About

Matthew Banghart, Ph.D., is the Principal Investigator of the Banghart Lab at UCSD, which launched in the Fall of 2016. Originally trained as an organic chemist, Dr. Banghart transitioned into neuroscience during his PhD training at UC Berkeley under the mentorship of Dirk Trauner and Rich Kramer. There, he developed methods for regulating ion channels with light, marking the beginning of his transformation into a neuroscientific research. He then pursued postdoctoral studies as a Helen Hay Whitney fellow with Bernardo Sabatini at Harvard Medical School, focusing on the neurophysiology of striatal neuropeptides. This postdoctoral work solidified his interest in understanding how neuromodulators influence behavior. Outside of his research, Dr. Banghart enjoys outdoor activities such as running, cycling, camping, hiking, snowboarding, and spending time with his family in La Jolla.

Research topics

• Neuroscience
• Pharmacology
• Biology
• Chemistry
• Cell biology
• Biochemistry
• Biophysics
• Medicine
• Internal medicine

Selected publications

• Mimicking opioid analgesia in cortical pain circuits

  Nature · 2026-01-07 · 2 citations

  articleOpen access

  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

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

  Neuron · 2026-04-01

  articleOpen accessSenior author

  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

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

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-16

  preprintOpen accessSenior authorCorresponding

  In placebo analgesia, prior experience and expectations lead to pain suppression by the administration of an inert substance, but causal evidence for its neural basis is lacking. To identify the underlying neural circuits, we reverse-translated a conditioned placebo protocol from humans to mice. Surprisingly, the placebo effect suppresses both nociception and unconditioned emotional-motivational pain-related behavior. Descending pain modulatory neurons in the periaqueductal gray (PAG) are critical for both morphine and placebo antinociception. The placebo effect depends on input to the PAG from the medial prefrontal and anterior cingulate cortices, but not anterior insular cortex. Conditioning enhances noxious stimulus-evoked endogenous opioid release in the PAG to produce analgesia. Our results suggest that cortical control of the descending pain modulatory system (DPMS) is gated by rapid endogenous opioid signaling in the PAG during placebo trials. This study bridges clinical and preclinical research, establishing a central role for the DPMS in placebo analgesia.

  PublisherDOI

• A Chemically Stable Photocaged Noradrenaline

  ACS Chemical Neuroscience · 2025-07-08 · 1 citations

  articleOpen accessSenior authorCorresponding

  Photoactivatable neurotransmitters provide spatiotemporally precise experimenter control over endogenous receptor activation in living tissue. The resulting optical stimulus-neuronal response relationship provides a sensitive assay that can drive quantitative studies into receptor signaling. Here, we report a photocaged derivative of the prominent catecholamine neurotransmitter noradrenaline (NA). Appending a carboxynitroveratryl (CNV) caging group to the 4-hydroxyl of the catechol group produced CNV-NA, which displays good aqueous solubility and chemical stability. We verified CNV-NA’s lack of activity at α1B- and β2-adrenoreceptors expressed in HEK cells using a live-cell cAMP assay. We validated CNV-NA photoactivation at native α2-adrenoreceptors in brain slices of rat locus coeruleus using whole cell electrophysiological recordings. Monitoring the stereotyped outward current response to repeated CNV-NA photoactivation revealed that the neuropeptide substance P suppresses α2-adrenoreceptor signaling in locus coeruleus neurons. This work adds a new reagent to the growing library of photocaged neuroactive ligands, thereby expanding the scope and applications of photopharmacology.

  PublisherDOI

• Unlocking opioid neuropeptide dynamics with genetically encoded biosensors

  Nature Neuroscience · 2024-07-15 · 50 citations

  articleOpen access

  Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.

  PublisherDOI

• Mimicking opioid analgesia in cortical pain circuits

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-04-29 · 13 citations

  preprintOpen access

  The anterior cingulate cortex is a key brain region involved in the affective and motivational dimensions of pain, yet how opioid analgesics modulate this cortical circuit remains unclear. 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 behaviors and is selectively modulated by morphine. Using deep-learning behavioral 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 behaviors without altering sensory detection or reflexive responses, mirroring how opioids alleviate pain unpleasantness in humans. Leveraging these findings, we built a biologically inspired gene therapy that targets opioid-sensitive neurons in the cingulate using a synthetic mu-opioid receptor promoter to drive chemogenetic inhibition. This opioid-mimetic gene therapy recapitulated the analgesic effects of morphine during chronic neuropathic pain, thereby offering a new strategy for precision pain management targeting a key nociceptive cortical opioid circuit with safe, on-demand analgesia.

  PublisherOA PDFDOI

• Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation

  Science Advances · 2024-04-26 · 45 citations

  articleOpen accessSenior authorCorresponding

  The supraspinal descending pain modulatory system (DPMS) shapes pain perception via monoaminergic modulation of sensory information in the spinal cord. However, the role and synaptic mechanisms of descending noradrenergic signaling remain unclear. Here, we establish that noradrenergic neurons of the locus coeruleus (LC) are essential for supraspinal opioid antinociception. While much previous work has emphasized the role of descending serotonergic pathways, we find that opioid antinociception is primarily driven by excitatory output from the ventrolateral periaqueductal gray (vlPAG) to the LC. Furthermore, we identify a previously unknown opioid-sensitive inhibitory input from the rostroventromedial medulla (RVM), the suppression of which disinhibits LC neurons to drive spinal noradrenergic antinociception. We describe pain-related activity throughout this circuit and report the presence of prominent bifurcating outputs from the vlPAG to the LC and the RVM. Our findings substantially revise current models of the DPMS and establish a supraspinal antinociceptive pathway that may contribute to multiple forms of descending pain modulation.

  PublisherOA PDFDOI

• In vivo photopharmacology with light-activated opioid drugs

  Neuron · 2023-10-16 · 37 citations

  articleOpen accessSenior authorCorresponding

  Traditional methods for site-specific drug delivery in the brain are slow, invasive, and difficult to interface with recordings of neural activity. Here, we demonstrate the feasibility and experimental advantages of in vivo photopharmacology using "caged" opioid drugs that are activated in the brain with light after systemic administration in an inactive form. To enable bidirectional manipulations of endogenous opioid receptors in vivo, we developed photoactivatable oxymorphone (PhOX) and photoactivatable naloxone (PhNX), photoactivatable variants of the mu opioid receptor agonist oxymorphone and the antagonist naloxone. Photoactivation of PhOX in multiple brain areas produced local changes in receptor occupancy, brain metabolic activity, neuronal calcium activity, neurochemical signaling, and multiple pain- and reward-related behaviors. Combining PhOX photoactivation with optical recording of extracellular dopamine revealed adaptations in the opioid sensitivity of mesolimbic dopamine circuitry in response to chronic morphine administration. This work establishes a general experimental framework for using in vivo photopharmacology to study the neural basis of drug action.

  PublisherOA PDFDOI

• Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-10-10 · 6 citations

  preprintOpen accessSenior authorCorresponding

  The supraspinal descending pain modulatory system (DPMS) shapes pain perception via monoaminergic modulation of sensory information in the spinal cord. However, the role and synaptic mechanisms of descending noradrenergic signaling remain unclear. Here, we establish that noradrenergic neurons of the locus coeruleus (LC) are essential for supraspinal opioid antinociception. Unexpectedly, given prior emphasis on descending serotonergic pathways, we find that opioid antinociception is primarily driven by excitatory output from the ventrolateral periaqueductal gray (vlPAG) to the LC. Furthermore, we identify a previously unknown opioid-sensitive inhibitory input from the rostroventromedial medulla (RVM), the suppression of which disinhibits LC neurons to drive spinal noradrenergic antinociception. We also report the presence of prominent bifurcating outputs from the vlPAG to the LC and the RVM. Our findings significantly revise current models of the DPMS and establish a novel supraspinal antinociceptive pathway that may contribute to multiple forms of descending pain modulation.

  PublisherOA PDFDOI

• In vivo photopharmacology with a caged mu opioid receptor agonist drives rapid changes in behavior

  Nature Methods · 2023 · 35 citations

  Senior authorCorresponding
  • Chemistry
  • Neuroscience
  • Pharmacology
  PublisherOA PDFDOI

Recent grants

• Compartment-Specific Signaling Of Striatal Opioid Peptides in Reward-Guided Behav

  NIH · $243k · 2013–2016

• Compartment-specific signaling of striatal opioid peptides in reward-guided behavior

  NIH · $747k · 2017–2021

Frequent coauthors

• Bernardo L. Sabatini

  Howard Hughes Medical Institute

  43 shared

• Dirk Trauner

  27 shared

• Luke D. Lavis

  Janelia Research Campus

  25 shared

• Ruchir C. Shah

  Howard Hughes Medical Institute

  25 shared

• John T. Williams

  25 shared

• Richard Krämer

  University of California, Berkeley

  15 shared

• Xinyi Jenny He

  University of California, San Diego

  11 shared

• Alexandre Mourot

  Laboratoire Plasticité du Cerveau

  10 shared

Labs

• Banghart LabPI

  The Banghart Lab launched at UCSD in the Fall of 2016.

Education

• PhD, Chemistry

  University of California Berkeley

  2008

Awards & honors

• Helen Hay Whitney Postdoctoral Fellow
• K99/R00 Pathway to Independence Award from NIDA