Lab Publications
Papers listed in reverse-chronology.
On the Cover
2026
AN ORAL FENTANYL SELF-ADMINISTRATION MODEL REVEALS DISSOCIABLE ESCALATION AND RELAPSE PHENOTYPES IN OUTBRED VS INBRED MICE.
bioRxiv. 2026 Aug 4:2026.07.30.741697. doi: 10.64898/2026.07.30.741697 [PREPRINT] [FULL DOWNLOAD]
Fentanyl-related overdose deaths now commonly involve non-injection routes, yet preclinical opioid self-administration is modeled predominantly intravenously. Here we establish an oral fentanyl self-administration procedure in male and female inbred C57BL/6 and outbred CD1 mice that measures volitional intake, cue-driven seeking, extinction, and relapse. Mice self-administered oral fentanyl (70 μg/mL) on a fixed-ratio 1 schedule across fifteen 3-hour sessions, followed by ten extinction sessions and a cued reinstatement test. A separate cohort underwent between-session dose thresholding across a quarter-log series from 222 to 22 μg/mL. Seventy-five percent of mice acquired self-administration, with similar rates across genetic background and sex. Responding increased as fentanyl concentration fell, indicating dose-sensitivity toward a preferred drug level. C57BL/6 mice escalated intake and lever pressing across sessions, responded persistently early in extinction before declining, and reinstated pressing to a conditioned cue. CD1 mice consumed high levels from the outset with limited escalation and showed neither extinction nor cued reinstatement of pressing, but shortened their reward-port approach latency when cues returned. This shows that lever presses alone would have misclassified them as weakly conditioned. A composite severity score summing seven components of fentanyl-use risk varied continuously rather than splitting into high and low groups, even among inbred mice. Sex differences were largely confined to C57BL/6 mice, in which females showed stronger cue association and higher severity scores than males. These results reveal separable escalation-prone and relapse-prone phenotypes that track genetic background. Protocols, hardware specifications, and analysis code are openly available, lowering the barrier to adopting oral fentanyl self-administration.
SOCIAL AGENCY BUFFERS PAIN SENSITIVITY DURING A CRITICAL WINDOW FOLLOWING SPARED NERVE INJURY.
bioRxiv. 2026 Jul 21:2026.07.15.738734. doi: 10.64898/2026.07.15.738734 [PREPRINT] [FULL DOWNLOAD]
Background: Social buffering of pain, where social contact blunts pain intensity, is well established. However, the degree to which agency over social contact, rather than passive social exposure alone, modifies pain intensity or social behavior is unclear. Methods: Using a social operant self-administration procedure in which mice lever-press for access to their pair-housed partner, we show that voluntary social engagement gates pain after spared nerve injury (SNI). After 8 days of training, mice underwent SNI and then regained access to social self-administration either 1 day (Early) or 5 days (Delayed) following surgery. We compared these mice to groups without social self-administration access, non-contingent social-access, and food self-administration. We assessed changes in pain, or mechanical allodynia, via the von Frey test. Results: Early access to social self-administration after SNI preserved pre-injury social reinforcement and buffered pain. Delayed access similarly preserved social reinforcement but failed to buffer allodynia, revealing an early post-injury critical window for social buffering of pain. Females were more sensitive to both SNI and disrupted social access, while males maintained social reward-seeking after SNI when given early access and showed robust social buffering of pain. Non-contingent (involuntary) social self-administration did not modify pain, nor did food self-administration. Conclusions: There is an early critical window during which voluntary social interactions buffer pain after nerve injury. These results highlight social reward agency and proximity to injury as key variables, since pain outcomes do not generalize to food reward, non-contingent social reward, or delayed access to social reward.
SUBCORTICAL RECRUITMENT DISSOCIATES ISOFLURANE EMERGENCE FROM DISTINCT WAKEFUL STATES IN MICE.
bioRxiv. 2026 May 19:2026.05.15.725233. doi: 10.64898/2026.05.15.725233 [PREPRINT] [FULL DOWNLOAD]
Emergence from general anesthesia, defined by a recovery of consciousness to the wakeful state, is a clinically consequential state transition that remains a passive process dependent on drug clearance. Despite the critical use of anesthesia, the neural circuitry underlying behavioral recovery remains poorly defined. Here, we map whole-brain neural activity during emergence from isoflurane anesthesia in mice using Fos immunolabeling, tissue clearing, and light-sheet microscopy. This approach enables unbiased quantification of neural activity at cellular resolution across the intact whole brain and supports subsequent network analysis. Rather than resembling wakefulness, emergence exhibits widespread cortical suppression alongside selective activation of discrete subcortical nuclei. This pattern of activity includes both previously implicated arousal-related regions and lesser-studied structures linked to respiratory, autonomic, interoceptive, and cerebellar function. By comparing emergence to two behaviorally distinct wakeful control states, we find that control state selection substantially shapes interpretation of whole-brain activity maps. This establishes dual-state comparisons as a broadly useful strategy for state-dependent circuit mapping. Functional network analysis further elucidates candidate central regions that strongly covary together during emergence, with the most integrated region being the ventral orbital cortex. Together, we find that emergence from isoflurane anesthesia reflects selective subcortical recruitment rather than broad global reactivation toward wakefulness.
ATTACK REPERTOIRES IN OUTBRED MALE CD1-MICE ARE ASSOCIATED WITH NUCLEUS ACCUMBENS NEUROLIGIN-2.
eNeuro. 2026 Apr 24;13(5):ENEURO.0471-25.2026. doi: 10.1523/ENEURO.0471-25.2026 [FULL DOWNLOAD]
Aggression may be behaviorally distinguished by reactive or appetitive properties. Here, we use a model of operant aggression administration, in which outbred male CD-1 mice lever press (contingent) or do not lever press (noncontingent) to attack an intruder mouse, to examine behavioral differences in aggression reinforcement. Contingent reinforcement identifies the behavioral and neural basis of appetitive, or rewarding, aggression self-administration, while noncontingent reinforcement isolates reactive, or involuntary, components. Females are not used in this study due to their low propensity to attack. We applied supervised machine-guided behavioral classification and Shapley additive scores (SHAP) to describe differences and similarities in attack behavior features. We find that behavioral sequences of an attack bout are similar whether aggression reinforcement is contingent or noncontingent, though underlying neural mechanisms differ. Fos immunolabeling following operant reinforcement reveals distinct network activity patterns between contingent and noncontingent groups, supporting distinct neural mechanisms in appetitive or reactive aggression. We further identify high Fos activity in nucleus accumbens (NAc) in both contingent and noncontingent groups. NAc activity and changes in NAc neuroligin-2 (NLGN2) expression are associated with aggressive behavior. We find that the number of attack bouts is negatively correlated with NAc NLGN2 immunolabeling, regardless of contingent or noncontingent intruder presentation. As a result, molecularly dissociable features do not necessarily reflect operant behavioral repertoires.
2025
ACTIVITY-DEPENDENT CAPTURE REVEALS BRAIN-WIDE SIGNATURES OF ISOFLURANE ANESTHESIA-INDUCED UNCONSCIOUSNESS.
bioRxiv. 2025 Dec 5:2025.12.02.691631. doi: 10.64898/2025.12.02.691631 [PREPRINT] [FULL DOWNLOAD]
Background: General anesthesia is commonly used to produce unconsciousness across species, though the underlying neural substrates remain poorly understood. Here we test the hypothesis that isoflurane anesthesia produces unconsciousness by targeting discrete cell types and neural circuits distributed brain-wide, rather than by brain-wide non-specific binding or binding exclusively within single brain regions. Methods: We take advantage of a transgenic mouse system that expresses chemogenetic designer receptors exclusively activated by a designer drug (DREADDs) in an inducible Cre-dependent manner driven by Fos immediate early gene expression. Since Fos peaks with metabolic activity, we use this system to insert DREADDs brain-wide into neurons that are active under isoflurane anesthesia. We then test the effects of chemogenetic manipulation of brain-wide anesthesia-activated neural ensembles on behavior, in the absence of isoflurane. Results: Using iDisco+ intact brain clearing and light sheet microscopy, we describe brain-wide expression of the captured neurons revealing sparse, heterogeneous and spatially distributed cells. We quantify dense labeling across mesolimbic pathways that include the amygdala, hypothalamus, thalamus, and hindbrain nuclei, implicating these regions as candidate mediators of the anesthetic state. Chemogenetic manipulation of the brain-wide activated neural ensembles reproduces key components of anesthesia, including immobility and thermal anti-nociception. We observe significantly increased isoflurane sensitivity, though not a complete loss of consciousness as measured by the righting reflex, suggesting alternative mechanisms contribute to unconsciousness that are not captured by specific neural signatures. Conclusions: We provide causal evidence that isoflurane anesthesia engages discrete, distributed brain-wide circuitry, recapitulating dissociable components of general anesthesia.
HIERARCHICAL AND SPATIAL MAPPING OF WHOLE-BRAIN C-FOS ACTIVITY REVEALS DISTINCT OPIOID AND WITHDRAWAL NEURONAL ENSEMBLES.
bioRxiv. 2025 Sep 21:2025.09.21.677198. doi: 10.1101/2025.09.21.677198 [PREPRINT] [FULL DOWNLOAD]
How opioid exposure and withdrawal states shape brain activity at the systems and circuit level remains poorly understood. Here, we use whole-brain, cellular-resolution c-Fos mapping to define brain-wide activity patterns and neuronal ensembles associated with morphine administration and withdrawal. To account for the brain's anatomically nested structure, we developed and applied a hierarchical statistical framework that detects region-specific changes in activity and outperforms conventional methods that treat brain regions as individual, unrelated units. These distributed signals formed ensembles with consistent and anatomically structured patterns of activity, both within subregions and across multiple connected brain areas. By combining TRAP2-based activity tagging with acute whole-brain c-Fos staining, we identified morphine- and withdrawal-activated ensembles and found that they are largely non-overlapping at the single-cell level, even within the same brain region. Integration with existing spatial transcriptomics datasets identified molecular markers for these state-specific ensembles in key brain areas such as the nucleus accumbens, amygdala and ventral tegmental area. Lastly, by integrating Allen mouse whole-brain transcriptional datasets, we identified the molecular identity of the morphine-administration and withdrawal ensembles. These findings define dissociable neuronal ensembles that encode opposing drug states and introduce a scalable framework for linking whole-brain activity to molecular and circuit-level mechanisms.
BEHAVIORAL NEUROSCIENCE: DOMINANCE IN THE ABSENCE OF COMPETITION.
Curr Biol. 2025 Jul 21;35(14):R706-R708. doi: 10.1016/j.cub.2025.05.058 [FULL DOWNLOAD]
Mice infer dominance rank using chemosensory cues rather than physical competition. This sensory-based inference reshapes how we think about hierarchy learning, stability, and behavioral flexibility in social animals.
OPIOID-DRIVEN DISRUPTION OF THE SEPTUM REVEALS A ROLE FOR NEUROTENSIN-EXPRESSING NEURONS IN WITHDRAWAL.
Neuron. 2025 May 14:S0896-6273(25)00307-1. doi: 10.1016/j.neuron.2025.04.024 [FULL DOWNLOAD]
Opioid withdrawal is an intensively aversive experience and often drives relapse. The lateral septum (LS) is a forebrain structure that is important in aversion processing and has been linked to substance use disorders, but which LS cell types contribute to the maladaptive state of withdrawal is unknown. We used single-nucleus RNA sequencing to interrogate cell-type-specific gene expression changes induced by chronic morphine exposure and discovered that morphine globally disrupts LS cell types, but neurotensin-expressing neurons (LS-Nts) are selectively activated by naloxone. Using two-photon calcium imaging and ex vivo electrophysiology, we next demonstrate that LS-Nts neurons receive elevated glutamatergic drive in morphine-dependent mice and remain hyperactivated during withdrawal. Finally, we show that manipulating LS-Nts neurons during opioid withdrawal regulates pain coping and sociability. Together, these results suggest that LS-Nts neurons are a key neural substrate involved in opioid withdrawal and establish the LS as a crucial regulator of adaptive behaviors.
HETEROGENEOUS PERICOERULEAR NEURONS TUNE AROUSAL AND EXPLORATORY BEHAVIOURS.
Nature. 2025 May 7. doi: 10.1038/s41586-025-08952-w [FULL DOWNLOAD]
As the primary source of noradrenaline in the brain, the locus coeruleus (LC) regulates arousal, avoidance and stress responses1,2. However, how local neuromodulatory inputs control LC function remains unresolved. Here we identify a population of transcriptionally, spatially and functionally diverse GABAergic (γ-aminobutyric acid-producing) neurons in the LC dendritic field that receive distant inputs and modulate modes of LC firing to control global arousal levels and arousal-related processing and behaviours. We define peri-LC anatomy using viral tracing and combine single-cell RNA sequencing with spatial transcriptomics to molecularly define both LC noradrenaline-producing and peri-LC cell types. We identify several neuronal cell types that underlie peri-LC functional diversity using a series of complementary neural circuit approaches in behaving mice. Our findings indicate that LC and peri-LC neurons are transcriptionally, functionally and anatomically heterogenous neuronal populations that modulate arousal and avoidance states. Defining the molecular, cellular and functional diversity of the LC and peri-LC provides a roadmap for understanding the neurobiological basis of arousal, motivation and neuropsychiatric disorders.
POST-EJACULATORY INHIBITION OF FEMALE SEXUAL DRIVE VIA HETEROGENEOUS NEURONAL ENSEMBLES IN THE MEDIAL PREOPTIC AREA.
eLife. 2025 12:RP91765. doi: 10.7554/eLife.91765.3 [FULL DOWNLOAD]
EDITORIAL: SPANNING THE SPECTRUM OF SOCIAL BEHAVIOR: TOWARDS MORE TRANSLATIONALLY RELEVANT ANIMAL MODELS.
Psychopharmacology (Berl). 2025 May;242(5):885-887. doi: 10.1007/s00213-025-06755-5 [FULL DOWNLOAD]
Our mechanistic understanding of neuropsychiatric disorders is primarily based on preclinical studies using animal models (Shemesh and Chen 2023). However, despite the emergence of powerful new technologies, the translation and development of effective therapeutic treatments from these models and direct improvements to health outcomes has been slow (Venniro et al. 2020). We believe this impasse is partly due to limitations in animal models, particularly the omission of key social factors, which play a major role in the etiology of human psychiatric disorders (Heilig et al. 2016). Social factors encompass ethologically complex behaviors ranging from positive affiliative social interactions to agitation and aggression. Both affiliative and aggressive interactions can be rewarding for humans and laboratory animals. Recently, efforts to enhance the translational relevance of rodent models have increasingly incorporated these behaviors to better understand their effects on neuropsychiatric disorders and their underlying neural mechanisms (Golden et al. 2017; Navarrete et al. 2024; Ramsey et al. 2022; Venniro et al. 2018). Building on these directions, we organized a workshop for the European Behavioral Pharmacology Society (EBPS) to bridge the gap between researchers studying social factors and behavioral neuroscientists investigating neuropsychiatric disorders. The workshop aimed to create a collaborative forum focused on leveraging translationally relevant models of social behavior to investigate neuropsychiatric disorders. By doing so, we sought to facilitate future collaborations that use social behavior to bridge the translational gap between preclinical models and their clinical counterparts, improving strategies for identifying novel therapeutic targets for effective treatment of neuropsychiatric disorders.
BRAINWIDE GENETIC CAPTURE FOR CONSCIOUS STATE TRANSITIONS.
bioRxiv. 2025 Apr 3:2025.03.28.646066. doi: 10.1101/2025.03.28.646066 [PREPRINT] [FULL DOWNLOAD]
Spatially integrated mechanisms of consciousness are unclear. An approach to manipulate brainwide circuits regulating consciousness via synthetic central nervous system activation may pave the way for more precise transitions in consciousness and reveal underlying mechanisms. Toward this goal, we leverage anesthesia as a tool to probe consciousness at cellular resolution within the intact network. We perform brainwide chemogenetic capture of isoflurane anesthesia-activated circuitry in mice, in parallel with electrocorticography, wireless mechano-acoustic recording of peripheral physiology, and behavioral classification, to describe a synthetic state of altered consciousness generated in the absence of an anesthetic agent. We define patterns of activation under isoflurane using intact brain immediate early gene mapping combined with brainwide high density silicon probe recordings. Our data identify subcortical hotspots of neural activity in an unconsciousness network that is globally characterized by increased functional connectivity driven by select nodes. We provide technical resources spanning brainwide single-cell resolution maps and neurophysiologic datasets of the isoflurane-rendered unconscious state, along with an approach to further probe its global cellular-level mechanisms. Together, we present the foundation for future research to refine this viral-genetic brainwide approach to generate synthetic conscious state transitions, such as sleep, stasis, analgesia or anesthesia.
2024
DISTINCT DYNAMICS AND INTRINSIC PROPERTIES IN VENTRAL TEGMENTAL AREA POPULATIONS MEDIATE REWARD ASSOCIATION AND MOTIVATION.
Cell Rep. 2024 Aug 27;43(9):114668. doi: 10.1016/j.celrep.2024.114668 [FULL DOWNLOAD]
Ventral tegmental area (VTA) dopamine neurons regulate reward-related associative learning and reward-driven motivated behaviors, but how these processes are coordinated by distinct VTA neuronal subpopulations remains unresolved. Here, we compare the contribution of two primarily dopaminergic and largely non-overlapping VTA subpopulations, all VTA dopamine neurons and VTA GABAergic neurons of the mouse midbrain, to these processes. We find that the dopamine subpopulation that projects to the nucleus accumbens (NAc) core preferentially encodes reward-predictive cues and prediction errors. In contrast, the subpopulation that projects to the NAc shell preferentially encodes goal-directed actions and relative reward anticipation. VTA GABA neuron activity strongly contrasts VTA dopamine population activity and preferentially encodes reward outcome and retrieval. Electrophysiology, targeted optogenetics, and whole-brain input mapping reveal multiple convergent sources that contribute to the heterogeneity among VTA dopamine subpopulations that likely underlies their distinct encoding of reward-related associations and motivation that defines their functions in these contexts.
KEEPING IT SIMPLE – A SIMPLE BEHAVIORAL ANALYSIS (SIMBA) PRIMER.
NPP—Digital Psychiatry and Neuroscience 2, 13 (2024). doi: 10.1038/s44277-024-00014-9 [FULL DOWNLOAD]
Goodwin NL, Golden SA. Neuroscience is approaching a critical juncture, transitioning from subjective behavioral observation to objective behavioral definition. This is now possible due to analytical tools using machine-guided solutions for animal markerless key-point pose tracking (see Table 1 for specialized terminology definitions) and behavioral detection. However, it is often challenging for behaviorists to adopt these approaches due to a lack of specialized computational knowledge. We and others have spent significant effort to solve this problem by democratizing access to these approaches, making them accessible to non-specialists. However, as these tools increase access to machine learning approaches, an emerging problem is ensuring that the predictions algorithms are making and the biology that they are defining are explainable and understandable. To address these challenges, we have introduced Simple Behavioral Analysis (SimBA) as an open-source, supervised machine learning based platform for the automated detection of behavior, with a focus on understanding how the underlying machine learning algorithms make their decisions.
AN ARGININE-RICH NUCLEAR LOCALIZATION SIGNAL (ARGINLS) STRATEGY FOR STREAMLINED IMAGE SEGMENTATION OF SINGLE CELLS.
Proc Natl Acad Sci U S A. 2024 Aug 6;121(32):e2320250121. doi: 10.1073/pnas.2320250121 [FULL DOWNLOAD]
Szelenyi ER, Navarrete JS, Murry AD, Zhang Y, Girven KS, Kuo L, Cline MM, Bernstein MX, Burdyniuk M, Bowler B, Goodwin NL, Juarez B, Zweifel LS, Golden SA. High-throughput volumetric fluorescent microscopy pipelines can spatially integrate whole-brain structure and function at the foundational level of single cells. However, conventional fluorescent protein (FP) modifications used to discriminate single cells possess limited efficacy or are detrimental to cellular health. Here, we introduce a synthetic and nondeleterious nuclear localization signal (NLS) tag strategy, called “Arginine-rich NLS” (ArgiNLS), that optimizes genetic labeling and downstream image segmentation of single cells by restricting FP localization near-exclusively in the nucleus through a poly-arginine mechanism. A single N-terminal ArgiNLS tag provides modular nuclear restriction consistently across spectrally separate FP variants. ArgiNLS performance in vivo displays functional conservation across major cortical cell classes and in response to both local and systemic brain-wide AAV administration. Crucially, the high signal-to-noise ratio afforded by ArgiNLS enhances machine learning-automated segmentation of single cells due to rapid classifier training and enrichment of labeled cell detection within 2D brain sections or 3D volumetric whole-brain image datasets, derived from both staining-amplified and native signal. This genetic strategy provides a simple and flexible basis for precise image segmentation of genetically labeled single cells at scale and paired with behavioral procedures.
SIMPLE BEHAVIORAL ANALYSIS (SIMBA) AS A PLATFORM FOR EXPLAINABLE MACHINE LEARNING IN BEHAVIORAL NEUROSCIENCE.
Nature Neuroscience. 2024 May 22. doi: 10.1038/s41593-024-01649-9 [FULL DOWNLOAD]
Goodwin NL, Choong JJ, Hwang S, Pitts K, Bloom L, Islam A, Zhang YY, Szelenyi ER, Tong X, Newman EL, Miczek K, Wright HR, McLaughlin RJ, Norville ZC, Eshel N, Heshmati M, Nilsson SRO*, Golden SA*. The study of complex behaviors is often challenging when using manual annotation due to the absence of quantifiable behavioral definitions and the subjective nature of behavioral annotation. Integration of supervised machine learning approaches mitigates some of these issues through the inclusion of accessible and explainable model interpretation. To decrease barriers to access, and with an emphasis on accessible model explainability, we developed the open-source Simple Behavioral Analysis (SimBA) platform for behavioral neuroscientists. SimBA introduces several machine learning interpretability tools, including SHapley Additive exPlanation (SHAP) scores, that aid in creating explainable and transparent behavioral classifiers. Here we show how the addition of explainability metrics allows for quantifiable comparisons of aggressive social behavior across research groups and species, reconceptualizing behavior as a sharable reagent and providing an open-source framework. We provide an open-source, graphical user interface (GUI)-driven, well-documented package to facilitate the movement toward improved automation and sharing of behavioral classification tools across laboratories.
AN IMPLANTABLE DEVICE FOR WIRELESS MONITORING OF DIVERSE PHYSIO-BEHAVIORAL CHARACTERISTICS IN FREELY BEHAVING SMALL ANIMALS AND INTERACTING GROUPS.
Neuron. 2024 Jun 5;112(11):1764-1777.e5. doi: 10.1016/j.neuron.2024.02.020 [FULL DOWNLOAD]
Ouyang W, Kilner KJ, Xavier RMP, Liu Y, Lu Y, Feller SM, Pitts KM, Wu M, Ausra J, Jones I, Wu Y, Luan H, Trueb J, Higbee-Dempsey EM, Stepien I, Ghoreishi-Haack N, Haney CR, Li H, Kozorovitskiy Y, Heshmati M, Banks AR, Golden SA*, Good CH*, Rogers JA*. Comprehensive, continuous quantitative monitoring of intricately orchestrated physiological processes and behavioral states in living organisms can yield essential data for elucidating the function of neural circuits under healthy and diseased conditions, for defining the effects of potential drugs and treatments, and for tracking disease progression and recovery. Here, we report a wireless, battery-free implantable device and a set of associated algorithms that enable continuous, multiparametric physio-behavioral monitoring in freely behaving small animals and interacting groups. Through advanced analytics approaches applied to mechano-acoustic signals of diverse body processes, the device yields heart rate, respiratory rate, physical activity, temperature, and behavioral states. Demonstrations in pharmacological, locomotor, and acute and social stress tests and in optogenetic studies offer unique insights into the coordination of physio-behavioral characteristics associated with healthy and perturbed states. This technology has broad utility in neuroscience, physiology, behavior, and other areas that rely on studies of freely moving, small animal models.
2023
ASCL1 INDUCES NEUROGENESIS IN HUMAN MÜLLER GLIA.
Stem Cell Reports. 2023 Dec 12;18(12):2400-2417. doi: 10.1016/j.stemcr.2023.10.021 [FULL DOWNLOAD]
Wohlschlegel J, Finkbeiner C, Hoffer D, Kierney F, Prieve A, Murry AD, Haugan AK, Ortuño-Lizarán I, Rieke F, Golden SA, Reh TA. In mammals, loss of retinal cells due to disease or trauma is an irreversible process that can lead to blindness. Interestingly, regeneration of retinal neurons is a well established process in some non-mammalian vertebrates and is driven by the Müller glia (MG), which are able to re-enter the cell cycle and reprogram into neurogenic progenitors upon retinal injury or disease. Progress has been made to restore this mechanism in mammals to promote retinal regeneration: MG can be stimulated to generate new neurons in vivo in the adult mouse retina after the over-expression of the pro-neural transcription factor Ascl1. In this study, we applied the same strategy to reprogram human MG derived from fetal retina and retinal organoids into neurons. Combining single cell RNA sequencing, single cell ATAC sequencing, immunofluorescence, and electrophysiology we demonstrate that human MG can be reprogrammed into neurogenic cells in vitro.
POST-MATING INHIBITION OF FEMALE SEXUAL DRIVE VIA HETEROGENEOUS NEURONAL ENSEMBLES IN THE MEDIAL PREOPTIC AREA.
eLife. 2023 Nov 14; eLife12:RP91765. [FULL DOWNLOAD]
LATERAL LINE ABLATION BY OTOTOXIC COMPOUNDS RESULTS IN DISTINCT RHEOTAXIS PROFILES IN LARVAL ZEBRAFISH.
Commun Biol. 2023 Jan 21;6(1):84. doi: 10.1038/s42003-023-04449-2 [FULL DOWNLOAD]
Newton KC, Kacev D, Nilsson SRO, Saettele AL, Golden SA, Sheets L. The zebrafish lateral line is an established model for hair cell organ damage, yet few studies link mechanistic disruptions to changes in biologically relevant behavior. We used larval zebrafish to determine how damage via ototoxic compounds impact rheotaxis. Larvae were treated with CuSO4 or neomycin to disrupt lateral line function then exposed to water flow stimuli. Their swimming behavior was recorded on video then DeepLabCut and SimBA software were used to track movements and classify rheotaxis behavior, respectively. Lateral line-disrupted fish performed rheotaxis, but they swam greater distances, for shorter durations, and with greater angular variance than controls. Furthermore, spectral decomposition analyses confirmed that lesioned fish exhibited ototoxic compound-specific behavioral profiles with distinct changes in the magnitude, frequency, and cross-correlation between fluctuations in linear and angular movements. Our observations demonstrate that lateral line input is needed for fish to hold their station in flow efficiently and reveals that commonly used lesion methods have unique effects on rheotaxis behavior.
2022
INCUBATION OF PALATABLE FOOD CRAVING IS ASSOCIATED WITH BRAIN-WIDE NEURONAL ACTIVATION IN MICE.
Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2209382119. doi: 10.1073/pnas.2209382119 [FULL DOWNLOAD]
Madangopal R, Szelenyi ER, Nguyen J, Brenner MB, Drake OR, Pham DQ, Shekara A, Jin M, Choong JJ, Heins C, Komer LE, Weber SJ, Hope BT, Shaham Y, Golden SA. Studies using rodent models have shown that relapse to drug or food seeking increases progressively during abstinence, a behavioral phenomenon termed "incubation of craving." Mechanistic studies of incubation of craving have focused on specific neurobiological targets within preselected brain areas. Recent methodological advances in whole-brain immunohistochemistry, clearing, and imaging now allow unbiased brain-wide cellular resolution mapping of regions and circuits engaged during learned behaviors. However, these whole-brain imaging approaches were developed for mouse brains, while incubation of drug craving has primarily been studied in rats, and incubation of food craving has not been demonstrated in mice. Here, we established a mouse model of incubation of palatable food craving and examined food reward seeking after 1, 15, and 60 abstinence days. We then used the neuronal activity marker Fos with intact-brain mapping procedures to identify corresponding patterns of brain-wide activation. Relapse to food seeking was significantly higher after 60 abstinence days than after 1 or 15 days. Using unbiased ClearMap analysis, we identified increased activation of multiple brain regions, particularly corticostriatal structures, following 60 but not 1 or 15 abstinence days. We used orthogonal SMART2 analysis to confirm these findings within corticostriatal and thalamocortical subvolumes and applied expert-guided registration to investigate subdivision and layer-specific activation patterns. Overall, we 1) identified brain-wide activity patterns during incubation of food seeking using complementary analytical approaches and 2) provide a single-cell resolution whole-brain atlas that can be used to identify functional networks and global architecture underlying the incubation of food craving.
SEX DIFFERENCES IN APPETITIVE AND REACTIVE AGGRESSION.
Neuropsychopharmacology. 2022 Sep;47(10):1746-1754. doi: 10.1038/s41386-022-01375-5 [FULL DOWNLOAD]
Aubry AV, Joseph Burnett C, Goodwin NL, Li L, Navarrete J, Zhang Y, Tsai V, Durand-de Cuttoli R, Golden SA*, Russo SJ Aggression is an evolutionarily conserved, adaptive component of social behavior. Studies in male mice illustrate that aggression is influenced by numerous factors including the degree to which an individual finds aggression rewarding and will work for access to attack and subordinate mice. While such studies have expanded our understanding of the molecular and circuit mechanisms of male aggression very little is known about female aggression, within these established contexts. Here we use an ethologically relevant model of male vs. female aggression by pair housing adult male and female outbred CFW mice with opposite sex cage mates. We assess reactive (defensive) aggression in the resident intruder (RI) test and appetitive (rewarding) aggression in the aggression conditioned place preference (CPP) and operant self-administration (SA) tests. Our results show dramatic sex differences in both qualitative and quantitative aspects of reactive vs. appetitive aggression. Males exhibit more wrestling and less investigative behavior during RI, find aggression rewarding, and will work for access to a subordinate to attack. Females exhibit more bites, alternate between aggressive behaviors and investigative behaviors more readily during RI, however, they do not find aggression to be rewarding or reinforcing. These results establish sex differences in aggression in mice, providing an important resource for the field to better understand the circuit and molecular mechanisms of aggression in both sexes.
TOWARD THE EXPLAINABILITY, TRANSPARENCY, AND UNIVERSALITY OF MACHINE LEARNING FOR BEHAVIORAL CLASSIFICATION IN NEUROSCIENCE.
Curr Opin Neurobiol. 2022 Apr;73:102544. doi: 10.1016/j.conb.2022.102544 [FULL DOWNLOAD]
Goodwin NL, Nilsson SRO, Choong JJ, Golden SA. The use of rigorous ethological observation via machine learning techniques to understand brain function (computational neuroethology) is a rapidly growing approach that is poised to significantly change how behavioral neuroscience is commonly performed. With the development of open-source platforms for automated tracking and behavioral recognition, these approaches are now accessible to a wide array of neuroscientists despite variations in budget and computational experience. Importantly, this adoption has moved the field toward a common understanding of behavior and brain function through the removal of manual bias and the identification of previously unknown behavioral repertoires. Although less apparent, another consequence of this movement is the introduction of analytical tools that increase the explainabilty, transparency, and universality of the machine-based behavioral classifications both within and between research groups. Here, we focus on three main applications of such machine model explainabilty tools and metrics in the drive toward behavioral (i) standardization, (ii) specialization, and (iii) explainability. We provide a perspective on the use of explainability tools in computational neuroethology, and detail why this is a necessary next step in the expansion of the field. Specifically, as a possible solution in behavioral neuroscience, we propose the use of Shapley values via Shapley Additive Explanations (SHAP) as a diagnostic resource toward explainability of human annotation, as well as supervised and unsupervised behavioral machine learning analysis.
SMART: AN OPEN-SOURCE EXTENSION OF WHOLEBRAIN FOR INTACT MOUSE BRAIN REGISTRATION AND SEGMENTATION.
eNeuro. 2022 May 3;9(3):ENEURO.0482-21.2022. doi: 10.1523/ENEURO.0482-21.2022 [FULL DOWNLOAD]
Jin M, Nguyen JD, Weber SJ, Mejias-Aponte CA, Madangopal R, Golden SA. Mapping immediate early gene (IEG) expression across intact mouse brains allows for unbiased identification of brain-wide activity patterns underlying complex behaviors. Accurate registration of sample brains to a common anatomic reference is critical for precise assignment of IEG-positive ("active") neurons to known brain regions of interest (ROIs). While existing automated voxel-based registration methods provide a high-throughput solution, they require substantial computing power, can be difficult to implement and fail when brains are damaged or only partially imaged. Additionally, it is challenging to cross-validate these approaches or compare them to any preexisting literature based on serial coronal sectioning. Here, we present the open-source R package SMART (Semi-Manual Alignment to Reference Templates) that extends the WholeBrain R package framework to automated segmentation and semi-automated registration of intact mouse brain light-sheet fluorescence microscopy (LSFM) datasets. The SMART package was created for novice programmers and introduces a streamlined pipeline for aligning, registering, and segmenting LSFM volumetric datasets across the anterior-posterior (AP) axis, using a simple "choice game" and interactive menus. SMART provides the flexibility to register whole brains, partial brains or discrete user-chosen images, and is fully compatible with traditional sectioned coronal slice-based analyses. We demonstrate SMART's core functions using example datasets and provide step-by-step video tutorials for installation and implementation of the package. We also present a modified iDISCO+ tissue clearing procedure for uniform immunohistochemical labeling of the activity marker Fos across intact mouse brains. The SMART pipeline, in conjunction with the modified iDISCO+ Fos procedure, is ideally suited for examination and orthogonal cross-validation of brain-wide neuronal activation datasets.
THE ROLE OF THE LATERAL HABENULA IN SUICIDE: A CALL FOR FURTHER EXPLORATION.
Front Behav Neurosci. 2022 Mar 14;16:812952. doi: 10.3389/fnbeh.2022.812952 [FULL DOWNLOAD]
Marks RB, Wee JY, Jacobson SV, Hashimoto K, O'Connell KL, Golden SA, Baker PM, Law KC Despite decades of significant effort in research, policy, and prevention, suicide rates have continued to rise to the current peak of 14.6 per 100,000 deaths. This has resulted in a concerted effort to identify biomarkers associated with suicidal behavior in the brain, to provide predictions that are better than the chance of discerning who will die by suicide. We propose that the lateral habenula (LHb), and its dysfunction during a suicidal crisis, is a critical component of the transition from suicidal ideations to self-harm. Moreover, the LHb-a key functional node in brain reward circuitry-has not been ascribed a contributory role in suicidal behavior. We argue that the LHb anchors a "suicide circuit" and call for suicide researchers to directly examine the role of the LHb, and its long-term modulation, in response to the negative affect in suicidal behavior. Discerning the neural mechanisms of this contribution will require the collaboration of neuroscientists and psychologists. Consequently, we highlight and discuss research on LHb as it relates to suicidal ideation, suicidal behavior, or death by suicide. In so doing we hope to address the bench-to-bedside translational issues currently involved in suicide research and suggest a developmental framework that focuses on specific structures motivated by theoretical anchors as a way to incorporate neurobiological findings within the context of clinical theory.
AUTOMATED PROCEDURE TO ASSESS PUP RETRIEVAL IN LABORATORY MICE.
Sci Rep. 2022 Jan 31;12(1):1663. doi: 10.1038/s41598-022-05641-w [FULL DOWNLOAD]
Winters C, Gorssen W, Ossorio-Salazar VA, Nilsson S, Golden S, D'Hooge R. Despite decades of significant effort in research, policy, and prevention, suicide rates have continued to rise to the current peak of 14.6 per 100,000 deaths. This has resulted in a concerted effort to identify biomarkers associated with suicidal behavior in the brain, to provide predictions that are better than the chance of discerning who will die by suicide. We propose that the lateral habenula (LHb), and its dysfunction during a suicidal crisis, is a critical component of the transition from suicidal ideations to self-harm. Moreover, the LHb-a key functional node in brain reward circuitry-has not been ascribed a contributory role in suicidal behavior. We argue that the LHb anchors a "suicide circuit" and call for suicide researchers to directly examine the role of the LHb, and its long-term modulation, in response to the negative affect in suicidal behavior. Discerning the neural mechanisms of this contribution will require the collaboration of neuroscientists and psychologists. Consequently, we highlight and discuss research on LHb as it relates to suicidal ideation, suicidal behavior, or death by suicide. In so doing we hope to address the bench-to-bedside translational issues currently involved in suicide research and suggest a developmental framework that focuses on specific structures motivated by theoretical anchors as a way to incorporate neurobiological findings within the context of clinical theory.
2021
SOCIAL MICE SEEKING CIRCUITS.
Nature Neuroscience. 2021 Jun;24(6):761-762. doi: 10.1038/s41593-021-00861-1 [FULL DOWNLOAD]
Szelenyi ER, Goodwin NL, Golden SA. Hu et al. show that the posterodorsal medial amygdala selectively controls social-reward seeking through its intersection with canonical dopaminergic reward circuits. To identify this circuitry, the authors developed an elegant new affiliative social operant procedure that separates social interaction from social-reward seeking.
QUANTITATIVE STANDARDIZATION OF RESIDENT MOUSE BEHAVIOR FOR STUDIES OF AGGRESSION AND SOCIAL DEFEAT.
Neuropsychopharmacology. 2021 Aug;46(9):1584-1593. doi: 10.1038/s41386-021-01018-1 [FULL DOWNLOAD]
Kwiatkowski CC, Akaeze H, Ndlebe I, Goodwin N, Eagle AL, Moon K, Bender AR, Golden SA, Robison AJ. Territorial reactive aggression in mice is used to study the biology of aggression-related behavior and is also a critical component of procedures used to study mood disorders, such as chronic social defeat stress. However, quantifying mouse aggression in a systematic, representative, and easily adoptable way that allows direct comparison between cohorts within or between studies remains a challenge. Here, we propose a structural equation modeling approach to quantify aggression observed during the resident-intruder procedure. Using data for 658 sexually experienced CD-1 male mice generated by three research groups across three institutions over a 10-year period, we developed a higher-order confirmatory factor model wherein the combined contributions of latency to the first attack, number of attack bouts, and average attack duration on each trial day (easily observable metrics that require no specialized equipment) are used to quantify individual differences in aggression. We call our final model the Mouse Aggression Detector (MAD) model. Correlation analyses between MAD model factors estimated from multiple large datasets demonstrate generalizability of this measurement approach, and we further establish the stability of aggression scores across time within cohorts and demonstrate the utility of MAD for selecting aggressors which will generate a susceptible phenotype in social defeat experiments. Thus, this novel aggression scoring technique offers a systematic, high-throughput approach for aggressor selection in chronic social defeat stress studies and a more consistent and accurate study of mouse aggression itself.
REGULATION OF IMPULSIVE AND AGGRESSIVE BEHAVIOURS BY A NOVEL LNCRNA.
Mol Psychiatry. 2021 Aug;26(8):3751-3764. doi: 10.1038/s41380-019-0637-4 [FULL DOWNLOAD]
Labonté B, Abdallah K, Maussion G, Yerko V, Yang J, Bittar T, Quessy F, Golden SA, Navarro L, Checknita D, Gigek C, Lopez JP, Neve RL, Russo SJ, Tremblay RE, Côté G, Meaney MJ, Mechawar N, Nestler EJ, Turecki G. High impulsive and aggressive traits associate with poor behavioural self-control. Despite their importance in predicting behavioural negative outcomes including suicide, the molecular mechanisms underlying the expression of impulsive and aggressive traits remain poorly understood. Here, we identified and characterized a novel long noncoding RNA (lncRNA), acting as a regulator of the monoamine oxidase A (MAOA) gene in the brain, and named it MAOA-associated lncRNA (MAALIN). Our results show that in the brain of suicide completers, MAALIN is regulated by a combination of epigenetic mechanisms including DNA methylation and chromatin modifications. Elevated MAALIN in the dentate gyrus of impulsive-aggressive suicides was associated with lower MAOA expression. Viral overexpression of MAALIN in neuroprogenitor cells decreased MAOA expression while CRISPR-mediated knock out resulted in elevated MAOA expression. Using viral-mediated gene transfer, we confirmed that MAALIN in the hippocampus significantly decreases MAOA expression and exacerbates the expression of impulsive-aggressive behavioural traits in CD1 aggressive mice. Overall, our findings suggest that variations in DNA methylation mediate the differential expression of a novel lncRNA that acts on MAOA expression to regulate impulsive-aggressive behaviours.
2020
RAGE AGAINST THE MACHINE: ADVANCING THE STUDY OF AGGRESSION ETHOLOGY VIA MACHINE LEARNING.
Psychopharmacology (Berl). 2020 Sep;237(9):2569-2588. doi: 10.1007/s00213-020-05577-x [FULL DOWNLOAD]
Goodwin NL, Nilsson SRO, Golden SA. Rationale: Aggression, comorbid with neuropsychiatric disorders, exhibits with diverse clinical presentations and places a significant burden on patients, caregivers, and society. This diversity is observed because aggression is a complex behavior that can be ethologically demarcated as either appetitive (rewarding) or reactive (defensive), each with its own behavioral characteristics, functionality, and neural basis that may transition from adaptive to maladaptive depending on genetic and environmental factors. There has been a recent surge in the development of preclinical animal models for studying appetitive aggression-related behaviors and identifying the neural mechanisms guiding their progression and expression. However, adoption of these procedures is often impeded by the arduous task of manually scoring complex social interactions. Manual observations are generally susceptible to observer drift, long analysis times, and poor inter-rater reliability, and are further incompatible with the sampling frequencies required of modern neuroscience methods. Objectives: In this review, we discuss recent advances in the preclinical study of appetitive aggression in mice, paired with our perspective on the potential for machine learning techniques in producing automated, robust scoring of aggressive social behavior. We discuss critical considerations for implementing valid computer classifications within behavioral pharmacological studies. Key results: Open-source automated classification platforms can match or exceed the performance of human observers while removing the confounds of observer drift, bias, and inter-rater reliability. Furthermore, unsupervised approaches can identify previously uncharacterized aggression-related behavioral repertoires in model species. Discussion and conclusions: Advances in open-source computational approaches hold promise for overcoming current manual annotation caveats while also introducing and generalizing computational neuroethology to the greater behavioral neuroscience community. We propose that currently available open-source approaches are sufficient for overcoming the main limitations preventing wide adoption of machine learning within the context of preclinical aggression behavioral research.
DEPRESSION AND SOCIAL DEFEAT STRESS ARE ASSOCIATED WITH INHIBITORY SYNAPTIC CHANGES IN THE NUCLEUS ACCUMBENS.
J Neurosci. 2020 Aug 5;40(32):6228-6233. doi: 10.1523/JNEUROSCI.2568-19.2020 [FULL DOWNLOAD]
Heshmati M, Christoffel DJ, LeClair K, Cathomas F, Golden SA, Aleyasin H, Turecki G, Friedman AK, Han MH, Menard C, Russo SJ. Chronic stress in both humans and rodents induces a robust downregulation of neuroligin-2, a key component of the inhibitory synapse, in the NAc that modifies behavioral coping mechanisms and stress resiliency in mice. Here we extend this observation by examining the role of two other inhibitory synapse constituents, vesicular GABA transporter (vGAT) and gephyrin, in the NAc of male mice that underwent chronic social defeat stress (CSDS) and in patients with major depressive disorder (MDD). We first performed transcriptional profiling of vGAT and gephyrin in postmortem NAc samples from a cohort of healthy controls, medicated, and nonmedicated MDD patients. In parallel, we conducted whole-cell electrophysiology recordings in the NAc of stress-susceptible and stress-resilient male mice following 10 d of CSDS. Finally, we used immunohistochemistry to analyze protein levels of vGAT and gephyrin in the NAc of mice after CSDS. We found that decreased vGAT and gephyrin mRNA in the NAc of nonmedicated MDD patients is paralleled by decreased inhibitory synapse markers and decreased frequency of mini inhibitory postsynaptic currents (mIPSC) in the NAc of susceptible mice, indicating a reduction in the number of NAc inhibitory synapses that is correlated with depression-like behavior. Overall, these findings suggest a common state of reduced inhibitory tone in the NAc in depression and stress susceptibility.
OREXIN SIGNALING IN GABAERGIC LATERAL HABENULA NEURONS MODULATES AGGRESSIVE BEHAVIOR IN MALE MICE.
Nat Neurosci. 2020 May;23(5):638-650. doi: 10.1038/s41593-020-0617-7 [FULL DOWNLOAD]
Flanigan ME, Aleyasin H, Li L, Burnett CJ, Chan KL, LeClair KB, Lucas EK, Matikainen-Ankney B, Durand-de Cuttoli R, Takahashi A, Menard C, Pfau ML, Golden SA, Bouchard S, Calipari ES, Nestler EJ, DiLeone RJ, Yamanaka A, Huntley GW, Clem RL, Russo SJ. Heightened aggression is characteristic of multiple neuropsychiatric disorders and can have various negative effects on patients, their families and the public. Recent studies in humans and animals have implicated brain reward circuits in aggression and suggest that, in subsets of aggressive individuals, domination of subordinate social targets is reinforcing. In this study, we showed that, in male mice, orexin neurons in the lateral hypothalamus activated a small population of glutamic acid decarboxylase 2 (GAD2)-expressing neurons in the lateral habenula (LHb) via orexin receptor 2 (OxR2) and that activation of these GAD2 neurons promoted male-male aggression and conditioned place preference for aggression-paired contexts. Moreover, LHb GAD2 neurons were inhibitory within the LHb and dampened the activity of the LHb as a whole. These results suggest that the orexin system is important for the regulation of inter-male aggressive behavior and provide the first functional evidence of a local inhibitory circuit within the LHb.
MOLECULAR ADAPTATIONS OF THE BLOOD-BRAIN BARRIER PROMOTE STRESS RESILIENCE VS. DEPRESSION.
Proc Natl Acad Sci U S A. 2020 Feb 11;117(6):3326-3336. doi: 10.1073/pnas.1914655117 [FULL DOWNLOAD]
Dudek KA, Dion-Albert L, Lebel M, LeClair K, Labrecque S, Tuck E, Ferrer Perez C, Golden SA, Tamminga C, Turecki G, Mechawar N, Russo SJ, Menard C. Preclinical and clinical studies suggest that inflammation and vascular dysfunction contribute to the pathogenesis of major depressive disorder (MDD). Chronic social stress alters blood-brain barrier (BBB) integrity through loss of tight junction protein claudin-5 (cldn5) in male mice, promoting passage of circulating proinflammatory cytokines and depression-like behaviors. This effect is prominent within the nucleus accumbens, a brain region associated with mood regulation; however, the mechanisms involved are unclear. Moreover, compensatory responses leading to proper behavioral strategies and active resilience are unknown. Here we identify active molecular changes within the BBB associated with stress resilience that might serve a protective role for the neurovasculature. We also confirm the relevance of such changes to human depression and antidepressant treatment. We show that permissive epigenetic regulation of cldn5 expression and low endothelium expression of repressive cldn5-related transcription factor foxo1 are associated with stress resilience. Region- and endothelial cell-specific whole transcriptomic analyses revealed molecular signatures associated with stress vulnerability vs. resilience. We identified proinflammatory TNFα/NFκB signaling and hdac1 as mediators of stress susceptibility. Pharmacological inhibition of stress-induced increase in hdac1 activity rescued cldn5 expression in the NAc and promoted resilience. Importantly, we confirmed changes in HDAC1 expression in the NAc of depressed patients without antidepressant treatment in line with CLDN5 loss. Conversely, many of these deleterious CLDN5-related molecular changes were reduced in postmortem NAc from antidepressant-treated subjects. These findings reinforce the importance of considering stress-induced neurovascular pathology in depression and provide therapeutic targets to treat this mood disorder and promote resilience.
TAKING ACTION: EMPATHY AND SOCIAL INTERACTION IN RATS.
Neuropsychopharmacology. 2020 Jun;45(7):1081-1082. doi: 10.1038/s41386-019-0596-0 [FULL DOWNLOAD]
2019
ANIMAL MODELS OF (OR FOR) AGGRESSION REWARD, ADDICTION, AND RELAPSE: BEHAVIOR AND CIRCUITS.
The Journal of Neuroscience. 2019 May 22;39(21):3996-4008. doi: 10.1523/JNEUROSCI.0151-19.2019 [FULL DOWNLOAD]
NUCLEUS ACCUMBENS DRD1-EXPRESSING NEURONS CONTROL AGGRESSION SELF-ADMINISTRATION AND AGGRESSION SEEKING IN MICE.
The Journal of Neuroscience. 2019 Mar 27;39(13):2482-2496. doi: 10.1523/JNEUROSCI.2409-18.2019 [FULL DOWNLOAD]
2018
VOLITIONAL SOCIAL INTERACTION PREVENTS DRUG ADDICTION IN RAT MODELS.
Nature Neuroscience. 2018 Oct 15. doi: 10.1038/s41593-018-0246-6 [FULL DOWNLOAD]
CELL-TYPE-SPECIFIC ROLE OF ΔFOSB IN NUCLEUS ACCUMBENS IN MODULATING INTERMALE AGGRESSION.
J Neurosci. 2018 Jun 27;38(26):5913-5924. doi: 10.1523/JNEUROSCI.0296-18.2018 [FULL DOWNLOAD]
EPIGENETIC MODULATION OF INFLAMMATION AND SYNAPTIC PLASTICITY PROMOTES RESILIENCE AGAINST STRESS IN MICE.
Nat Commun. 2018 Feb 2;9(1):477. doi: 10.1038/s41467-017-02794-5 [FULL DOWNLOAD]
CELL-TYPE-SPECIFIC ROLE FOR NUCLEUS ACCUMBENS NEUROLIGIN-2 IN DEPRESSION AND STRESS SUSCEPTIBILITY.
Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):1111-1116. doi: 10.1073/pnas.1719014115 [FULL DOWNLOAD]
AGGRESSION ADDICTION AND RELAPSE: A NEW FRONTIER IN PSYCHIATRY.
Neuropsychopharmacology. 2018 Jan;43(1):224-225. doi: 10.1038/npp.2017.173 [FULL DOWNLOAD]
COMBINATORIAL PSYCHO-PHARMACOLOGICAL APPROACHES FOR THE TREATMENT OF ABNORMAL AGGRESSION.
Neuropsychopharmacology. 2018 Jan;43(2):233-234. doi: 10.1038/npp.2017.174 [FULL DOWNLOAD]
2017
DRP1 MITOCHONDRIAL FISSION IN D1 NEURONS MEDIATES BEHAVIORAL AND CELLULAR PLASTICITY DURING EARLY COCAINE ABSTINENCE.
Neuron. 2017 Dec 20;96(6):1327-1341.e6. doi: 10.1016/j.neuron.2017.11.037 [FULL DOWNLOAD]
SOCIAL STRESS INDUCES NEUROVASCULAR PATHOLOGY PROMOTING DEPRESSION.
Nat Neurosci. 2017 Dec;20(12):1752-1760. doi: 10.1038/s41593-017-0010-3 [FULL DOWNLOAD]
AN EMERGING ROLE FOR THE LATERAL HABENULA IN AGGRESSIVE BEHAVIOR.
Pharmacol Biochem Behav. 2017 Nov;162:79-86. doi: 10.1016/j.pbb.2017.05.003 [FULL DOWNLOAD]
COMPULSIVE ADDICTION-LIKE AGGRESSIVE BEHAVIOR IN MICE.
Biol Psychiatry. 2017 Aug 15;82(4):239-248. doi: 10.1016/j.biopsych.2017.03.004 [FULL DOWNLOAD]
PERSISTENT CONDITIONED PLACE PREFERENCE TO AGGRESSION EXPERIENCE IN ADULT MALE SEXUALLY-EXPERIENCED CD-1 MICE.
Genes Brain Behav. 2017 Jan;16(1):44-55. doi: 10.1111/gbb.12310 [FULL DOWNLOAD]
2016
INTEGRATIVE ANALYSIS OF SEX-SPECIFIC MICRORNA NETWORKS FOLLOWING STRESS IN MOUSE NUCLEUS ACCUMBENS.
Front Mol Neurosci. 2016 Dec 23;9:144. doi: 10.3389/fnmol.2016.00144 [FULL DOWNLOAD]
BASAL FOREBRAIN PROJECTIONS TO THE LATERAL HABENULA MODULATE AGGRESSION REWARD.
Nature. 2016 Jun 30;534(7609):688-92. doi: 10.1038/nature18601 [FULL DOWNLOAD]
MEFLOQUINE IN THE NUCLEUS ACCUMBENS PROMOTES SOCIAL AVOIDANCE AND ANXIETY-LIKE BEHAVIOR IN MICE.
Neuropharmacology. 2016 Feb;101:351-7. doi: 10.1016/j.neuropharm.2015.10.013 [FULL DOWNLOAD]
2015
SEX DIFFERENCES IN NUCLEUS ACCUMBENS TRANSCRIPTOME PROFILES ASSOCIATED WITH SUSCEPTIBILITY VERSUS RESILIENCE TO SUBCHRONIC VARIABLE STRESS.
J Neurosci. 2015 Dec 16;35(50):16362-76. doi: 10.1523/JNEUROSCI.1392-15.2015 [FULL DOWNLOAD]
ACF CHROMATIN-REMODELING COMPLEX MEDIATES STRESS-INDUCED DEPRESSIVE-LIKE BEHAVIOR.
Nat Med. 2015 Oct;21(10):1146-53. doi: 10.1038/nm.3939 [FULL DOWNLOAD]
EFFECTS OF ACUTE AND CHRONIC SOCIAL DEFEAT STRESS ARE DIFFERENTIALLY MEDIATED BY THE DYNORPHIN/KAPPA-OPIOID RECEPTOR SYSTEM.
Behav Pharmacol. 2015 Oct;26(7 Spec No):654-63. doi: 10.1097/FBP.0000000000000155 [FULL DOWNLOAD]
EXCITATORY TRANSMISSION AT THALAMO-STRIATAL SYNAPSES MEDIATES SUSCEPTIBILITY TO SOCIAL STRESS.
Nat Neurosci. 2015 Jul;18(7):962-4. doi: 10.1038/nn.4034 [FULL DOWNLOAD]
2014
LOCUS-SPECIFIC EPIGENETIC REMODELING CONTROLS ADDICTION- AND DEPRESSION-RELATED BEHAVIORS.
Nat Neurosci. 2014 Dec;17(12):1720-7. doi: 10.1038/nn.3871 [FULL DOWNLOAD]