Biology subjects

Salinas, A.

Publications and source records attributed to Salinas, A..

6 recordsLinked to original sources

bioRxiv2026

A Reproducible Protocol for Embryonic Chicken Dorsal Root Ganglion Explant Culture and Quantitative Neurite Outgrowth Analysis

Background: Primary embryonic dorsal root ganglion (DRG) explants offer an accessible and physiologically relevant organotypic in vitro assay platform that preserves native three-dimensional cellular interactions and supports robust neurite outgrowth, enabling studies of sensory neuron development and neurite outgrowth, as well as controlled assessment of neurotoxicity, and pharmacological compound effects. Methods: Here we provide a comprehensive step-by-step method to micro-dissect and culture embryonic chicken DRGs and quantitatively measure neurite outgrowth. The protocol covers embryo preparation, vertebral column exposure, bilateral DRG microdissection, explant culturing, longitudinal phase-contrast imaging, and neurite image analysis. Results: DRG explants maintained their overall ganglion morphology and remained attached to the culture surface throughout the five-day culture period. Untreated control explants exhibited limited neurite outgrowth, whereas nerve growth factor (NGF) treated explants developed progressively longer and denser radial neurite networks. Neurite outgrowth was readily visualized by live phase contrast microscopy and quantified using an Image-based neurite tracing method, demonstrating the responsiveness of the explant model to NGF and its suitability for quantitative assessment of neurite outgrowth. Conclusion: This simple, low-cost protocol provides an in vitro assay platform for neurotoxicity, neuroregeneration, drug screening, and biomaterial evaluation.

developmental biology↗

bioRxiv2026

External Globus Pallidus Arkypallidal Circuit Dynamics Gate Risk-Taking Behavior

Exploration allows animals to gather information and adapt to changing conditions. Yet, it also exposes them to potential threats, requiring neural systems that weigh uncertainty and regulate behavioral transitions between cautious and exploratory states. These computations are distributed across cortical and subcortical networks, including the basal ganglia, which integrate sensory, motivational, and contextual information to shape action-selection behaviors. Within this circuitry, the globus pallidus externa (GPe) occupies a central but underappreciated role. Once viewed as a relay between striatum and downstream nuclei, the GPe is gaining recognition as a dynamic regulator that integrates diverse inputs and exerts bidirectional control over motor and cognitive processes. Here, we examine arkypallidal NPAS1-expressing GPe (GPeNPAS1) neurons, which form preferential inhibitory projections to the striatal matrix. Chemogenetic manipulations and in vivo calcium measurement reveal that GPeNPAS1 activity modulates and encodes risk-taking behavior sequences, identifying a circuit mechanism by which the GPe can regulate adaptive decision-making in risky contexts.

neuroscience↗

bioRxiv2026

Selective impairment of long-term depression in accumbal D1-MSNs involves calcium-permeable AMPARs in Alzheimer's disease

Alzheimers disease (AD) is increasingly associated with early circuit dysfunction preceding cognitive decline, including neuronal hyperactivity and neuropsychiatric symptoms linked to mesolimbic pathways. The nucleus accumbens (nAc), a central regulator of reward and motivational processing, exhibits early alterations in excitation/inhibition balance in patients and experimental models; however, the synaptic mechanisms underlying this vulnerability remain unclear. Here, we identify a cell-type-specific synaptic mechanism in the nAc linking early intraneuronal A{beta} accumulation to circuit dysfunction. Using a double transgenic APP/PS1 mouse model expressing tdTomato in dopamine D1 receptor-positive medium spiny neurons (D1R+ MSNs), we show that long-term depression (LTD) is selectively impaired in D1R+ MSNs despite comparable A{beta} levels across neuronal subtypes, revealing differential functional vulnerability. This deficit is associated with an increased contribution of calcium-permeable AMPA receptors (CP-AMPARs) and a disruption of mGluR1/5-dependent LTD, a key mechanism regulating AMPAR trafficking. Pharmacological blockade of CP-AMPARs restores synaptic depression, indicating altered receptor composition as a central feature of this phenotype. These synaptic alterations co-occur with reduced dopaminergic signaling and selective behavioral changes characterized by increased consumption of palatable reward and altered baseline context preference, while associative learning remains preserved. Together, these findings reveal a postsynaptic mechanism in which impaired mGluR-dependent plasticity permits persistent CP-AMPAR signaling, shifting synaptic balance toward increased excitatory drive and mesolimbic hyperactivity in AD.

neuroscience↗

bioRxiv2022

Ketone ester-enriched diet ameliorates motor and dopamine release deficits in MitoPark mice

BackgroundParkinsons disease is a progressive, neurodegenerative disease characterized by motor dysfunction and dopamine deficits. The MitoPark mouse recapitulates several facets of Parkinsons disease, including gradual development of motor deficits, which enables the study of potential therapeutic interventions. One therapeutic strategy involves decreasing the mitochondrial metabolic load by inducing ketosis and providing an alternative energy source for neurons, leading to decreased neuronal oxidative stress. ObjectiveWe assessed whether administration of a ketone ester-enriched diet would improve motor and dopamine release deficits in MitoPark mice. MethodsMotor function (rotarod and open field tests), dopamine release (fast-scan cyclic voltammetry), tissue dopamine levels (GC-MS), and dopamine neurons and axons (immunofluorescence) were assessed in MitoPark and control mice fed either the standard or ketone ester-enriched diets. ResultsWhen started on the ketone diet before motor dysfunction onset, MitoPark mice had preserved motor function relative to standard diet MitoPark mice. While the ketone ester enriched diet did not preserve dopamine neurons or striatal dopamine axons, dopamine release in ketone diet MitoPark mice was greater than standard diet MitoPark mice but less than control mice. In a follow up experiment, we began the ketone diet after motor dysfunction onset and observed a modest preservation of motor function in ketone diet MitoPark mice relative to standard diet MitoPark mice. ConclusionThe improvement in motor dysfunction indicates that a ketone ester enriched diet or ketone supplement may represent a promising adjunct treatment for Parkinsons disease.

neuroscience↗

bioRxiv2021

Deficiency in endocannabinoid synthase DAGLB contributes to Parkinson's disease and dopaminergic neuron dysfunction

2-arachidonoyl-glycerol (2-AG), the most abundant endocannabinoid (eCB) in the brain, regulates diverse neural functions. However, whether 2-AG deficiency contributes to Parkinsons disease (PD) and nigral dopaminergic neurons (DANs) dysfunction is unclear. Diacylglycerol lipase and {beta} (DAGLA and DAGLB) mediate the biosynthesis of 2-AG. Using homozygosity mapping and whole-exome sequencing, we linked multiple homozygous loss-of-function mutations in DAGLB to a form of early-onset autosomal recessive PD. We then used RNA sequencing and fiber photometry with genetically encoded eCB sensors to demonstrate that DAGLB is the main 2-AG synthase in nigral DANs. Genetic knockdown of Daglb by CRISPR/Cas9 in mouse nigral DANs substantially reduces 2-AG levels in the substantia nigra (SN). The SN 2-AG levels are markedly correlated with the vigor of movement during the acquisition of motor skills, while Daglb-deficiency impairs motor learning. Conversely, pharmacological enhancement of 2-AG levels increases nigral DAN activity and dopamine release and improves motor learning. Together, we demonstrate that DAGLB-deficiency contributes to the etiopathogenesis of PD, reveal the importance of DAGLB-mediated 2-AG biosynthesis in nigral DANs in regulating neural activity and dopamine release, and provide preclinical evidence for the beneficial effects of 2-AG augmentation in PD treatment.

neuroscience↗

bioRxiv2020

Reproductive resilience but not root architecture underpin yield improvement in maize

Plants capture soil resources to produce the grains required to feed a growing population. Because plants capture water and nutrients through roots, it was proposed that changes in root systems architecture (RSA) underpin the three-fold increase in maize grain yield over the last century1,2,3,4. Within this framework, improvements in reproductive resilience due to selection are caused by increased water capture1. Here we show that both root architecture and yield have changed with decades of maize breeding, but not the water capture. Consistent with Darwinian agriculture5 theory, improved reproductive resilience6,7 enabled farmers increase the number of plants per unit land8,9,10, capture soil resources, and produced more dry matter and grain. Throughout the last century, selection operated to adapt roots to crowding, enabling reallocation of C from large root systems to the growing ear and the small roots of plants cultivated in high plant populations in modern agriculture.

plant biology↗