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Gutierrez, R.

Publications and source records attributed to Gutierrez, R..

At least 19 recordsLinked to original sources
bioRxiv2026

RNA Polymerase III subunit Polr3a is required for craniofacial cartilage and bone development

Transcription by RNA Polymerase III (Pol III) is essential for ribosome biogenesis and translation in all cells, but pathogenic variants in genes encoding subunits of Pol III lead to tissue-specific phenotypes including craniofacial differences. To understand the function of Pol III in craniofacial development, we examined polr3a mutant zebrafish. These mutants display hypoplasia of the neural crest cell-derived craniofacial cartilage and bone but, surprisingly, no significant changes were observed in neural crest cell proliferation or survival during embryogenesis. At larval stages, increased cell death was observed throughout the head, including in the craniofacial cartilage. These changes coincide with reduced transcription of transfer RNAs and reduced ribosome biogenesis in polr3a mutant zebrafish. To determine tissue-specific transcriptional changes, we performed single-cell RNA-sequencing. Analysis revealed both global and cartilage-specific changes, including upregulation of tp53. However, Tp53 inhibition alone was not sufficient to rescue craniofacial cartilage and bone, indicating that additional factors are important to support cartilage and bone growth in polr3a mutants. Altogether, our study provides new mechanistic insights into the functions of Pol III in craniofacial development. Author SummaryCraniofacial anomalies account for around 33% of all congenital birth defects and many of these are associated with defects in neural crest cell development. Disruptions in RNA Polymerase III, which plays important roles in ribosome biogenesis and translation, can result in tissue-specific phenotypes including craniofacial anomalies. However, the mechanisms underlying these craniofacial anomalies are not well understood. Here, we establish a zebrafish model to understand how a mutation in Pol III subunit polr3a affects craniofacial development. We observe hypoplasia of the craniofacial cartilage and bone in polr3a mutant zebrafish along with diminished transcription of transfer RNAs and reduced ribosome biogenesis. This leads to reduced proliferation and increased cell death throughout the head, but we do not detect any differences in early neural crest cell development. Using single-cell RNA-sequencing, we examine the transcriptional changes both broadly throughout the head and specifically within the craniofacial cartilage and identify upregulation of the Tp53 pathway. Inhibition of tp53 only partially rescues cartilage and bone development, suggesting that Tp53-independent mechanisms contribute to cranioskeletal development in polr3a mutant zebrafish. Altogether, these studies highlight the critical function of Pol III during development and specifically in the differentiation and growth of craniofacial cartilage and bone.

developmental biology↗
bioRxiv2025

Different data analysis models for detecting miRNAs using nanopores

Nanopore sensors offer exceptional sensitivity for detecting single molecules, making them ideal for early disease diagnostics. In this study, we present a multiplexed nanopore-based assay that combines DNA-barcoded probes with advanced computational analysis to detect microRNAs (miRNAs) with high specificity and quantitative accuracy. Each probe binds selectively to its target biomarker and generates a characteristic delay in the ionic current signal upon translocation through the nanopore, enabling label-free detection. We evaluated three analytical strategies for classifying delayed versus non-delayed events: (1) moving standard deviation (MSD), (2) spectral entropy (SE), and (3) a convolutional neural network (CNN). While MSD and SE rely on manually defined thresholds and exhibit limited sensitivity, the CNN model, trained on image representations of raw current traces, achieved near-perfect classification performance across all metrics. Grad-CAM visualisation confirmed that the CNN focused on biophysically relevant signal regions, enhancing interpretability and generalisability. All methods produced sigmoidal concentration-response curves consistent with expected binding kinetics, and nanopore-derived delay metrics closely matched RT-qPCR validation data. All three methods were capable of distinguishing between signal classes; however, the CNN model demonstrated superior sensitivity and robustness. This work highlights the importance of data interpretation in nanopore sensing and presents a comparative framework for binary event classification. The findings pave the way for the development of machine learning-driven nanopore diagnostics capable of detecting diverse biomarker types at the single-molecule level.

biophysics↗
bioRxiv2025

Enduring Autism-like Phenotypes and Deregulated Hypothalamic Prosocial Peptides After Early-Life Exposure to Indoor Flame Retardants in Male C57BL/6 Mice

BackgroundPolybrominated diphenyl ethers (PBDEs) are neuroendocrine disrupting chemicals that produce adverse neurodevelopmental effects. PBDEs have been implicated as risk factors for autism spectrum disorder (ASD), which is characterized by abnormal psychosocial functioning and is commonly accompanied by co-morbidities such as cognitive and attentional deficits. Here, we used a mouse model with translationally relevant exposure to establish direct causal evidence that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in male offspring. MethodsC57Bl6/N mouse dams were exposed to a commercial PBDE mixture, DE-71, via oral administration of 0 (vehicle control, VEH/CON), 0.1 (L-DE-71), or 0.4 (H-DE-71) mg/kg bw/d for 10 weeks, spanning three weeks prior to gestation through the end of lactation at postnatal day (PND) 21. ResultsMass spectrometric analysis indicated dose-dependent transfer of PBDEs (in ppb) to brains of F1 male offspring at PND 30, with reduction in levels by PND 110. Adult F1 male offspring displayed ASD-relevant neurobehavioral phenotypes, including impaired short- and long-term social recognition memory (SRM), despite intact general sociability, and exaggerated repetitive behavior. Exposed mice also displayed altered olfactory discrimination of social odors, impaired novel object recognition memory, and reduced open field habituation. However, no changes were observed in anxiety-like, sensorimotor, or depressive-like behaviors relative to VEH/CON. At the molecular level, DE-71 exposed males displayed deregulated gene markers of prosocial neuropeptides. Oxt was upregulated in the paraventricular nucleus (PVN); Avp was upregulated in the PVN and bed nucleus of the stria terminalis (BNST) but downregulated in the lateral septum (LS); Avp1ar and Adcyap1 were upregulated in the BNST; and Adcyap1r1 was upregulated in the PVN, supraoptic nucleus (SON), and BNST. ConclusionsThese findings demonstrate that developmental PBDE exposure produces enduring behavioral and neurochemical phenotypes that resemble core domains of ASD, which may result from early neurodevelopmental reprogramming within central social and memory networks.

neuroscience↗
bioRxiv2025

The Crunchometer: A Low-Cost, Open-Source Acoustic Analysis of Feeding Microstructure

Elucidating the neuronal circuits that govern appetite requires precise, high-resolution monitoring of the microstructure of solid food consumption, a need unmet by existing tools, which are either costly or lack the temporal resolution to align feeding events with neuronal activity. To overcome this, we developed the Crunchometer, a low-cost, open-source acoustic system that uses computational algorithms to generate high-resolution feeding ethograms from the sounds produced during solid food consumption. Validation across energy states (hunger/satiety) confirmed its sensitivity to changes in feeding microstructure, and the system reliably detected semaglutide-induced suppression of intake and reduced preference for a high-fat diet. Leveraging its seamless integration with in vivo recordings in freely behaving mice, we paired the Crunchometer with lateral hypothalamus (LH) electrophysiology to identify "meal-related" neurons that track entire meals rather than individual bouts. Calcium imaging further revealed that distinct subsets of LH GABAergic and glutamatergic neurons were tuned to feeding only, to licking only, or to both behaviors. Thus, LH neuronal ensembles differentially encode the consumption of solid food versus liquid sucrose. These findings demonstrate that the Crunchometer is a robust, accessible platform for dissecting the neural correlates of feeding behavior at the resolution of a single bite. Significance statementThe Crunchometer is a low-cost, open-source technology that democratizes feeding analysis, enabling the precise dissection of neuronal circuits involved in appetite to advance therapies for obesity and eating disorders.

neuroscience↗
bioRxiv2025

Sex-specific effects of appetite suppressants and stereotypy in rats

This study investigated the sex-specific effects of commonly prescribed appetite suppressants on body weight and the manifestation of motor side effects, specifically stereotypy. Employing video recordings and DeepLabCut (DLC) for precise behavioral quantification, we analyzed stereotypy, defined as purposeless, repetitive motor behaviors, in male and female rats. Under control (saline) conditions, male rats exhibited a greater propensity for weight gain compared to females. However, in contrast, female rats demonstrated greater and more homogenous weight loss than males following the administration of diethylpropion and tesofensine. Phentermine and mazindol induced comparable weight loss in both sexes, whereas cathine elicited weight reduction exclusively in males. 5-HTP and d-amphetamine administration only prevented weight gain relative to controls. Analysis of motor side effects revealed that drugs primarily targeting dopamine pathways - specifically, phentermine, mazindol, diethylpropion, cathine, and d-amphetamine - induced pronounced stereotypies, particularly head-weaving, in both sexes. Interestingly, tesofensine elicited head-weaving behavior exclusively in female subjects, albeit to a lesser extent than that observed with other dopaminergic agents; conversely, tesofensine was most frequently associated with orolingual dyskinesia. Moreover, one of the most potent forms of stereotypy--backward locomotion, here referred to as "moonwalking"--was sporadically observed only following the administration of phentermine, diethylpropion, cathine, and mazindol, with diethylpropion inducing it most frequently. Male subjects treated with these same drugs exhibited an unexpected effect: spontaneous ejaculations, potentially attributable to the combined effects on dopamine and serotonin signaling in brain regions regulating sexual function. Network analysis and Markov transition matrices revealed distinct behavioral profiles associated with head-weaving, which emerged as the dominant attractor state, suggesting potential mechanistic differences among these drugs. Collectively, this study provides a valuable database characterizing the behavioral side effects of appetite suppressants.

neuroscience↗
bioRxiv2025

The effect of chronic stress and chronic alcohol intake on behavior, brain structure, and functional connectivity in a rat model

Pathological chronic stress is stress exceeding the organisms ability to cope physiologically, which may act as a risk factor in the onset and relapse of alcohol use disorder. Chronic- restraint stress (CRS) and ethanol intake are independently known to induce changes in brain structure and function, however, their combined effects on neurodevelopment over long periods of time remains largely unexplored. We conducted an in vivo longitudinal rat model with three main goals. 1) to determine if chronic stress increases ethanol intake; 2) to determine the effect of chronic- stress and ethanol intake in behavioral measures, brain structure, and function; and 3) to investigate the effect of sex. This observational study included Wistar rats assigned to four groups: 1) ethanol consumption (EtOH+/CRS-), 2) stress exposure (EtOH-/CRS+), 3) both ethanol and stress exposure (EtOH+/CRS+), and 4) control group (EtOH-/CRS-). Our results showed that chronic stress did not affect ethanol intake but led to reduced body weight gain, elevated corticosterone levels, and impaired recognition memory. Structural MRI revealed that both exposures produced additive brain volume changes in regions such as the olfactory bulb, orbitofrontal cortex, caudate-putamen, hippocampus, and cerebellum. Functional connectivity analysis using network-based statistics identified disrupted cortical-subcortical connections. Results found here were sex-dependent in terms of volumetric changes (higher effects on males) and functional connectivity (higher effects on females). Findings suggest sex-dependent mechanisms where both chronic- ethanol intake and stress affect brain plasticity during neurodevelopment. Understanding these region-specific vulnerabilities is crucial for addressing alcohol use disorders and stress-related neuropathology. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC="FIGDIR/small/638122v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@27094dorg.highwire.dtl.DTLVardef@d3b8faorg.highwire.dtl.DTLVardef@155deeorg.highwire.dtl.DTLVardef@c9bb7b_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Created with bioRender C_FIG

neuroscience↗
bioRxiv2024

Cortical microtubules act as a template to organize nano-scale patterning of exocytosis

The microtubule cytoskeleton organizes exocytosis to enable cellular morphogenesis, but how non-centrosomal arrays control exocytotic site positioning remains poorly understood. Using elongating plant cells as a model, we developed quantitative methods to move beyond coarse correlation and reveal the precise spatial relationship between cortical microtubules and secretion. We identify KEULE, an essential SEC/MUNC protein, as a dynamic exocytosis marker that forms clusters with stereotyped assembly and disassembly kinetics at discrete secretion sites. Combining confocal microscopy with super-resolution analysis and Bayesian inference, we quantified microtubule-exocytosis positioning at nanometer precision. This analysis revealed that microtubules create [~]180 nm enrichment zones flanked by [~]520 nm depletion zones, generating a spatial pattern that replicates the cortical array structure. Unexpectedly, Bayesian inference showed strong evidence for a flat enrichment profile within these zones rather than peaked distributions. This flat profile, combined with enrichment zone widths exceeding the [~]50 nm reach of known tethering proteins, challenges a direct vesicle capture mechanism. Instead, our data support a membrane domain mechanism where microtubules organize lipid/protein composition to create preferred exocytosis territories. These findings establish quantitative spatial rules for how non-centrosomal microtubule arrays organize secretion.

cell biology↗
bioRxiv2024

Nucleus accumbens D2-expressing neurons: Balancing reward and licking disruption through rhythmic optogenetic stimulation

Dopamine D1 receptor-expressing neurons in the nucleus accumbens (NAc) are known to be critical for processing reward and regulating food intake. However, the role of D2-expressing neurons in this region remains less understood. This study employed optogenetic manipulations to investigate the role of NAc D2-expressing neurons in reward processing and sucrose consumption. Optogenetic activation of these neurons decreased sucrose preference (at 20 Hz), disrupted licking patterns (particularly at 8 and 20 Hz), and increased self-stimulation. Conversely, synchronizing stimulation with the animals licking rhythm mitigated licking disruption and even increased sucrose intake, suggesting a rewarding effect. Furthermore, 20 Hz stimulation (but not 8 Hz) induced place preference in a real-time place preference (RTPP) test. In contrast, inhibiting D2 neurons produced a negative hedonic state, although not reaching a complete aversion, influencing food choices in specific contexts. For instance, while the RTPP test per se was not sensitive enough to observe place aversion when mice could choose between consuming a high-fat diet (HFD) pellet in a context associated with or without inhibition of D2 neurons, they preferred to consume HFD on the non-inhibited side. This suggests that the palatability of HFD can unmask (but also overshadow) the negative hedonic state associated with D2 neuron inhibition. A negative reinforcement paradigm further confirmed the active avoidance behavior induced by D2 neuron inhibition. In conclusion, NAc D2 neuron inhibition induces a negative hedonic state, while activation has a dual effect--it is rewarding yet disrupts licking behavior--highlighting its complex role in reward and consummatory behavior. Importantly, self-paced stimulation, where the animal controls the timing of the stimulation by its licking behavior, offers a more efficient and natural approach for stimulating NAc activity.

neuroscience↗
bioRxiv2024

Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traits

Elderly individuals have higher disease susceptibility and lower vaccine responsiveness, highlighting the need to better comprehend the aging immune system and its clinical associations. Here we conducted a deep immune profiling study of 550 elderly individuals (61-94 years) and 100 young adults (22-38 years). Utilizing high-dimensional spectral flow cytometry to identify 97 immune cell populations and 48-plex cytokine profiling, we detailed intricate age-and sex-related changes in the elderly immune system at an unprecedented depth. Synthesizing information from clinical, laboratory, and immunological data through an integrative multi-block analysis, we reveal overarching systems-level signatures of aging, such as increased concentrations of specific cytokines and frequencies of defined innate and adaptive immune cell subpopulations. Extending this approach, we identified unique immune signatures of smoking, obesity, and several diseases including osteoporosis, heart failure and gout. Our systems biology approach enables to uncover new relationships between clinical characteristics and immunological traits.

immunology↗
bioRxiv2024

Muskelin acts as a substrate receptor of the highly regulated Drosophila CTLH E3 ligase during the maternal-to-zygotic transition

The maternal-to-zygotic transition (MZT) is a conserved developmental process where the maternally-derived protein and mRNA cache is replaced with newly made zygotic gene products. We have previously shown that in Drosophila the deposited RNA-binding proteins ME31B, Cup, and Trailer Hitch (TRAL) are ubiquitylated by the CTLH E3 ligase and cleared. However, the organization and regulation of the CTLH complex remain poorly understood in flies. In particular, Drosophila lacks an identifiable substrate adaptor, and the mechanisms restricting degradation of ME31B and its cofactors to the MZT are unknown. Here, we show that the developmental specificity of the CTLH complex is mediated by multi-pronged regulation, including transcriptional control by the transcription factor OVO and autoinhibition of the E3 ligase. One major regulatory target is the subunit Muskelin, which we demonstrate acts as a substrate adaptor for the Drosophila CTLH complex. Although conserved, Muskelin has structural roles in other species, suggesting a surprising functional plasticity. Finally, we find that Muskelin has few targets beyond the three known RNA binding proteins, showing exquisite target specificity. Thus, multiple levels of integrated regulation restrict the activity of the embryonic CTLH complex to early embryogenesis, seemingly with the goal of regulating three important RNA binding proteins.

developmental biology↗
bioRxiv2024

Sequential and dynamic coding of water-sucrose categorization in rat gustatory cortices

The gustatory system enables our conscious perception of sweetness, allowing us to distinguish sweet solutions from water. However, the neural mechanisms underlying this categorization process in rats remain poorly understood. We addressed this question by designing a novel sucrose categorization task in which rats classified varying sucrose concentrations against water. We found that in the anterior insular cortex (aIC) and orbitofrontal cortex (OFC), neural activity primarily encoded the categorical distinction between sucrose and water, rather than specific sucrose concentrations. Notably, aIC neurons encoded this distinction faster than OFC neurons. Conversely, the OFC slightly preceded the aIC in encoding choice information, although both cortices maintained parallel encoding of the rats choices. The encoding of sensory and categorical decisions was dynamic and sequential, forming a sequence of encoding neurons throughout the trial. These findings reveal that sucrose categorization relies on dynamic coding sequences in the neuronal activity of the aIC and OFC rather than static, long-lasting (sustained) neural representations. This dynamic coding, supported by single-cell population decoding and principal component analyses, suggests that the brain continuously updates its representation of sucrose categorization as new information emerges. Additionally, both the aIC and OFC rapidly encoded reward outcomes. Our data supports the notion that gustatory cortices employ sequential and dynamic coding to compute sensorimotor transformations, from taste detection to categorical taste decisions and reward processing. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/590344v2_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@20b8f0org.highwire.dtl.DTLVardef@4da81eorg.highwire.dtl.DTLVardef@586151org.highwire.dtl.DTLVardef@5d4469_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗
bioRxiv2024

The flow of reward information through neuronal ensembles in the accumbens

Reward information flows through neuronal ensembles in the nucleus accumbens shell (NAcSh), influencing decision-making. We investigated this phenomenon by training rats in a self-guided probabilistic choice task while recording single-unit activity in the NAcSh. We found that rats dynamically adapted their choices based on an internal representation of reward likelihood. Neuronal ensembles in the NAcSh act as dynamic modules to process different aspects of reward-guided behavior. Ensembles dynamically change composition and functional connections throughout reinforcement learning. The NAcSh forms a highly connected network with a heavy-tailed distribution and neuronal hubs, facilitating efficient reward information flow. Reward delivery evokes higher mutual information between ensembles and unifies network activity, while omission leads to less synchronization. Our recordings shed light on how reward information propagates through dynamically changing ensembles of neurons in the NAcSh. These functional ensembles exhibit flexible membership, dropping in and out and even shrinking in number as the rat learns to obtain (energy) rewards in an ever-changing environment. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=189 HEIGHT=200 SRC="FIGDIR/small/580379v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1e870org.highwire.dtl.DTLVardef@1434c90org.highwire.dtl.DTLVardef@157971aorg.highwire.dtl.DTLVardef@1812ca6_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗
bioRxiv2024

Parasite contingency loci and the evolution of host specificity: Simple sequence repeats mediate Bartonella adaptation to a wild rodent host

Parasites can adapt to better exploit their hosts on many scales, ranging from within an infection of a single individual to series of infections spanning multiple host species. However, little is known about how the genomes of parasites in natural communities evolve when they face diverse hosts. We investigated how Bartonella bacteria that circulate in rodent communities in the dunes of the Negev Desert in Israel adapt to different species of rodent hosts. We propagated 15 Bartonella populations through infections of either a single host species (Gerbillus andersoni or Gerbillus pyramidum) or alternating between the two. After 20 rodent passages, strains with de novo mutations replaced the ancestor in most populations. Mutations in two mononucleotide simple sequence repeats (SSRs) that caused frameshifts in the same adhesin gene dominated the evolutionary dynamics. They appeared exclusively in populations that encountered G. andersoni and altered the dynamics of infections of this host. Similar SSRs in other genes are conserved and exhibit ON/OFF variation in Bartonella isolates from the Negev Desert dunes. Our results suggest that SSR-based contingency loci could be important not only for rapidly and reversibly generating antigenic variation to escape immune responses but that they may also mediate the evolution of host specificity.

evolutionary biology↗
bioRxiv2023

Tesofensine, a novel antiobesity drug, silences GABAergic hypothalamic neurons

Obesity is a major global health epidemic that has adverse effects on both the people affected as well as the cost to society. Several anti-obesity drugs that target GLP-1 receptors have recently come to the market. Here we describe the effects of tesofensine, a novel anti-obesity drug that acts as a triple monoamine neurotransmitter reuptake inhibitor. We investigated its effects on weight loss and underlying neuronal mechanisms in mice and rats using various techniques. These include behavioral tasks, DeepLabCut videotaped analysis, electrophysiological ensemble recordings, optogenetic activation, and chemogenetic silencing of GABAergic neurons in the Lateral Hypothalamus (LH). We found that tesofensine induced greater weight loss in obese than lean rats, which was associated with changes in LH ensemble activity. In Vgat-ChR2 and Vgat-IRES-cre transgenic mice, we found for the first time that tesofensine inhibited a subset of LH GABAergic neurons, reducing their ability to promote feeding behavior, and chemogenetically silencing them enhanced tesofensines food-suppressing effects. Unlike phentermine, a dopaminergic appetite suppressant, tesofensine causes few, if any, head-weaving stereotypy at therapeutic doses. Most importantly, we found that tesofensine prolonged the weight loss induced by 5-HTP, a serotonin precursor, and blocked the body weight rebound that often occurs after weight loss. Behavioral studies on rats with the tastant sucrose indicated that tesofensines appetite suppressant effects are independent of taste aversion and do not directly affect the perception of sweetness or palatability of sucrose. In summary, our data provide new insights into the effects of tesofensine on weight loss and the underlying neuronal mechanisms, suggesting that tesofensine may be an effective treatment for obesity and that it may be a valuable adjunct to other appetite suppressants to prevent body weight rebound.

neuroscience↗
bioRxiv2023

Developmental trajectories of EEG aperiodic and periodic power suggest timing of thalamocortical development during infancy.

The development of neural circuits has long-lasting effects on brain function, yet our understanding of early circuit development in humans remains limited. Here, periodic EEG power features and aperiodic components were examined from longitudinal EEGs collected from 592 healthy 2-44 month-old infants, revealing age-dependent nonlinear changes suggestive of distinct milestones in early brain maturation. Consistent with the transient developmental progression of thalamocortical circuitry, we observe the presence and then absence of periodic alpha and high beta peaks across the three-year period, as well as the emergence of a low beta peak (12-20Hz) after six months of age. We present preliminary evidence that the emergence of the low beta peak is associated with higher thalamocortical-dependent, anesthesia-induced alpha coherence. Together, these findings suggest that early age-dependent changes in alpha and beta periodic peaks may reflect the state of thalamocortical network development.

neuroscience↗
bioRxiv2022

Highly multiplexed detection of microRNAs, proteins and small molecules using barcoded molecular probes and nanopore sequencing

Currently, most blood tests in a clinical setting only investigate a handful of markers. A low-cost, rapid, and highly multiplexed platform for the quantitative detection of blood biomarkers has the potential to advance clinical diagnostics beyond the single biomarker paradigm. In this study, we perform nanopore sequencing of barcoded molecular probes that have been engineered to recognise a panel of biological targets (miRNAs, proteins, and small molecules such as neurotransmitters), allowing for highly multiplexed simultaneous detection. Our workflow is rapid, from sample preparation to results in 1 hour. We also demonstrate that the strategy can be used to detect biomarkers directly from human serum without extraction or amplification. The established method is easily adaptable, as the number and type of targets detected can be greatly expanded depending on the application required.

biophysics↗
bioRxiv2021

VTA-IC dopaminergic inputs enhances the salience to consolidate aversive but not appetitive taste recognition memory via D1 receptors

Taste memory involves storing information through plasticity changes in the neural network of taste, including the insular cortex (IC) and ventral tegmental area (VTA), a critical provider of dopamine. Although a VTA-IC dopaminergic pathway has been demonstrated, its role to consolidate taste recognition memory remains poorly understood. We found that photostimulation of dopaminergic neurons in the VTA or VTA-IC dopaminergic terminals of TH-Cre mice increases the salience of a novel taste stimulus regardless of its hedonic value, without altering their taste palatability. Importantly, the inhibition of the D1-like receptor into the IC impairs the salience to facilitate consolidation of an aversive taste recognition memory. Finally, our results showed that VTA photostimulation improves the salience to consolidate a conditioned taste aversion memory through the D1-like receptor into the IC. It is concluded that the dopamine activity from the VTA into IC is required to increase the salience enabling the consolidation of a taste recognition memory. Notably, the D1-like receptor activity into the IC is required to consolidate both innate and learned aversive taste memories but not appetitive taste memory.

animal behavior and cognition↗