereafter, alters the receptive field properties (tuning) of neurons in visual cortex, but the characteristics of neural circuitry that permit this experience-dependent plasticity are largely unknown. We performed repeated calcium imaging at neuronal resolution to track the tuning properties of populations of excitatory layer 2/3 neurons in mouse visual cortex during or after the critical period, as well as in nogo-66 receptor (ngr1) mutant mice that sustain critical-period plasticity as adults. The instability of tuning for populations of neurons was greater in juvenile mice and adult ngr1 mutant mice. We propose instability of neuronal tuning gates plasticity and is directed by experience to alter the tuning of neurons during the critical period. | | 10:32a |
Cortical travelling waves may underpin variation in personality traits
Objectives: Personality traits must relate to stable neural processes, yet few robust neural correlates of personality have been discovered. Recent methodological advances enable measurement of cortical travelling waves, which likely underpin information flow between brain regions. Here, we explore whether cortical travelling waves relate to personality traits from the "Big Five" taxonomy. Method: We assessed personality traits and recorded resting electroencephalography (EEG) from 300 participants. We computed travelling wave strength using a 3D fast Fourier transform and explored relationships between alpha travelling waves and personality traits. Results: Trait Agreeableness and Openness/Intellect had significant relationships to travelling waves that passed multiple-comparison controls (pFDR = 0.019, pFDR = 0.036). Agreeableness related to interhemispheric waves travelling from the right hemisphere along central lines (rho = 0.263, p < 0.001, BF10 = 356.350). This relationship was unique to the compassion aspect (t = 3.719, p <0.001) rather than politeness aspect of Agreeableness (t = 0.897, p = 0.370). Openness/Intellect related to backwards travelling waves along midline electrodes (rho = 0.197, p < 0.001, BF10 = 13.800), which was confirmed for the Openness aspect (rho = 0.216, p < 0.001, BF10 = 26.444) but not the Intellect aspect (rho = 0.093, p = 0.109, BF10 = 0.344). Conclusions: Greater cortical travelling wave strength from right temporal regions may partly underpin variation in trait compassion, and backwards travelling wave strength along midline electrodes may mark trait openness. Further research is needed to investigate the mechanistic role of travelling waves in personality traits and other individual differences. | | 10:32a |
Stress-activated neuronal ensemble in the supramammillary nucleus stores anxiety but not memory
Anxiety is a very common negative emotional status induced by stress. However, its underlying neural mechanism is still largely unknown. Here, we found a hypothalamic section named the supramammillary nucleus (SuM), which is taking control of anxiety. We then characterized a small ensemble of stress-activated neurons and recruited encoding anxiety. These stress-activated neurons specifically respond to stress, and its activation robustly increases the anxiety-like behavior of mice without significantly influencing fear memory. We then found that the ventral subiculum -SuM but not the dorsal subiculum -SuM projection encodes anxiety and would exhibit an anti-anxiety effect by its inhibition. Our findings extend the understanding of the function of the neuronal engram cells and bring new insights into the studies on emotion especially anxiety. | | 11:00a |
Self-organization of high-dimensional geometry of neural activity in culture
A vast number of neurons exhibit high-dimensional coordination for brain computation, both in processing sensory input and in generating spontaneous activity without external stimuli. Recent advancements in large-scale recordings have revealed that this high-dimensional population activity exhibits a scale-free structure, characterized by power law and distinct spatial patterns in principal components (PCs). However, the mechanisms underlying the formation of this high-dimensional neural coordination remain poorly understood. Specifically, it is unclear whether the characteristic high-dimensional structure of population activity emerges through self-organization or is shaped by the learning of sensory stimuli in animals. To address this question and clearly differentiate between these two possibilities, we investigated large-scale neural activity in dissociated neuronal culture using high-density multi-electrode arrays. Our findings demonstrate that the high-dimensional structure of neural activity self-organizes during network development in the absence of explicit sensory stimuli provided to animals. As the cultures mature, the PC variance exhibits a power-law decay, and the spatial structures of PCs transition from global to localized patterns, driven by the temporal correlations of neural activity. Furthermore, we observed an unexpected co-occurrence between the power-law decay in PCA and neuronal avalanches, suggesting a link between self-organized criticality and high-dimensional activity. Using a recurrent neural network model, we show that both phenomena can arise from biologically plausible heavy-tailed synaptic connectivity. By highlighting a developmental origin of the high-dimensional structure of neural activity, these findings deepen our understanding of how coordinated neural computations are achieved in the brain. | | 10:02p |
Linalool and trans-nerolidol prevent pentylenetetrazole-induced seizures in adult zebrafish
Ethnopharmacological relevance: linalool (LIN) and trans-nerolidol (NER) are terpene alcohols found in high concentrations in plant-derived essential oils used as a traditional treatment in many cultures. Several studies evaluating the effects of these essential oils and their isolated compounds have shown antiseizure, sedative, neuroprotective, and antioxidant properties in acute seizure models both in vitro and in vivo. Therefore, this study aimed to evaluate the effects of acute exposure to LIN or NER on a pentylenetetrazole (PTZ)-induced seizure model in adult zebrafish (Danio rerio). Methods: 240 adult wild-type zebrafish were randomly allocated to the experimental groups: control (dechlorinated water), 1% DMSO (vehicle), diazepam (50 M DZP), and LIN or NER (4, 40 and 400 M). Animals were exposed to the treatment solution (400 mL) for 10 minutes, taken to a washout beaker (dechlorinated water, 400 mL) for 5 minutes, and recorded in the test apparatus containing 10 mM PTZ for 20 minutes. Experienced researchers conducted a blinded analysis of behavioral seizure phenotypes using BORIS software. Additionally, locomotor activity was evaluated through ANY-Maze tracking software, ensuring precise and unbiased assessment of movement behaviors. Results: the highest concentration of LIN (400 M) and NER (40 and 400 M) increased the latency to reach clonic and tonic-like seizure stages while decreasing the seizure intensity. Interestingly, NER has shown a larger effect size than the positive control group DZP, and at a concentration of 40 M, increased locomotor behavior. Conclusion: our findings show the antiseizure properties of LIN and NER in zebrafish acutely exposed to PTZ, delaying the time to reach the highest seizure stages and decreasing seizure intensity. These results are consistent with previous experiments conducted in mice and amplify the external validity of these compounds, highlighting their potential as antiseizure remedy candidates. | | 10:02p |
Behavior decoding delineates seizure microfeatures and associated sudden death risks in mice
Behavior and motor manifestations are distinctive yet often overlooked features of epileptic seizures. Seizures can result in transient disruptions in motor control, often organized into specific behavioral patterns that can inform seizure types, onset zones, and outcomes. However, refined analysis of behaviors in epilepsy remains challenging in both clinical and preclinical settings. Current manual video inspection approaches are subjective, time-consuming, and often focus on gross and ambiguous descriptions of seizure behaviors, overlooking much of the intricate behavioral dynamics and action kinematics. Here, we utilized two machine learning-aided tools, DeepLabCut (DLC) and Behavior Segmentation of Open Field in DLC (B-SOiD), to decode previously underexplored behavior and action domains of epilepsy. We identified 63 interpretable behavior groups during seizures in a population of 32 genetically diverse mouse strains. Analysis of these behavior groups demonstrates significant differential behavior expression and complexity that can delineate distinct seizure states, unravel intrinsic seizure progression over time, and inform mouse strain backgrounds and genotypes. We also identified seizure behavior patterns and action/subaction kinematics that determine the risks of sudden unexpected death in epilepsy (SUDEP). These findings underscore the significant potential for translation into inpatient settings for video analysis in epilepsy monitoring units and outpatient settings via home surveillance devices and smartphones. | | 10:02p |
Enhanced proconvulsant sensitivity, not spontaneous rapid swimming activity, is a robust correlate of scn1lab loss-of-function in stable mutant and F0 crispant hypopigmented zebrafish expressing GCaMP6s
Zebrafish models of genetic epilepsy benefit from the ability to assess disease-relevant knock-out alleles with numerous tools, including genetically encoded calcium indicators (GECIs) and hypopigmentation alleles to improve visualization. However, there may be unintended effects of these manipulations on the phenotypes under investigation. There is also debate regarding the use of stable loss-of-function (LoF) alleles in zebrafish, due to genetic compensation (GC). In the present study, we applied a method for combined movement and calcium fluorescence profiling to the study of a zebrafish model of SCN1A, the main gene associated with Dravet syndrome, which encodes the voltage-gated sodium channel alpha1 subunit (Nav1.1). We evaluated for spontaneous and proconvulsant-induced seizure-like activity associated with scn1lab LoF mutations in larval zebrafish expressing a neuronally-driven GECI (elavl3:GCaMP6s) and a nacre mutation causing a common pigmentation defect. In parallel studies of stable scn1labs552 mutants and F0 crispant larvae generated using a CRISPR/Cas9 multi-sgRNA approach, we find that neither stable nor acute F0 larvae recapitulate the previously reported seizure-like rapid swimming phenotype nor does either group show spontaneous calcium events meeting criteria for seizure-like activity based on a logistic classifier trained on movement and fluorescence features of proconvulsant-induced seizures. This constitutes two independent lines of evidence for a suppressive effect against the scn1lab phenotype, possibly due to the GCaMP6s-derived genetic background (AB) or nacre hypopigmentation. In response to the proconvulsant pentylenetetrazole (PTZ), we see evidence of a separate suppressive effect affecting all conspecific larvae derived from the stable scn1labs552 line, independent of genotype, possibly related to a maternal effect of scn1lab LoF in mutant parents or the residual TL background. Nonetheless, both stable and F0 crispant fish show enhanced sensitivity to PTZ relative to conspecific larvae, suggesting that proconvulsant sensitivity provides a more robust readout of scn1lab LoF under our experimental conditions. Our study underscores the unexpected challenges associated with the combination of common zebrafish tools with disease alleles in the phenotyping of zebrafish models of genetic epilepsy. Our work further highlights the advantages of using F0 crispants and the evaluation of proconvulsant sensitivity as complementary approaches that faithfully reflect the shared gene-specific pathophysiology underlying spontaneous seizures in stable mutant lines. Future work to understand the molecular mechanisms by which scn1lab-related seizures and PTZ-related hyperexcitability are suppressed under these conditions may shed light on factors contributing to variability in preclinical models of epilepsy more generally and may identify genetic modifiers relevant to Dravet syndrome. |
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