Biology subjects

Parro, C.

Publications and source records attributed to Parro, C..

4 recordsLinked to original sources

bioRxiv2025

Combined CSF1R Inhibition and Sensory Gamma Stimulation Provide Protective Effects in a Mouse Model of Alzheimers Disease

The CSF1R inhibitor PLX3397, an FDA-approved treatment for a rare cancer, has been shown to reduce microglia count, lower inflammation, and increase synaptic markers in mouse models of Alzheimers disease (AD). However, the effects of PLX3397 on neural function in AD remain largely unknown. Here, we characterized the effects of PLX3397 treatment in 5xFAD mice. While PLX3397 increased synaptic density, it reduced the percentage of neurons phase-locked to gamma oscillations. This neural decoupling was closely associated with gene expression changes related to synapse organization. We investigated whether Gamma ENtrainment Using Sensory (GENUS) stimulation could counterbalance the neural circuit alterations induced by PLX3397. GENUS + PLX3397 restored gamma phase-locking, reshaped gene expression signatures, and improved learning and memory better than either treatment alone in 5xFAD mice. These findings suggest that CSF1R inhibitors like PLX3397 may benefit from a multimodal approach combining microglial targeting with non-invasive sensory stimulation to support neural physiology and improve cognitive function in AD.

neuroscience↗

bioRxiv2021

A multisensory circuit for gating intense aversive experiences

The ventral hippocampus (vHPC) is critical for both learned and innate fear, but how discrete projections control different types of fear is poorly understood. Here, we report a novel excitatory circuit from a subpopulation of the ventral hippocampus CA1 subfield (vCA1) to the inhibitory peri-paraventricular nucleus of the hypothalamus (pPVN) which then routes to the periaqueductal grey (PAG). We find that vCA1[->]pPVN projections modulate both learned and innate fear. Fiber photometric calcium recordings reveal that activity in vCA1[->]pPVN projections increases during the first moments of exposure to an unconditioned threat. Chemogenetic or optogenetic silencing of vCA1[->]pPVN cell bodies or vCA1[->]pPVN axon terminals in the pPVN enhances the initial magnitude of both active and passive unconditioned defensive responses, irrespective of the sensory modalities engaged by a particular innate threat. Moreover, silencing produces a dramatic impact on learned fear without affecting milder anxiety-like behaviors. We also show that vCA1[->]pPVN projections monosynaptically route to the PAG, a key brain region that orchestrates the fear response. Surprisingly, optogenetic silencing of vCA1 terminals in the pPVN titrates the level of c-Fos neural activity in the PAG differently for learned versus innate threats. Together, our results show how a novel vCA1[->]pPVN circuit modulates neuronal activity in the PAG to regulate both learned and innate fear. These findings have implications for how initial trauma processing may influence maladaptive defensive behaviors across fear and trauma-related disorders. One Sentence SummaryA multisensory gate for high intensity aversive experiences.

neuroscience↗

bioRxiv2020

The low complexity motif of cytoplasmic polyadenylation element binding protein 3 (CPEB3) is critical for the trafficking of its targets in neurons

Biomolecular condensates, membraneless organelles found throughout the cell, play critical roles in many aspects of cellular function. Ribonucleoprotein granules (RNPs), a type of biomolecular condensate found in neurons that are necessary for local protein synthesis and are involved in long-term potentiation (LTP). Several RNA-binding proteins present in RNPs are necessary for the synaptic plasticity involved in LTP and long-term memory. Most of these proteins possess low complexity motifs, allowing for increased promiscuity. We explore the role the low complexity motif plays for RNA binding protein cytoplasmic polyadenylation element binding protein 3 (CPEB3), a protein necessary for long-term memory persistence. We found that RNA binding and SUMOylation are necessary for CPEB3 localization to the P body, thereby having functional implications on translation. Here, we investigate the role of the low complexity motif of CPEB3 and find that it is necessary for P body localization and downstream targeting for local protein synthesis.

neuroscience↗

bioRxiv2017

The Neural Basis of Motivational Influences on Cognitive Control: An ALE Meta-Analysis

Cognitive control mechanisms support the deliberate regulation of thought and behavior based on current goals. Recent work suggests that motivational incentives improve cognitive control, and has begun to elucidate the brain regions that may support this effect. Here, we conducted a quantitative meta-analysis of neuroimaging studies of motivated cognitive control using activation likelihood estimation (ALE) and Neurosynth in order to delineate the brain regions that are consistently activated across studies. The analysis included functional neuroimaging studies that investigated changes in brain activation during cognitive control tasks when reward incentives were present versus absent. The ALE analysis revealed consistent recruitment in regions associated with the frontoparietal control network including the inferior frontal sulcus (IFS) and intraparietal sulcus (IPS), as well as consistent recruitment in regions associated with the salience network including the anterior insula and anterior mid-cingulate cortex (aMCC). A large-scale exploratory meta-analysis using Neurosynth replicated the ALE results, and also identified the caudate nucleus, nucleus accumbens, medial thalamus, inferior frontal junction/premotor cortex (IFJ/PMC), and hippocampus. Finally, we conducted separate ALE analyses to compare recruitment during cue and target periods, which tap into proactive engagement of rule-outcome associations, and the mobilization of appropriate viscero-motor states to execute a response, respectively. We found that largely distinct sets of brain regions are recruited during cue and target periods. Altogether, these findings suggest that flexible interactions between frontoparietal, salience, and dopaminergic midbrain-striatal networks may allow control demands to be precisely tailored based on expected value.

neuroscience↗