About

Ricardo C. Araneda is a Professor in the Department of Biology at the University of Maryland. His long-term research goal is to understand how neuromodulatory transmitters regulate the function of brain circuits and influence sensory processing, with a specific focus on olfaction as a model system. He investigates how neuromodulators such as acetylcholine and noradrenaline, along with basal forebrain GABAergic neurons, influence sensory processing using a multidisciplinary approach that includes electrophysiology, imaging, and targeted expression of optogenetic and chemogenetic probes. His research aims to examine how these neuromodulatory systems affect odor-guided behaviors in freely-behaving animals and to understand pathological changes in olfactory circuits associated with aging and neurodegenerative disorders. Additionally, his work expands to other areas through collaborative efforts, including the development of novel technologies for studying neuronal function, cell-based sensors, and mechanisms underlying hypothalamic control of food consumption.

Research topics

• Biology
• Neuroscience
• Cell biology
• Endocrinology
• Chemistry
• Internal medicine
• Biochemistry
• Medicine

Selected publications

• A fast and simple algorithm for accurate spike detection in HD-MEA recordings

  Journal of Neuroscience Methods · 2026-03-19

  articleOpen accessSenior authorCorresponding

  High density microelectrode arrays (HD-MEAs) provide a strong platform to study individual neuronal activity and neuronal network dynamics. However, the analysis of high volume and complex data present several challenges. Common spike detection methods based on Root-Mean-Square (RMS) threshold crossing underestimate the number of spikes during neuronal bursting, which frequently occurs in neuronal cultures. In addition, the detection of action potentials by multiple electrodes makes spike sorting a computationally expensive task. We optimized a previously described detection method, based on the scaled median of absolute deviations (MED) that is more accurate during high rates of neuronal firing. In addition, we added a step to de-duplicate (DP) spikes recorded on multiple electrodes, which enhanced the accuracy of MED. The combined method of detection and de-duplication (DP-MED) is less computationally expensive and easier to implement than popular sorting alternatives like Kilosort-4. During burst periods, the MED-based method detected over half of spikes that were undetected by the RMS-based method. To evaluate the performance of DP-MED, we simulated data that emulates neuronal activity recorded with HD-MEA. Across increasing firing rates, DP-MED shows more precision than Kilosort-4 but is slightly less accurate. After inducing high firing rate in cortical cultures with pharmacological stimulation, DP-MED detected a similar number of spikes than Kilosort-4, however, the analysis in Kilosort-4 was 40-fold more time-consuming. These results highlight the effectiveness of the DP-MED method in the context of drug screening using HD-MEAs. • We developed DP-MED, a fast and computationally efficient algorithm for precise spike detection for high density multi electrode array (HD-MEA) recordings. • DP-MED is more precise than commonly used RMS-based methods and its precision is less sensitive to neuronal bursting. • The performance of DP-MED is comparable to KiloSort-4, a widely used open-source spike sorting algorithm. • DP-MED is approximately 40 times faster than KiloSort-4 in processing high volume HD-MEA data.

  PublisherDOI

• Proteome-Driven Phenotyping of Identified Single Neurons in Intact Brain Tissue by Aspiration Patch Proteomics

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-26

  articleOpen access

  ABSTRACT Single-cell proteomics has advanced rapidly, but direct proteome measurements from identified neurons in intact brain tissue remain difficult because most workflows require cell isolation and recent patch-based studies have emphasized whole-soma retrieval. Here we show that aspiration-based patch proteomics enables deep proteome profiling of identified single neurons directly in acute mouse brain slices. We combined fluorescence-guided patch-clamp microsampling, minimal-loss bottom-up proteomics, and high-sensitivity capillary electrophoresis–timsTOF mass spectrometry to analyze partial somal aspirates from dopaminergic, parvalbumin, and serotonergic neurons in situ . The workflow identified more than 1,000 proteins from single-neuron samples under optimized conditions while consuming only about 0.25% of the processed digest per analysis. These proteomes were sufficient to separate biological replicates by neuronal phenotype, distinguish neuronal subtypes on the basis of protein expression alone, and define a conserved somal proteome shared across neuronal classes. Our results establish that controlled aspiration of partial somal material can support proteome-driven phenotyping without whole-soma retrieval, cell dissociation, or loss of native tissue context. Aspiration patch proteomics therefore provides an accessible route for subtype-level proteome phenotyping in intact brain tissue.

  PublisherOA PDFDOI

• A fast and simple algorithm for accurate spike detection in HD-MEA recordings

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-22

  articleOpen accessSenior authorCorresponding

  Abstract Background High density microelectrode arrays provide a strong platform to study individual neuronal activity and neuronal network dynamics. However, the analysis of high volume and complex data present several challenges. Common spike detection methods based on Root-Mean-Square (RMS) threshold crossing underestimate the number of spikes during neuronal bursting, which frequently occurs in neuronal cultures. In addition, the detection of action potentials by multiple electrodes makes spikes sorting a computationally expensive task. New Method We optimized a previously described detection method, based on the scaled median of absolute deviations (MED) that is more accurate during high rates of neuronal firing. In addition, we added a step to de-duplicate (DP) spikes recorded on multiple electrodes, which enhanced the accuracy of MED. The combined method of detection and de-duplication (DP-MED) is less computationally expensive and easier to implement than popular sorting alternatives like Kilosort-4. Results and Conclusions During burst periods, the MED-based method detected over half of spikes that were undetected by the RMS-based method. To evaluate the performance of DP-MED, we simulated data that emulates neuronal activity recorded with HD-MEA. Across increasing firing rates, DP-MED shows more precision than Kilosort-4 but is slightly less accurate. After inducing high firing rate in cortical cultures with pharmacological stimulation, DP-MED detected a similar number of spikes than Kilosort-4, however, the analysis in Kilosort-4 was 40-fold more time-consuming. These results highlight the effectiveness of the DP-MED method in the context of drug screening using HD-MEAs.

  PublisherOA PDFDOI

• Tanycyte-derived lactate activates astrocytic HCAR1 to modulate glutamatergic signaling and POMC neuron excitability

  Proceedings of the National Academy of Sciences · 2026-04-07

  articleOpen access

  Astrocytes and tanycytes play essential roles in hypothalamic metabolic sensing, yet how glial–glial communication translates metabolic cues into neuronal activity remains poorly understood. We previously demonstrated that tanycytes release lactate and that this metabolite modulates the activity of arcuate pro-opiomelanocortin (POMC) neurons. Here, we identify the lactate receptor, HCAR1, as a key mediator of tanycytes-astrocyte-neuron signaling in the arcuate nucleus. We show that HCAR1 is highly expressed in hypothalamic astrocytes and present in a subset of NPY neurons. In primary hypothalamic cultures, L-lactate, the endogenous agonist of HCAR1, elicited increases in astrocytic cytosolic Ca 2+ and stimulated glutamate release; both effects were abolished by HCAR1 silencing using siRNA. In parallel, L-lactate and 3Cl-HBA increased connexin hemichannel activity, and hemichannel inhibition reduced glutamate release. Consistent with these in vitro observations, focal intracellular glucose delivery to a single tanycyte in acute hypothalamic slices triggered rapid Ca 2+ elevations in neighboring astrocytes, revealing functional glial–glial communication in situ. Importantly, activation of astrocytic HCAR1 enhanced NMDA receptor-dependent slow inward currents and excitability in POMC neurons, an effect reproduced by pharmacological HCAR1 agonists and abolished by astrocytic HCAR1 silencing. Together, these findings uncover a glial metabolic relay in which tanycyte-derived lactate activates astrocytic HCAR1, promotes glutamate release, and enhances POMC neuron excitability, providing a mechanistic link between cerebrospinal fluid-borne glucose fluctuations and hypothalamic control of feeding.

  PublisherOA PDFDOI

• An anhydrobiotic cell line expressing odorant receptors shows odorant responses after dry storage

  Scientific Reports · 2025-10-10

  articleOpen access

  Odorant receptor-expressing cells have been shown to recognize various odors, which has brought them to the interest of the growing field of cell-based olfactory sensors. However, cell cultures are difficult to use outside a laboratory because of their continuous need for controlled conditions. In this study, the odorant receptor DmOr47a, the co-receptor DmOrco, and the calcium-sensing fluorescent protein GCaMP6f were stably expressed in a Pv11 cell line (Pv11-00443-Or47a), which is desiccatable. This cell line not only retained desiccation tolerance, but also showed dose-dependent fluorescence responses to the DmOr47a ligand pentyl acetate that were recovered 12 h after rehydration. Even more importantly, Pv11-00443-Or47a showed a response to the agonist of DmOrco just 1 h after rehydration, even upon inhibition of protein synthesis. This result demonstrates for the first time that a transmembrane protein can be dry-stored in an orthologous cell culture system. This work also constitutes an initial step towards the development of improved desiccatable sensing cells for use in portable devices.

  PublisherOA PDFDOI

• Remembrances of Dr. Michael V.L. Bennett by Iberoamerican Colleagues and Friends

  Neuroscience · 2024-01-23

  articleOpen access
  PublisherOA PDFDOI

• α2-Adrenergic modulation of Ih in adult-born granule cells in the olfactory bulb

  Frontiers in Cellular Neuroscience · 2023-01-06 · 1 citations

  articleOpen accessSenior authorCorresponding

  In the olfactory bulb (OB), a large population of axon-less inhibitory interneurons, the granule cells (GCs), coordinate network activity and tune the output of principal neurons, the mitral and tufted cells (MCs), through dendrodendritic interactions. Furthermore, GCs undergo neurogenesis throughout life, providing a source of plasticity to the neural network of the OB. The function and integration of GCs in the OB are regulated by several afferent neuromodulatory signals, including noradrenaline (NA), a state-dependent neuromodulator that plays a crucial role in the regulation of cortical function and task-specific decision processes. However, the mechanisms by which NA regulates GC function are not fully understood. Here, we show that NA modulates hyperpolarization-activated currents (I h ) via the activation of α 2 -adrenergic receptors (ARs) in adult-born GCs (abGCs), thus directly acting on channels that play essential roles in regulating neuronal excitability and network oscillations in the brain. This modulation affects the dendrodendritic output of GCs leading to an enhancement of lateral inhibition onto the MCs. Furthermore, we show that NA modulates subthreshold resonance in GCs, which could affect the temporal integration of abGCs. Together, these results provide a novel mechanism by which a state-dependent neuromodulator acting on I h can regulate GC function in the OB.

  PublisherOA PDFDOI

• Review for "Carbachol Increases Locus Coeruleus Activation by Targeting Noradrenergic Neurons, Inhibitory Interneurons, and Inhibitory Synaptic Transmission"

  2022-10-18

  peer-review1st authorCorresponding
  PublisherDOI

• Review for "Carbachol Increases Locus Coeruleus Activation by Targeting Noradrenergic Neurons, Inhibitory Interneurons, and Inhibitory Synaptic Transmission"

  2022-07-19

  peer-review1st authorCorresponding
  PublisherDOI

• GKRP-dependent modulation of feeding behavior by tanycyte-released monocarboxylates

  Theranostics · 2022-01-01 · 7 citations

  articleOpen access

  Objectives: Glucokinase Regulatory Protein (GKRP) is the only known endogenous modulator of glucokinase (GK) localization and activity to date, and both proteins are localized in tanycytes, radial glia-like cells involved in metabolic and endocrine functions in the hypothalamus. However, the role of tanycytic GKRP and its impact on the regulation of feeding behavior has not been investigated. Here, we hypothesize that GKRP regulates feeding behavior by modulating tanycyte-neuron metabolic communication in the arcuate nucleus. Methods: We used primary cultures of tanycytes to evaluate the production of lactate and -hydroxybutyrate (HB). Similarly, we examined the electrophysiological responses to these metabolites in pro-opiomelanocortin (POMC) neurons in hypothalamic slices. To evaluate the role of GKRP in feeding behavior, we generated tanycyte-selective GKRP-overexpressing and GKRP-knock down mice (GKRP t -OE and GKRP t -KD respectively) using adenovirus-mediated transduction. Results: We demonstrated that lactate release induced by glucose uptake is favored in GKRP-KD tanycytes. Conversely, tanycytes overexpressing GKRP showed an increase in HB efflux induced by low glucose concentration. In line with these findings, the excitability of POMC neurons was enhanced by lactate and decreased in the presence of HB. In GKRP t -OE rats, we found an increase in post-fasting food avidity, whereas GKRP t -KD caused a significant decrease in feeding and body weight, which is reverted when MCT1 is silenced. Conclusion: Our study highlights the role of tanycytic GKRP in metabolic regulation and positions this regulator of GK as a therapeutic target for boosting satiety in patients with obesity problems.

  PublisherOA PDFDOI

Recent grants

• The Olfactory Bulb-Entorhinal Cortex Axis as an Early Biomarker for Alzheimers Disease

  NIH · $1.6M · 2015–2022

• Neuromodulation in the olfactory system

  NIH · $1.8M · 2009–2015

Frequent coauthors

• Pablo S. Villar

  University of Maryland, College Park

  14 shared

• Stuart Firestein

  Columbia University

  11 shared

• Zita Peterlin

  Firmenich (United States)

  8 shared

• Richard S. Smith

  8 shared

• Alexia Nunez-Parra

  University of Chile

  7 shared

• R. Suzanne Zukin

  Albert Einstein College of Medicine

  6 shared

• Ruilong Hu

  Broad Institute

  6 shared

• Krista Krahe

  University of Maryland, College Park

  6 shared

Education

• PhD, Neuroscience

  Yeshiva University Albert Einstein College of Medicine

  1997

• BS. Biochemistry

  Universidad de Concepción

  1986