Biology subjects

Hernandez, C. M.

Publications and source records attributed to Hernandez, C. M..

12 recordsLinked to original sources

bioRxiv2025

Optogenetic inhibition reveals distinct contributions of medial prefrontal cortex to intertemporal choice in young and aged rats

The ability to choose adaptively between rewards differing in magnitude and delay (intertemporal choice) is critical for numerous life outcomes. Compared to younger adults, older adults tend to exhibit greater preference for large, delayed over small, immediate rewards (i.e., less delay discounting), which could lead to missed opportunities to obtain resources necessary for quality of life. Intertemporal choice is mediated by the prefrontal cortex, but how this is impacted by advanced age is not well understood. We used optogenetic inactivation to investigate contributions of medial prefrontal cortex (mPFC) during distinct components of an intertemporal choice task in young and aged rats. mPFC inactivation during deliberation (during decisions between small, immediate vs. large, delayed rewards) increased preference for large, delayed rewards in both age groups. In contrast, inactivation during delays prior to large reward delivery increased preference for large, delayed rewards only in aged rats. Choices were unaffected by inactivation during other task phases. Results suggest that mPFC integrates information regarding anticipated outcomes into the decision process across the whole lifespan, but that only in aging is mPFC critical for consolidating information regarding reward delays into the decision structure in order to modulate choice behavior.

neuroscience↗

bioRxiv2025

Current estimates of population resilience do not predict resilience to directional environmental shifts

Natural systems worldwide are exposed to gradual changes imposed by directional environmental shifts, known as ramp disturbances. However, contemporary assessments of population resilience focus on the resistance and recovery of systems following one-off (i.e., pulse) disturbances. Thus, our current perception of demographic resilience overlooks the potential impacts of the cumulative effects of ramp disturbances on population dynamics. Simulating 50-year ramp disturbance scenarios upon the survival and fecundity dynamics of 511 populations across 344 species, we illustrate non-linear patterns in how directional environmental shifts will reshape the resilience of natural populations. Accordingly, existing estimates of population resilience are not robust against a backdrop of ongoing and continuous environmental change. Instead, we demonstrate the need to quantify how the relative partitioning of energetic resources across survival vs. fecundity informs population resilience. Our findings challenge the use of well-established approaches in forecasting population resilience to ongoing global change.

ecology↗

bioRxiv2024

Development and Characterization of 50 nanometer diameter Genetically Encoded Multimeric Nanoparticles

The mechanisms that regulate the physical properties of the cell interior remain poorly understood, especially at the mesoscale. Many crucial macromolecules and molecular assemblies such as ribosomes, RNA polymerase, and biomolecular condensates span the mesoscale size range, and changes in mesoscale physical properties have been suggested to be crucial for both normal physiology and disease. Therefore, we need better tools to study the cellular environment at this scale. Physical properties of the cell can be inferred through analysis of the motion of tracer nanoparticles, an approach called nanorheology. This requires the introduction of nanoparticles to cells, which can be labor intensive and slow. Genetically Encoded Multimeric nanoparticles (GEMs) were recently developed to address this limitation. GEMs consist of scaffold proteins fused to fluorescent tags that self-assemble into bright and stable nanoparticles of defined geometry. However, extremely sensitive microscopes were required to track previous (40nm-GEMs). Here, we describe the development and characterization of 50 nm diameter GEMs (50nm-GEMs) that are brighter and probe a slightly longer length scale. 50nm-GEMs will make high-throughput nanorheology accessible to a broader range of researchers and reveal new insights into the biophysical properties of cells.

biophysics↗

bioRxiv2023

A modular chemigenetic calcium indicator enables in vivo functional imaging with near-infrared light

Genetically encoded fluorescent calcium indicators have revolutionized neuroscience and other biological fields by allowing cellular-resolution recording of physiology during behavior. However, we currently lack bright, genetically targetable indicators in the near infrared that can be used in animals. Here, we describe WHaloCaMP, a modular chemigenetic calcium indicator built from bright dye-ligands and protein sensor domains that can be genetically targeted to specific cell populations. Fluorescence change in WHaloCaMP results from reversible quenching of the bound dye via a strategically placed tryptophan. WHaloCaMP is compatible with rhodamine dye-ligands that fluoresce from green to near-infrared, including several dye-ligands that efficiently label the central nervous system in animals. When bound to a near-infrared dye-ligand, WHaloCaMP1a is more than twice as bright as jGCaMP8s, and shows a 7x increase in fluorescence intensity and a 2.1 ns increase in fluorescence lifetime upon calcium binding. We use WHaloCaMP1a with near-infrared fluorescence emission to image Ca2+ responses in flies and mice, to perform three-color multiplexed functional imaging of hundreds of neurons and astrocytes in zebrafish larvae, and to quantitate calcium concentration using fluorescence lifetime imaging microscopy (FLIM).

neuroscience↗

bioRxiv2023

A standard protocol to report discrete stage-structured demographic information

O_LIStage-based demographic methods, such as matrix population models (MPMs), are powerful tools used to address a broad range of fundamental questions in ecology, evolutionary biology, and conservation science. Accordingly, MPMs now exist for over 3,000 species worldwide. These data are being digitised as an ongoing process and periodically released into two large open-access online repositories: the COMPADRE Plant Matrix Database and the COMADRE Animal Matrix Database. During the last decade, data archiving and curation of COMPADRE and COMADRE, and subsequent comparative research, have revealed pronounced variation in how MPMs are parameterized and reported. C_LIO_LIHere, we summarise current issues related to the parameterisation and reporting of MPMs that arise most frequently and outline how they affect MPM construction, analysis, and interpretation. To quantify variation in how MPMs are reported, we present results from a survey identifying key aspects of MPMs that are frequently unreported in manuscripts. We then screen COMPADRE and COMADRE to quantify how often key pieces of information are omitted from manuscripts using MPMs. C_LIO_LIOver 80% of surveyed researchers (n=60) state a clear benefit to adopting more standardised methodologies for reporting MPMs. Furthermore, over 85% of the 300 MPMs assessed from COMPADRE and COMADRE omitted one or more elements that are key to their accurate interpretation. Based on these insights, we identify fundamental issues that can arise from MPM construction and communication and provide suggestions to improve clarity, reproducibility, and future research utilising MPMs and their required metadata. To fortify reproducibility and empower researchers to take full advantage of their demographic data, we introduce a standardized protocol to present MPMs in publications. This standard is linked to www.compadre-db.org, so that authors wishing to archive their MPMs can do so prior to submission of publications, following examples from other open-access repositories such as DRYAD, Figshare, and Zenodo. C_LIO_LICombining and standardising MPMs parameterized from populations around the globe and across the tree of life opens up powerful research opportunities in evolutionary biology, ecology, and conservation research. However, this potential can only be fully realised by adopting standardised methods to ensure reproducibility. C_LI

ecology↗

bioRxiv2022

Impairments in fear extinction memory and basolateral amygdala plasticity in the TgF344-AD rat model of Alzheimer's disease are distinct from non-pathological aging.

Fear-based disorders such as posttraumatic stress disorder (PTSD) steepen age-related cognitive decline and doubles the risk for developing Alzheimers disease. Due to the seemingly hyperactive properties of fear memories, PTSD symptoms can worsen with age. Perturbations in the synaptic circuitry supporting fear memory extinction are key neural substrates of PTSD. The basolateral amygdala (BLA) is a medial temporal lobe structure critical in the encoding, consolidation, and retrieval of fear memories. As little is known about fear extinction memory and BLA synaptic dysfunction within the context of aging and AD, the goal of this study was to investigate how fear extinction memory deficits and basal amygdaloid nucleus (BA) synaptic dysfunction differentially associate in non-pathological aging and AD in the TgF344AD (TgAD) rat model of AD. Young, middle-aged, and older-aged WT and TgAD rats were trained on a delay fear conditioning and extinction procedure prior to ex vivo extracellular field potential recording experiments in the BA. Relative to young WT rats, long-term extinction memory was impaired, and in general, associated with a hyperexcitable BA and impaired LTP in TgAD rats at all ages. In contrast, long-term extinction memory was impaired in aged WT rats and associated with impaired LTP but not BA hyperexcitability. Interestingly, the middle-aged TgAD rats showed intact short-term extinction and BA LTP, suggestive of a compensatory mechanism, whereas differential neural recruitment in older-aged WT rats may have facilitated short-term extinction. As such, associations between fear extinction memory and amygdala deficits in non-pathological aging and AD are dissociable. SignificanceAdults with fear-based disorders like post-traumatic stress disorder are at an increased risk for developing age-related cognitive decline and Alzheimers disease (AD). Moreover, negative emotional affect is an early marker of AD. The link between fear-based disorders and AD creates a disadvantage for achieving positive outcomes later in life. Central to the circuitry underlying fear disorders are medial temporal lobe structures like the basal amygdaloid nucleus (BA). However, the role of the BA in fear-based disorders exacerbated by aging and AD is not well understood. Using the TgF344AD rat model of AD, we investigated how fear extinction memory impairments and BA synaptic function are impacted by aging and AD and whether these processes differentially associate in non-pathological aging and AD.

neuroscience↗

bioRxiv2022

Profiling the plasmid conjugation potential of urinary E. coli

Escherichia coli is often associated with urinary tract infection (UTI). Antibiotic resistance in E. coli is an ongoing challenge in managing UTI. Extrachromosomal elements - plasmids - are vectors for clinically relevant traits, such as antibiotic resistance, with conjugation being one of the main methods for horizontal propagation of plasmids in bacterial populations. Targeting of conjugation components has been proposed as a strategy to curb spread of plasmid-borne antibiotic resistance. Understanding the types of conjugative systems present in urinary E. coli isolates is fundamental to assessing the viability of these strategies. In this study, we profile the two well studied conjugation systems (F-type and P-type) in the draft genomes of 65 urinary isolates of E. coli obtained from bladder urine of adult women with and without UTI-like symptoms. Most of these isolates contained plasmids and we found that conjugation genes are abundant/ubiquitous, diverse, and often associated with IncF plasmids. To validate conjugation of these urinary plasmids, we conjugated the plasmids from two urinary isolates, UMB1223 (predicted to have F-type genes) and UMB1284 (predicted to have P-type genes), into the K-12 E. coli strain MG1655. Overall, the findings of this study support the notion that care should be taken in targeting any individual component of a urinary E. coli isolates conjugation system, given the inherent mechanistic redundancy, gene diversity, and different types of conjugation systems in this population.

microbiology↗

bioRxiv2019

Maternal Effect Senescence and Fitness: A Demographic Analysis of a Novel Model Organism

Maternal effect senescence--a decline in offspring fitness with maternal age--has been demonstrated in a range of taxa, including humans. Despite decades of phenotypic studies, it remains unclear how maternal effect senescence impacts population structure or evolutionary fitness. To understand the impact of maternal effect senescence on population dynamics, fitness, and selection, we used data from individual-based culture experiments on the microscopic aquatic invertebrate, Brachionus manjavacas (Rotifera), to develop a series of matrix population models in which individuals are classified jointly by age and maternal age. By comparing the results derived from models with and without maternal effects, we found that the fitness difference due to maternal effect senescence arises primarily through decreased fertility, particularly at maternal ages corresponding to the peak reproductive output. In all models, selection gradients decrease with increasing age. They also decrease with maternal age for large maternal ages, implying that maternal effect senescence can evolve through the same process as in Hamiltons theory of the evolution of demographic senescence. We find that maternal effect senescence significantly alters population structure and fitness for B. manjavacas, a species with high maternal investment and maximum reproduction in early-to mid-life. The models developed here were built with data from an emerging model organism, and are widely applicable to evaluate the fitness consequences of maternal effect senescence across species with diverse aging and fertility schedule phenotypes.

evolutionary biology↗

bioRxiv2019

Age and ketogenic diet have dissociable effects on synapse-related gene expression between hippocampal subregions

As the number of individuals living beyond the age of 65 is rapidly increasing, so is the need to develop strategies to combat the age-related cognitive decline that may threaten independent living. Although the link between altered neuronal signaling and age-related cognitive impairments is not completely understood, it is evident that declining cognitive abilities are at least partially due to synaptic dysfunction. Aging is accompanied by well-documented changes in both excitatory and inhibitory synaptic signaling across species. Age-related synaptic alterations are not uniform across the brain, however, with different regions showing unique patterns of vulnerability in advanced age. In the hippocampus, increased activity within the CA3 subregion has been observed across species, and this can be reversed with anti-epileptic medication (Bakker et al., 2012). In contrast to CA3, the dentate gyrus shows reduced activity with age and declining metabolic activity. Ketogenic diets have been shown to decrease seizure incidence and severity in epilepsy, improve metabolic function in diabetes type II, and improve cognitive function in aged rats. This link between neuronal activity and metabolism suggests that metabolic interventions may be able to ameliorate synaptic signaling deficits accompanying advanced age. We therefore investigated the ability of a dietary regimen capable of inducing nutritional ketosis and improving cognition to alter synapse-related gene expression across the dentate gyrus, CA3 and CA1 subregions of the hippocampus. Following 12 weeks of a ketogenic or calorie-matched standard diet, RTq-PCR was used to quantify expression levels of excitatory and inhibitory synaptic signaling genes within CA1, CA3 and dentate gyrus. While there were no age or diet-related changes in CA1 gene expression, expression levels were significantly altered within CA3 by age and within the dentate gyrus by diet for several genes involved in presynaptic glutamate regulation and postsynaptic excitation and plasticity. These data demonstrate subregion-specific alterations in synaptic signaling with age and the potential for a ketogenic diet to alter these processes in dissociable ways across different brain structures that are uniquely vulnerable in older animals.

neuroscience↗

bioRxiv2019

Aging alters the role of basolateral amygdala in intertemporal choice

Aging is associated with an increased ability to delay gratification. Moreover, even when matched for performance, young and aged subjects recruit distinct brain circuitry to complete complex cognitive tasks. Experiments herein used an optogenetic approach to test whether altered recruitment of the basolateral amygdala (BLA), a brain region implicated in valuation of reward-cost contingencies, contributes to age-dependent changes in intertemporal decision making. BLA inactivation while rats deliberated prior to choices between options that yielded either small, immediate or large, delayed rewards rendered both young and aged rats less impulsive. In contrast, BLA inactivation after choices were made (during evaluation of choice outcomes) rendered young rats more impulsive but had no effect in aged rats. These data define multiple, temporally-discrete roles for BLA circuits in intertemporal decision making and implicate altered recruitment of BLA in the elevated preference for delayed rewards that is characteristic of advanced age. Impact StatementBasolateral amygdala (BLA) performs multiple, temporally-discrete functions during intertemporal decision making. Differential engagement of BLA contributes to the enhanced ability to delay gratification that is characteristic of advanced ages.

neuroscience↗

bioRxiv2017

Optogenetic inhibition reveals distinct roles for basolateral amygdala activity at discrete timepoints during risky decision making

Decision making is a multifaceted process, consisting of several distinct phases that likely require different cognitive operations. Previous work showed that the basolateral amygdala (BLA) is a critical substrate for decision making involving risk of punishment; however, it is unclear how the BLA is recruited at different stages of the decision process. To this end, the current study used optogenetics to inhibit the BLA during specific task phases in a model of risky decision making (Risky Decision-making Task; RDT) in which rats choose between a small, \"safe\" reward and a large reward accompanied by varying probabilities of footshock punishment. Rats received intra-BLA microinjections of viral vectors carrying either halorhodopsin (eNpHR3.0-mCherry) or mCherry alone (control) followed by optic fiber implants and were trained in the RDT. Laser stimulation during the task occurred during either intertrial interval, deliberation, or reward outcome phases, the latter of which was further divided into the three possible outcomes (small, safe; large, unpunished; large, punished). Inhibition of the BLA selectively during the deliberation phase decreased choice of the large, risky outcome (decreased risky choice). In contrast, BLA inhibition selectively during delivery of the large, punished outcome increased risky choice. Inhibition had no effect during the other phases, nor did it affect performance in control rats. Collectively, these data indicate that the BLA can either inhibit or promote choice of risky options, depending on the phase of the decision process in which it is active.\n\nSignificance StatementTo date, most behavioral neuroscience research on neural mechanisms of decision making has employed techniques that preclude assessment of distinct phases of the decision process. Here we show that optogenetic inhibition of the basolateral amygdala (BLA) has opposite effects on choice behavior in a rat model of risky decision making depending on the phase in which inhibition occurs. BLA inhibition during a period of deliberation between small, safe and large, risky outcomes decreased risky choice. In contrast, BLA inhibition during receipt of the large, punished outcome increased risky choice. These findings highlight the importance of temporally targeted approaches to understand neural substrates underlying complex cognitive processes. More importantly, they reveal novel information about dynamic BLA modulation of risky choice.

neuroscience↗

bioRxiv2017

The Anti-Epileptic Ketogenic Diet Alters Hippocampal Transporter Levels and Reduces Adiposity in Aged Rats

Nutritional ketosis is induced by high fat/low carbohydrate dietary regimens, which produce high levels of circulating ketone bodies, shifting metabolism away from glucose utilization. While ketogenic diets (KD) were initially introduced to suppress seizures, they are garnering attention for their potential to treat a myriad of neurodegenerative and metabolic disorders that are associated with advanced age. The feasibility and physiological impact of implementing a long-term KD in old animals, however, has not been systematically examined. In this study, young and aged rats consumed a calorically- and nutritionally-matched KD or control diet for 12 weeks. All KD-fed rats maintained higher levels of {beta}-hydroxybutyrate (BHB) and lower levels of glucose relative to controls. However, it took the aged rats longer to reach asymptotic levels of BHB compared to young animals. Moreover, KD-fed rats had significantly less visceral white and brown adipose tissue than controls without a loss of lean mass. Interestingly, the KD lead to significant alterations in protein levels of hippocampal transporters for monocarboxylates, glucose and vesicular glutamate and GABA. Most notably, the age-related decline in vesicular glutamate transporter expression was reversed by the KD. These data demonstrate the feasibility and potential benefits of KDs for treating age-associated neural dysfunction.

neuroscience↗