About

Gregory Corder, Ph.D., is an Assistant Professor of Psychiatry in the Department of Psychiatry at the University of Pennsylvania's Perelman School of Medicine. His research focuses on deciphering the neural basis of pain perception, investigating how pathological changes in brain networks drive chronic pain and opioid dependence, and developing novel therapeutic strategies. His lab employs techniques such as in vivo calcium imaging, optogenetics, viral tool development, single-nuclei RNA sequencing, neuroanatomical tracing, and deep-learning behavior modeling to understand how brain circuits encode pain, pleasure, and affective states in preclinical rodent models. Dr. Corder's work aims to map the circuits and molecular mechanisms underlying the transition from acute to chronic pain, emphasizing pain as an emotionally charged state that influences cognition and behavior. A major focus of his research is opioid pharmacology and addiction-related plasticity, where his lab investigates non-opioid analgesic therapies, circuit-level mechanisms of opioid action, and gene therapies for chronic pain. His team has pioneered activity-dependent genetic tools for capturing pain-active neurons, developed next-generation circuit-based therapies, and identified new pathways for non-addictive pain relief. By integrating systems neuroscience, computational modeling, and translational pharmacology, his research bridges basic discovery with therapeutic innovation to develop more effective, non-addictive treatments for chronic pain and opioid dependence. Beyond his research, Dr. Corder is committed to mentoring the next generation of neuroscientists, with a strong record of trainee fellowships, interdisciplinary collaboration, and leadership in neuroscience training.

Research topics

• Machine Learning
• Computer Science
• Artificial Intelligence
• Psychology
• Medicine
• Neuroscience

Selected publications

• Top-down control of the descending pain modulatory system drives multimodal placebo analgesia

  Neuron · 2026-04-01

  articleOpen access

  Placebo analgesia, in which expectation and prior experience suppress pain in response to an inert treatment, is a powerful clinical phenomenon whose causal neural basis remains unclear. By reverse-translating a human placebo paradigm to mice, we identify neural circuits linking the cortex to the brainstem that causally mediate placebo pain relief. Placebo conditioning suppresses both nociceptive and affective-motivational pain behaviors and generalizes to unconditioned forms of pain. Descending neurons in the ventrolateral periaqueductal gray (vlPAG) are indispensable for both morphine and placebo analgesia, but the placebo effect additionally requires medial prefrontal and anterior cingulate cortical inputs to the vlPAG. Conditioning potentiates noxious stimulus-evoked endogenous opioid release in the vlPAG, which causally gates descending pain modulation. Remarkably, conditioning in pain-naive animals produces lasting placebo analgesia after injury. These findings identify a central circuit mechanism of placebo analgesia and suggest a translational strategy in which preventive placebo conditioning can build resilience to pain.

  PublisherDOI

• Red-Shifted Chemigenetic Glutamate Indicators for Recording Multiplexed Neural Computation

  SSRN Electronic Journal · 2026-01-01

  preprintOpen access
  PublisherDOI

• Heart rate and sleep history encode ultradian REM sleep timing

  Current Biology · 2026-03-01

  articleOpen access

  During sleep, the brain alternates between rapid eye movement (REM) and non-REM (NREM) sleep, with recurring REM sleep episodes forming the ultradian sleep cycle, a hallmark of mammalian sleep. However, the mechanisms regulating the ultradian timing of REM sleep remain elusive, underscoring the need for reliable physiological predictors. Here, we developed a machine learning framework to identify features in the electroencephalogram (EEG), electromyogram (EMG), and sleep history that predict the timing of REM sleep in mice. A bidirectional long short-term memory (BiLSTM) network, trained to classify sleep-wake states, embedded EEG and EMG signals into a low-dimensional latent space, revealing slow, ramping dynamics between consecutive REM sleep episodes. Using these latent EEG/EMG features together with preceding sleep history, we predicted the time until the next REM episode. Feature importance analysis identified heart rate in the EMG, combined with sleep history, as a key predictor of REM sleep timing. Under heightened homeostatic pressure for REM sleep, heart rate decayed faster and reached lower levels, whereas pharmacologically elevating heart rate reduced REM sleep. Our findings position heart rate as a physiological marker of REM sleep timing and suggest a close link between cardiovascular regulation and the mechanisms controlling the ultradian sleep cycle.

  PublisherOA PDFDOI

• Mimicking opioid analgesia in cortical pain circuits

  Nature · 2026-01-07 · 2 citations

  articleOpen accessSenior author

  The anterior cingulate cortex is a key brain region involved in the affective and motivational dimensions of pain, but how opioid analgesics modulate this cortical circuit remains unclear1. Uncovering how opioids alter nociceptive neural dynamics to produce pain relief is essential for developing safer and more targeted treatments for chronic pain. Here we show that a population of cingulate neurons encodes spontaneous pain-related behaviours and is selectively modulated by morphine. Using deep learning behavioural analyses combined with longitudinal neural recordings in mice, we identified a persistent shift in cortical activity patterns following nerve injury that reflects the emergence of an unpleasant, affective chronic pain state. Morphine reversed these neuropathic neural dynamics and reduced affective–motivational behaviours without altering sensory detection or reflexive responses, mirroring how opioids alleviate pain unpleasantness in humans. Leveraging these findings, we built a biologically inspired chemogenetic gene therapy that targets opioid-sensitive neurons in the cingulate using a synthetic μ-opioid receptor promoter to drive inhibition2. This opioid-mimetic chemogenetic gene therapy recapitulated the analgesic effects of morphine during chronic neuropathic pain, thereby offering a new strategy for precision pain management that targets a key nociceptive cortical opioid circuit with safe, on-demand analgesia. The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

  PublisherDOI

• Differential modulation of aversive signaling by expectation across the cingulate cortex

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-05

  articleOpen accessSenior authorCorresponding

  Abstract Pain-related aversion is an affective-motivational state driven by sensory experience that promotes learning and recruits widespread cortical networks, yet how distinct cingulate subregions contribute to its adaptive utility remains poorly understood. Here we used longitudinal one-photon calcium imaging in mice to compare dynamics in the anterior cingulate cortex (ACC) and retrosplenial cortex (RSC) across repeated unsignaled foot-shocks and fear conditioning and extinction paradigm. Both regions contained relatively stable ensembles that responded robustly to shocks, indicating shared encoding of acute nociceptive events. However, only the RSC flexibly re-organized its population activity when shocks were preceded by predictive cues. These anticipatory dynamics in the RSC predicted the rate of fear learning across individuals and subsequent extinction. By contrast, the ACC maintained shock-responsive ensembles with limited cue modulation. Instead, its dynamics encoded decisions to freeze, aligning with its role in encoding ongoing nociception and driving immediate defensive behavior. Together, these results reveal a division of labor in which the ACC emphasizes ongoing nociceptive processing, while the RSC transforms sensory signals into predictive codes that shape learning and memory. This specialization highlights how distributed cortical computations cooperate to generate the adaptive value of aversion. More broadly, our findings suggest that these regions assume complementary roles to address immediate sensory-motivational responses while flexibly reconfiguring to support long-term behavioral adaptation. Significance statement Pain engages widespread cortical circuits, yet how distinct cingulate subregions collaborate to shape its experience and utility remains unknown. Using longitudinal calcium imaging in mice, we demonstrate that both the anterior cingulate and retrosplenial cortex contain stable shock-responsive ensembles, but only the retrosplenial cortex flexibly remodels its activity when shocks are predicted by cues. These anticipatory dynamics not only predict fear learning but influence extinction. Our findings uncover a division of labor in which the anterior cingulate encodes ongoing nociception and immediate defensive actions, while the retrosplenial cortex transforms these signals into temporally structured representations that support learning and memory. This work highlights how specialized cortical computations interact to generate the adaptive value of pain.

  PublisherOA PDFDOI

• Modeling Withdrawal States in Opioid-Dependent Mice with Machine Learning

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-31

  preprintOpen accessSenior author

  Understanding opioid withdrawal behaviors in preclinical models is critical to improving therapeutic approaches for opioid use disorder (OUD). However, quantifying these withdrawal behaviors remains a difficult process for researchers, given the subtlety of behaviors and variation across individuals. To overcome these difficulties, we developed a scalable behavioral analysis pipeline using LUPE (Light aUtomated Pain Evaluator), an open-source framework integrating video acquisition, pose estimation, supervised and unsupervised classification, and expert-guided behavior discovery. Mice undergoing naloxone-precipitated opioid withdrawal were recorded and analyzed using DeepLabCut for markerless pose estimation. We hand-annotated withdrawal-specific behaviors, including jumping, genital licking, grooming, and paw tremors, and normal behaviors, including walking, rearing, and being still, using Behavioral Observation Research Interactive Software (BORIS) to generate frame-by-frame ethograms. The annotations and pose data were then imported into Active learning Segmentation of Open field in DeepLabCut (A-SOiD), an active learning platform for behavior classification. A-SOiD successfully detected some behaviors (e.g., grooming and rearing) which were of a longer duration, though other rapid behaviors (e.g., jumping and paw tremors) were inconsistently captured. While no novel behavioral motifs have been discovered yet, ongoing work aims to refine model performance. This LUPE-based pipeline sets the groundwork for standardized, high-resolution behavior quantification and is being applied to additional datasets to investigate whether new components of the withdrawal phenotype emerge across experimental conditions.

  PublisherOA PDFDOI

• Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles

  Nature Neuroscience · 2025-05-26 · 7 citations

  articleSenior author
  PublisherDOI

• Anatomical and molecular organization of the nociceptive medial thalamus

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-09

  articleOpen accessSenior authorCorresponding

  Abstract The medial thalamus (MTh) is a critical hub for integrating the affective and motivational dimensions of pain, yet its cellular and circuit organization remains poorly defined. Here, we combine activity-dependent genetic tagging, whole-brain clearing and light-sheet imaging, single-cell transcriptomics, and viral circuit tracing to build a comprehensive anatomical and molecular atlas of nociceptive and opioidergic neurons within the MTh. We show that acute and chronic pain activate distinct, spatially localized microdomains across multiple MTh subnuclei, including the central medial, interanteromedial, mediodorsal, and xiphoid nuclei. Activity-dependent tagging reveals a stable ensemble of nociceptive neurons that remains engaged across acute and chronic pain states, suggesting persistent thalamic encoding of affective nociception. Using fluorescent in situ hybridization, we find that most nociceptive-activated neurons express Oprm1 , and that nearly all Oprm1 + neurons are activated by nociceptive stimuli, identifying a pain-active, µ-opioid receptor-expressing population in MTh (MTh MOR ). Rabies-based tracing demonstrates that MTh MOR neurons receive convergent inputs from nociceptive and inhibitory regions including the anterior cingulate cortex, periaqueductal gray, parabrachial nucleus, and habenula, while projecting broadly to cortical, subcortical, and brainstem structures involved in pain, arousal, and motivation. Enkephalinergic inputs to MTh arise from distinct, non-nociceptive populations, suggesting parallel pathways for nociceptive transmission and endogenous opioid modulation. Together, these findings define the anatomical and molecular organization of the nociceptive medial thalamus and highlight MTh MOR neurons as a cell-type-specific substrate for the development of targeted opioid-based pain therapies. Abstract Figure

  PublisherDOI

• VTA µ-Opioidergic Neurons Facilitate Low Sociability in Protracted Opioid Abstinence

  Journal of Neuroscience · 2025-02-03 · 1 citations

  articleOpen accessSenior author

  Opioids initiate dynamic maladaptation in brain reward and affect circuits that occur throughout chronic exposure and withdrawal that persist beyond cessation. Protracted abstinence is characterized by negative affective behaviors such as heightened anxiety, irritability, dysphoria, and anhedonia, which pose a significant risk factor for relapse. While the ventral tegmental area (VTA) and μ-opioid receptors (MORs) are critical for opioid reinforcement, the specific contributions of VTA MOR neurons in mediating protracted abstinence-induced negative affect is not fully understood. In our study, we elucidate the role of VTA MOR neurons in mediating negative affect and altered brain-wide neuronal activities following forced opioid exposure and abstinence in male and female mice. Utilizing a chronic oral morphine administration model, we observe increased social deficit, anxiety-related, and despair-like behaviors during protracted forced abstinence. VTA MOR neurons show heightened neuronal FOS activation at the onset of withdrawal and connect to an array of brain regions that mediate reward and affective processes. Viral re-expression of MORs selectively within the VTA of MOR knock-out mice demonstrates that the disrupted social interaction observed during protracted abstinence is facilitated by this neural population, without affecting other protracted abstinence behaviors. Lastly, VTA MORs contribute to heightened neuronal FOS activation in the anterior cingulate cortex (ACC) in response to an acute morphine challenge, suggesting their unique role in modulating ACC-specific neuronal activity. These findings identify VTA MOR neurons as critical modulators of low sociability during protracted abstinence and highlight their potential as a mechanistic target to alleviate negative affective behaviors associated with opioid abstinence.

  PublisherOA PDFDOI

• A nociceptive amygdala-striatal pathway modulating affective-motivational pain

  Science Advances · 2025-07-23 · 6 citations

  articleOpen accessSenior authorCorresponding

  The basolateral amygdala (BLA) assigns valence to sensory stimuli, with a dedicated nociceptive ensemble encoding the negative valence of pain. However, the effects of chronic pain on the transcriptomic signatures and projection architecture of this BLA nociceptive ensemble are not well understood. Here, we show that optogenetic inhibition of the nociceptive BLA ensemble reduces affective-motivational behaviors in chronic neuropathic pain. Single-nucleus RNA sequencing revealed peripheral injury-induced changes in genetic pathways involved in axonal and presynaptic organization in nociceptive BLA neurons. Next, we identified a previously uncharacterized nociceptive hotspot in the nucleus accumbens shell that is innervated by BLA nociceptive neurons. Axonal calcium imaging of BLA projections to the accumbens and chemogenetic inhibition of this pathway revealed pain-related transmission from the amygdala to the medial nucleus accumbens, facilitating both acute and chronic pain affective-motivational behaviors. Together, this work defines a critical nociceptive amygdala-striatal circuit underlying pain unpleasantness across pain states.

  PublisherDOI

Recent grants

• Synaptic mechanisms of opioid-induced hyperalgesia and tolerance

  NIH · $58k · 2016–2017

• Deconstructing the network mechanisms of chronic pain and reward in the amygdala

  NIH · $350k · 2017–2019

• Deconstructing the network mechanisms of chronic pain and reward in the amygdala

  NIH · $744k · 2019–2023

• Harnessing cortical neuromodulation to disrupt pain perception

  NIH · $2.6M · 2020–2025

• NIH Grant F31DA032496

  NIH · $47k · 2015

Frequent coauthors

• Grégory Scherrer

  University of North Carolina at Chapel Hill

  36 shared

• Bradley K. Taylor

  11 shared

• Dong Wang

  University of Nebraska Medical Center

  10 shared

• Sarah Low

  Massachusetts General Hospital

  10 shared

• J. Cobb Scott

  10 shared

• Vivianne L. Tawfik

  10 shared

• Amaury François

  Inserm

  9 shared

• Theodore D. Satterthwaite

  Children's Hospital of Philadelphia

  8 shared

Labs

• The Corder Lab at PennPI