Biology subjects

Kennedy, A.

Publications and source records attributed to Kennedy, A..

At least 19 recordsLinked to original sources

bioRxiv2026

A community benchmark enables high-resolution, cross-lab quantification of mouse social behavior

Social behavior is a sensitive readout of brain state, but quantifying rodent social behavior at scale has relied on siloed, lab-specific tools. We assembled Days of our Mice (DooM), a benchmark of manually annotated video and pose tracking spanning 15 laboratories and 33 social and solitary behaviors, and hosted a community behavior classification challenge. We built on challenge solutions to develop the High-Dimensional Rodent Annotator (HiDRA), a behavior classification tool that generalizes to labs unseen during training and learns cross-lab movement features. Applied without retraining to experimental data, HiDRA resolves line-specific and state-dependent behavioral fingerprints with strong generalizability and reproducibility, establishing high-resolution, shareable social phenotyping as a scalable readout of brain and internal state. We release the DooM dataset and HiDRA classifiers as open resources.

neuroscience↗

bioRxiv2026

Adrenal Gland Macrophage-derived TGF-β Governs Vascular Permeability to Drive Monocyte Recruitment during Stress

The adrenal glands are central regulators of systemic stress responses through tightly controlled glucocorticoid production. Yet, the contribution of local immune-vascular interactions to adrenal stress adaptation remains poorly understood. Here, we investigated the role of adrenal gland macrophages in coordinating stress-induced immune remodeling and vascular function. By integrating single-cell RNA sequencing datasets across four distinct stress models, including acute cold exposure, chronic social defeat, chronic inflammation, and systemic Candida albicans infection, we identified a conserved increase in monocyte recruitment to the adrenal gland, accompanied by dynamic macrophage transitions. Comparative transcriptomic and ligand-receptor analyses identified transforming growth factor-{beta} (TGF{beta}) as a dominant macrophage-derived signal targeting adrenal endothelial cells across all stress conditions. Pharmacological blockade of TGF{beta} receptor signaling reduced endothelial activation, vascular permeability, and monocyte infiltration into the adrenal gland following stress, without directly altering resident macrophage numbers. Using genetic fate-mapping and conditional knockout models, we demonstrate that macrophage-derived, but not endothelial-derived, TGF{beta} is required to promote enhanced endothelial adhesion molecule expression, vascular fenestration, permeability, and efficient monocyte recruitment. Loss of macrophage TGF{beta} production also led to exacerbated systemic stress hormone levels. Together, these findings uncover a previously unrecognized macrophage-endothelial axis in the adrenal gland, whereby macrophage-derived TGF{beta} regulates vascular properties to support immune cell recruitment and stress adaptation. This immune-vascular crosstalk provides new mechanistic insights into adrenal homeostasis and suggests potential therapeutic avenues for disorders associated with dysregulated chronic stress.

immunology↗

bioRxiv2026

Top-down regulation of ingestive behavior fragmentation

AbstractIn natural environments, animals rarely feed continuously to satiation; instead, feeding occurs in brief bouts separated by pauses. This fragmentation is thought to balance internal drives with external demands, yet its underlying neural mechanisms remain unclear. By combining bidirectional neural activity mapping and behavioral phenotyping, we identify a projection from the dorsal subiculum (dSub) of the hippocampus to the mammillary body (MB) as a key regulator of this fragmentation. Activity along the dSub-MB pathway tracks and gates the duration of individual feeding bouts, independent of homeostatic state. A simple bistable attractor model captures both dSub-MB neural dynamics and associated behaviors across optogenetic and behavioral perturbations. Together, these findings identify a top-down circuit mechanism that implements action selection in a naturalistic setting.

neuroscience↗

bioRxiv2026

Latent Regulatory Programs Generate Synthetic T Cell States with Enhanced Therapeutic Potential

Transcription factors (TFs) govern cell fate through coordinated gene-regulatory networks, yet the full potential of these networks to generate non-native, therapeutically advantageous cell states in vivo remains largely unexplored. We hypothesized that systematic gain-of-function (GOF) overexpression of TFs in CD8 T cells, central mediators of immune protection, could reveal latent, or "hidden," regulatory programs capable of generating synthetic T cell states with therapeutic utility. To test this, we developed single-cell GOF sequencing (scGOF-seq), a multiplexed platform for unbiased, in vivo mapping of GOF effects on T cell fate in immunocompetent mouse models of infection and cancer. scGOF-seq uncovered unexpected regulators of T cell differentiation and accumulation, including SOX2, OCT4, and GATA2, which are normally silenced during T cell differentiation. Notably, outside its native regulatory context, supraphysiologic cMyc GOF reprogrammed CD8 T cells into a synthetic stem-effector hybrid state, enabling >5,000-fold antigen-dependent expansion and antitumor activity, contrasting sharply with its native function in driving terminal differentiation. scGOF-seq further identified TF modules that cooperate with cMyc GOF to promote robust CD8 T cell responses in solid tumors. Together, these findings establish GOF perturbation as a powerful strategy for revealing latent immune regulatory programs and engineering synthetic immune states with therapeutic potential. One-Sentence SummaryIn vivo single-cell gain-of-function screening reveals latent transcriptional programs that can reprogram T cells into highly functional synthetic states.

immunology↗

bioRxiv2025

Haplotype-resolved reference genomes of the sea turtle clade unveil ultra-syntenic genomes with hotspots of divergence

BackgroundReference genomes for the entire sea turtle clade have the potential to reveal the genetic basis of traits driving the ecological and phenotypic diversity in these ancient and iconic marine species. Furthermore, these genomic resources can support conservation efforts and deepen our understanding of their unique evolution. ResultsWe present haplotype-resolved, chromosome-level reference genomes and high-quality gene annotations for five sea turtle species. This completes the catalog of reference genomes of the entire sea turtle clade when combined with our previously published reference genomes. Our analysis reveals remarkable genome synteny and collinearity across all species, despite the clades origin dating back more than 60 million years. Regions of high interspecific genetic distance and intraspecific genetic diversity are consistently clustered in genomic hotspots, which are enriched with genes coding for immune response proteins, olfactory receptors, zinc fingers, and G-protein-coupled receptors. These hotspot regions may offer insights into the genetic mechanisms driving phenotypic divergence among species, and represent areas of significant adaptive potential. Ancient demographic analysis revealed a synchronous population expansion among sea turtle species during the Pleistocene, with varying magnitudes of demographic change, likely shaped by their diverse ecological adaptations, and biogeographic contexts. ConclusionsOur work provides genomic resources for exploring genetic diversity, evolutionary adaptations, and demographic histories of sea turtles. We outline genomic regions with increased diversity, linked to immune response, sensory evolution, and adaptation to varying environments that have historically been subject to strong diversifying selection, and likely will underpin sea turtles responses to future environmental change. These reference genomes can assist conservation by providing insights into the demographic and evolutionary processes that sustain and threaten these iconic species.

genomics↗

bioRxiv2024

Expert Panel Curation of 31 Genes in Relation to Limb Girdle Muscular Dystrophy

IntroductionLimb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD. MethodsThe ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene-disease relationships (GDR) using the ClinGen gene-disease clinical validity framework to evaluate 31 genes implicated in LGMD. ResultsThe GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (CAPN3, COL6A1, COL6A2, COL6A3) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as Definitive, 4 (11%) as Moderate and 1 (3%) as Limited. Two genes, POMGNT1 and DAG1, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD. ConclusionsThe expert-reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case-level data that help clarify disputed or novel LGMD associations.

genetics↗

bioRxiv2024

Rigid, bivalent CTLA-4 binding to CD80 is required to disrupt the cis CD80 / PD-L1 interaction

The CTLA-4 and PD-1 checkpoints control immune responses to self-antigens and are key targets in cancer immunotherapy. Both pathways are connected via a cis interaction between CD80 and PD-L1, the ligands for CTLA-4 and PD-1 respectively. This cis interaction prevents PD-1 binding to PD-L1 but is reversed by CTLA-4 trans-endocytosis of CD80. However, the mechanism by which CTLA-4 selectively removes CD80 but not PD-L1 is unclear. Here we show that CTLA-4 - CD80 interactions are unimpeded by PD-L1 and that CTLA-4 binding with CD80 does not displace PD-L1 per se. Rather, both the rigidity and bivalency of the WT CTLA-4 molecule is required to orientate CD80 such that PD-L1 interactions are no longer permissible. Moreover, soluble CTLA-4 released PD-L1 only at specific expression levels of CD80 and PD-L1, whereas CTLA-4 trans-endocytosis released PD-L1 in all conditions. These data show that PD-L1 release from CD80 is driven by biophysical factors associated with orientation and bivalent cross-linking of proteins in the cell membrane and that trans-endocytosis of CD80 efficiently promotes PD-L1 availability.

immunology↗

bioRxiv2024

Biosynthesis of Arcyriaflavin F from Streptomyces venezuelae ATCC 10712

Indolocarbazoles are natural products with a broad spectrum of reported bioactivities. A distinct feature of indolocarbazole biosynthesis is the modification of the indole and maleimide rings by regioselective tailoring enzymes. Here, we study a new indolocarbazole variant, which is encoded by the acfXODCP genes from Streptomyces venezuelae ATCC 10712. First, we characterise this pathway by expressing the acfXODCP genes in Streptomyces coelicolor, which led to the production of a C-5/C-5-dihydroxylated indolocarbazole. We name this new product arcyriaflavin F. Second, we demonstrate the flavin-dependent monooxygenase AcfX catalyses the C-5/C-5 dihydroxylation of the unsubstituted arcyriaflavin A into arcyriaflavin F. Interestingly, AcfX shares homology to EspX from erdasporine A biosynthesis, which instead catalyses a single C-6 indolocarbazole hydroxylation. In summary, we report a new indolocarbazole biosynthetic pathway and a regioselective C-5 indole ring tailoring enzyme AcfX. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=46 SRC="FIGDIR/small/589956v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@c0c397org.highwire.dtl.DTLVardef@16915dforg.highwire.dtl.DTLVardef@1ae538org.highwire.dtl.DTLVardef@1bef4ed_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Development of MHC Class I Blocking Peptides to Target Metabolic Dysfunction-Associated Steatohepatitis CD8+ T Cell Activation

MHC class I molecules play a crucial role in the immune system by presenting peptides derived from intracellular proteins to cytotoxic T lymphocytes (CTLs). This process is essential for immune surveillance and eliminating infected or malignant cells. In some diseases, the immune system fails to recognize and eliminate abnormal cells, leading to disease progression. Under conditions of metabolic dysfunction-associated steatohepatitis (MASH), subsets of CD8+ T cells have been identified as pathogenic, leading to inflammation and fibrosis. Therefore, explicitly targeting factors responsible for T cell activation may be necessary to prevent the onset of MASH and future complications such as cirrhosis or hepatocellular carcinoma. We have identified a specific MHC class I antigen that activates hepatic and splenic CD8+ T cells isolated from MASH mice. To specifically target the antigen, we developed two MHC H2-Kb blocking peptides, MHCP3 and MHCP5, that competitively inhibit the Ncf2 peptide from binding to H2-Kb and reduce activation and proliferation of CD8+ T cells. By inhibiting the recognition of specific antigens, these blocking peptides may prevent the activation of CD8+ T cells and progression of MASH.

immunology↗

bioRxiv2024

A parabrachial hub for the prioritization of survival behavior

Long-term sustained pain in the absence of acute physical injury is a prominent feature of chronic pain conditions. While neurons responding to noxious stimuli have been identified, understanding the signals that persist without ongoing painful stimuli remains a challenge. Using an ethological approach based on the prioritization of adaptive survival behaviors, we determined that neuropeptide Y (NPY) signaling from multiple sources converges on parabrachial neurons expressing the NPY Y1 receptor to reduce sustained pain responses. Neural activity recordings and computational modeling demonstrate that activity in Y1R parabrachial neurons is elevated following injury, predicts functional coping behavior, and is inhibited by competing survival needs. Taken together, our findings suggest that parabrachial Y1 receptor-expressing neurons are a critical hub for endogenous analgesic pathways that suppress sustained pain states.

neuroscience↗

bioRxiv2024

The MYCN 5' UTR as a therapeutic target in neuroblastoma

Tumor cell amplification of the MYCN transcription factor is seen in half of patients with high-risk neuroblastoma, where it functions as an oncogenic driver associated with metastatic disease and poor survival. Yet, direct targeting of MYCN has been met with little success, prompting efforts to inhibit its expression at multiple levels. MYCN-amplified neuroblastoma cells have an increased requirement for protein synthesis to meet the overwhelming transcriptional burden imposed by oncogenic MYCN. Here, we take advantage of this vulnerability to interrogate the therapeutic potential of inhibiting the activity of the eukaryotic translation initiation factor 4A1 (eIF4A1), an RNA-helicase responsible for resolving structural barriers such as polypurine preponderance within 5' untranslated regions (UTRs). We observed that eIF4A1 is a key regulator of transcript-specific mRNA recruitment in MYCN-overexpressing neuroblastomas and MYCN-associated transcripts rank highly in polypurine-rich 5' UTR sequences, the majority of which have critical roles in cell proliferation. Using CMLD012824, a novel synthetic amidino-rocaglate (ADR) derivative, we demonstrate selectively increased eIF4A1 affinity for polypurine-rich 5' UTRs, including the MYCN mRNA, leading to translation inhibition and cytotoxicity in human neuroblastoma cell lines and animal models. Through ribosome profiling and PAR-CLIP analysis, we show that ADR-mediated clamping of eIF4A1 onto mRNA spans the full lengths of target transcripts, whereas translational inhibition is mediated selectively through 5' UTR binding. Both cap-dependent and cap-independent translation of MYCN are disrupted, pointing to the ability of CMLD012824 to disrupt non-canonical translation initiation. Our studies provide insights into the functional role of eIF4A1 in meeting the increased protein synthesis demands of MYCN-amplified neuroblastoma and suggest that its disruption may be therapeutically beneficial in this disease.

cancer biology↗

bioRxiv2024

Wild bird mass mortalities in eastern Canada associated with the Highly Pathogenic Avian Influenza A(H5N1) virus, 2022

In 2022, a severe outbreak of clade 2.3.4.4b Highly Pathogenic Avian Influenza (HPAI) H5N1 virus resulted in unprecedented mortality among wild birds in eastern Canada. Tens of thousands of birds were reported sick or dead, prompting a comprehensive assessment of mortality spanning the breeding season between April 1 and September 30, 2022. Mortality reports were collated from federal, Indigenous, provincial, and municipal agencies, the Canadian Wildlife Health Cooperative, non-governmental organizations, universities, and citizen science platforms. A scenario analysis was conducted to refine mortality estimates, accounting for potential double counts from multiple sources under a range of spatial and temporal overlap. Correcting for double counting, an estimated 40,966 wild birds were reported sick or dead in eastern Canada during the spring and summer of 2022. Seabirds and sea ducks, long-lived species that are slow to recover from perturbations, accounted for 98.7% of reported mortalities. Mortalities were greatest among Northern Gannets (Morus bassanus; 26,193), Common Murres (Uria aalge; 8,133), and American Common Eiders (Somateria mollissima dresseri; 1,945), however, these figures underestimate total mortality as they exclude unreported deaths on land and at sea. In addition to presenting mortality estimates, we compare mortalities with known population sizes and trends and make an initial assessment of whether population-level impacts are possible for the Northern Gannet, a species that has suffered significant global mortality, and two harvested species, Common Murre and American Common Eider, to support management decisions. We hypothesize that population-level impacts in eastern Canada are possible for Northern Gannets and American Common Eiders but are unlikely for Common Murres. This study underscores the urgent need for further research to understand the broader ecological ramifications of the HPAI outbreak on wild bird populations.

zoology↗

bioRxiv2023

Selective advantage of mutant stem cells in clonal hematopoiesis occurs by attenuating the deleterious effects of inflammation and aging

Clonal hematopoiesis (CH) arises when hematopoietic stem cells (HSC) acquire mutations in genes, including DNMT3A and TET2, conferring a competitive advantage through a mechanism that remains unclear. To gain insight into how CH mutations enable gradual clonal expansion, we used single-cell multi-omics with high-fidelity genotyping on CH bone marrow samples. Most of the selective advantage of mutant cells occurs within HSCs. DNMT3A and TET2-mutant clones expand further in early progenitors, while TET2 mutations accelerate myeloid maturation in a dose-dependent manner. Unexpectedly, both mutant and non-mutant HSCs from CH samples are enriched for inflammatory and aging transcriptomic signatures, compared to HSC from non-CH samples, revealing a non-cell autonomous mechanism. However, DNMT3A and TET2-mutant HSCs have an attenuated inflammatory response relative to wild-type HSCs within the same sample. Our data support a model whereby CH clones are gradually selected because they are more resistant to the deleterious impact of inflammation and aging.

cancer biology↗

bioRxiv2023

Striatal ensemble activity in an innate naturalistic behavior

Self-grooming is an innate, naturalistic behavior found in a wide variety of organisms. The control of rodent grooming has been shown to be mediated by the dorsolateral striatum through lesion studies and in-vivo extracellular recordings. Yet, it is unclear how populations of neurons in the striatum encode grooming. We recorded single-unit extracellular activity from populations of neurons in freely moving mice and developed a semi-automated approach to detect self-grooming events from 117 hours of simultaneous multi-camera video recordings of mouse behavior. We first characterized the grooming transition-aligned response profiles of striatal projection neuron and fast spiking interneuron single units. We identified striatal ensembles whose units were more strongly correlated during grooming than during the entire session. These ensembles display varied grooming responses, including transient changes around grooming transitions or sustained changes in activity throughout the duration of grooming. Neural trajectories computed from the identified ensembles retain the grooming related dynamics present in trajectories computed from all units in the session. These results elaborate striatal function in rodent self-grooming and demonstrate that striatal grooming-related activity is organized within functional ensembles, improving our understanding of how the striatum guides action selection in a naturalistic behavior.

neuroscience↗

bioRxiv2022

Monkey-to-human transfer of brain computer interface decoders

Intracortical brain-computer interfaces (iBCIs) enable paralyzed persons to generate movement, but current methods require large amounts of both neural and movement-related data to be collected from the iBCI user for supervised decoder training. We hypothesized that the low-dimensional latent neural representations of motor behavior, known to be preserved across time, might also be preserved across individuals, and allow us to circumvent this problem. We trained a decoder to predict the electromyographic (EMG) activity for a "source" monkey from the latent signals of motor cortex. We then used Canonical Correlation Analysis to align the latent signals of a "target" monkey to those of the source. These decoders were as accurate across monkeys as they were across sessions for a given monkey. Remarkably, the same process with latent signals from a human participant with tetraplegia was within 90% of the with-monkey decoding across session accuracy. Our findings suggest that consistent representations of motor activity exist across animals and even species. Discovering this common representation is a crucial first step in designing iBCI decoders that perform well without large amounts of data and supervised subject-specific tuning.

neuroscience↗

bioRxiv2022

Using adversarial networks to extend brain computer interface decoding accuracy over time

Existing intracortical brain computer interfaces (iBCIs) transform neural activity into control signals capable of restoring movement to persons with paralysis. However, the accuracy of the "decoder" at the heart of the iBCI typically degrades over time due to turnover of recorded neurons. To compensate, decoders can be recalibrated, but this requires the user to spend extra time and effort to provide the necessary data, then learn the new dynamics. As the recorded neurons change, one can think of the underlying movement intent signal being expressed in changing coordinates. If a mapping can be computed between the different coordinate systems, it may be possible to stabilize the original decoders mapping from brain to behavior without recalibration. We previously proposed a method based on Generalized Adversarial Networks (GANs), called "Adversarial Domain Adaptation Network" (ADAN), which aligns the distributions of latent signals within underlying low-dimensional neural manifolds. However, ADAN was tested on only a very limited dataset. Here we propose a method based on Cycle-Consistent Adversarial Networks (Cycle-GAN), which aligns the distributions of the full-dimensional neural recordings. We tested both Cycle-GAN and ADAN on data from multiple monkeys and behaviors and compared them to a linear method based on Procrustes Alignment of axes provided by Factor Analysis (PAF). Both GAN-based methods outperformed PAF. Cycle-GAN and ADAN (like PAF) are unsupervised and require little data, making them practical in real life. Overall, Cycle-GAN had the best performance and was easier to train and more robust than ADAN, making it ideal for stabilizing iBCI systems over time. Significance StatementThe inherent instabilities in the neural signals acquired by intracortical microelectrode arrays cause the performance of an intracortical brain computer interface (iBCI) decoder to drop over time, as the movement intent signal must essentially be recorded from neurons representing an ever-changing coordinate system. Here, we address this problem using Generative Adversarial Networks (GANs) to align these coordinates and compare their success to another, recently proposed linear method that uses Factor Analysis and Procrustes alignment. Our proposed methods are fully unsupervised, can be trained quickly, and require remarkably little new data. These methods should give iBCI users access to decoders with unchanging dynamics, and without the need for periodic supervised recalibration.

neuroscience↗

bioRxiv2022

Early Life Exposure to Queen Mandibular Pheromone Mediates Persistent Transcriptional Changes in the Brain of Honey bee Foragers

How behavior in insect societies is regulated remains a fundamental question in sociobiology. In hymenopteran societies, the queen plays a crucial role in regulating group behavior by affecting individual behavior, physiology, and lifespan through worker gene expression. Honey bee (Apis mellifera) queens signal their presence via the queen mandibular pheromone (QMP). While QMP has been shown to influence the behavior of young workers, we know little about its long-term molecular impacts on workers and whether these pheromone effects depend on an early sensitive period in the life of a worker. Here we demonstrate that QMP treatment strongly impacts long-term forager gene expression in the mushroom bodies, antennal lobes, and antennae, but only if bees were treated early in life (1-2 days of age). Contrary to our expectation, foraging activity was not impacted by QMP treatment in the long-term, but genes important for division of labor, learning, chemosensory perception and aging were differentially expressed in the antennae and brain tissues, suggesting that QMP influences diverse physiological and behavioral processes in workers. Overall, our study suggests a sensitive period early in the life of workers, where the queens presence or absence has strong and potentially livelong effects on transcriptional activity in the central and peripheral nervous system. Significance statementDespite our increasing understanding of how social cues affect gene expression and behavior in social animals, we still know little about the importance of sensitive periods in cue perception for the long-term regulation of gene expression. Honey bees live in complex societies and queen pheromones play a central role in the regulation of worker behavior and division of labor. We tested the exposure to queen pheromone presence and found that there is a sensitive period in the early adult life of workers. Understanding and identifying sensitive periods and their effect on long-term gene transcription in workers in response to changes in the environment will lay an important foundation for a better understanding of how queens shape colony life.

animal behavior and cognition↗

bioRxiv2022

An approximate line attractor in the hypothalamus that encodes an aggressive internal state

The hypothalamus plays a key role in regulating innate behaviors. It is widely believed to function as a system of labeled lines, containing behavior-specific neurons with characteristic transcriptomic and connectomic profiles. This view however fails to explain why, although activation of estrogen receptor-1 (Esr1) expressing neurons in the ventromedial hypothalamus (VMHvl) promotes aggression, few VMHvl neurons are tuned to attack. To address this paradox, we adopted an unsupervised dynamical systems framework to analyze population activity among VMHvlEsr1 neurons during aggression. We discovered that this activity contains an "integration" dimension exhibiting slow-ramping dynamics and persistent activity that correlates with escalating aggressiveness. These dynamics are implemented as an approximate line attractor in state space. Our analysis suggests a function for VMHvl to encode the intensity of behavior-relevant motive states using line attractors. This view reconciles observational and perturbational studies of VMHvl, and reveals a new mode of neural computation in the hypothalamus.

neuroscience↗