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Llano, D.

Publications and source records attributed to Llano, D..

3 recordsLinked to original sources

Reduced MOV10 reveals novel functional cortical connections in an increased fear response

The RNA helicase MOV10 is highly expressed in developing brain, is present in synapses and is required for embryonic viability. A murine brain-specific knockout of MOV10 (Mov10 Deletion) has a thickened cortex, abnormal dendritic arborization and enhanced fear memory. In human studies, MOV10 is among the loci that is correlated with enhanced cortical brain volumes and is also significantly associated with substance dependence by epigenetic profiling. Here we demonstrate that Mov10 Deletion mice show enhanced fear learning that is aligned with impaired structural connectivity of canonical fear circuits revealed by Diffusion Tensor Imaging. We propose a model where MOV10 loss leads to increased GABRA2 expression in the hippocampus and reduced anatomical connectivity that drives augmented fear learning. Memory reactivation is observable during fear memory retrieval as an overall increase in fMRI functional activity in cortical regions. Taken together, this framework identifies that enhanced fear in the MOV10 model is driven via a "corticalized" fear response during re-exposure to the training context that is not driven by the canonical fear circuit. These findings support a molecular basis for non-traditional enhanced learning mechanisms activated by fearful events that shed light on the intractability of fear memories with the potential to inform PTSD and substance dependence disorders.

neuroscience↗

Disrupted white matter microstructure in chronic Zika virus-infected adults

Systemic viral infections with neurotropic potential pose significant global health challenges. The Zika virus (ZIKV) is known for its pronounced neurotropism, with recent infectious clusters raising renewed public health concerns. While research has predominantly focused on congenital populations, growing evidence suggests that the mature central nervous system (CNS) is also vulnerable. However, no study has examined the long-term impact of ZIKV infection on the adult human brain. To address this gap, we studied a rare group of adult ZIKV patients presenting with both peripheral (Guillain-Barre Syndrome; GBS) and CNS-related neurological symptoms. We compared these patients at the chronic stage (5 to 12 months post-infection) to healthy controls and to patients with GBS of non-ZIKV etiology (total N=43). Structural and functional measures included cortical thickness, white matter hyperintensities, diffusion metrics, and resting-state functional connectivity. Despite the rarity of both patient populations, power analyses indicated that our sample size could detect large group differences--effect sizes deemed reasonable given the severity of neurological symptoms in the ZIKV group. Nonetheless, our multimodal analyses yielded null results, with Bayesian statistics (where applicable) providing evidence for a lack of effects. The null findings suggest that chronic ZIKV infection in adults is not associated with brain changes of large magnitude. Importantly, this study offers detailed clinical characterization of a heavily understudied group. In light of recent ZIKV outbreaks, this characterization underscores the need to monitor, study, and provide longitudinal care to adult survivors of severe ZIKV infections.

neuroscience↗

V-NeuroStack: 3D Time Stacks for Identifying Patterns in Calcium Imaging Data

BackgroundUnderstanding functional correlations between the activities of neuron populations is vital for the analysis of neuronal networks. Analyzing large-scale neuroimaging data obtained from hundreds of neurons simultaneously poses significant visualization challenges. We developed V-NeuroStack, a novel network visualization tool to visualize data obtained using calcium imaging of spontaneous activity of cortical neurons in a mouse brain slice. New MethodV-NeuroStack creates 3D time stacks by stacking 2D time frames for a period of 600 seconds. It provides a web interface that enables exploration and analysis of data using a combination of 3D and 2D visualization techniques. Comparison with existing MethodsPrevious attempts to analyze such data have been limited by the tools available to visualize large numbers of correlated activity traces. V-NeuroStack can scale data sets with at least a few thousand temporal snapshots. ResultsV-NeuroStacks 3D view is used to explore patterns in the dynamic large-scale correlations between neurons over time. The 2D view is used to examine any timestep of interest in greater detail. Furthermore, a dual-line graph provides the ability to explore the raw and first-derivative values of a single neuron or a functional cluster of neurons. ConclusionsV-NeuroStack enables easy exploration and analysis of large spatio-temporal datasets using two visualization paradigms: (a) Space-Time cube (b)Two-dimensional networks, via web interface. It will support future advancements in in vitro and in vivo data capturing techniques and can bring forth novel hypotheses by permitting unambiguous visualization of large-scale patterns in the neuronal activity data.

neuroscience↗