research

The mission of the Corder Lab @ Penn is to decipher the neural basis of how the brain generates the perception of pain and aversive memories, and how pathological dysfunction within these brain networks promotes the transition to chronic pain and drug abuse. Utilizing the pharmacology of opioids and psychedelics, in combination with in vivo imaging of neural activity, neuroanatomical tracing, and optical neuromanipulation techniques, our group continues to deconstruct the brain circuits and molecular mechanisms involved in pain and pleasure.

Additionally, our lab builds machine vision and deep learning algorithms to decode complex animal behaviors, providing deeper insights into how neural circuits drive pain behaviors. Our autoamted, preclinical behavior systems enhance the accuracy and efficiency of identifying effective analgesics, ultimately leading to better pain management therapies for humans.

From our investigations, we aim to identify translational targets for the development of novel therapeutics and gene therapies to reduce mental health disorders associated with chronic pain and lessen the reliance on prescription opioids.

NEURAL CODING OF AFFECTIVE STATES

Combining machine learning with "miniscope" calcium imaging from large populations of neurons deep in the brain of behaving animals, allows us to decode the neural activities underlying the emotional component of painful and hedonic experiences. 

Pain is an unpleasant experience that commands attention and the engagement of motivational protective behaviors to limit exposure to noxious stimuli. In contrast, chronic pain is not merely a persistent sensory disorder, but a neurological disease of affective dysfunction that serves no survival function. As such, chronic pain negatively impacts the mental state, professional goals, and personal relationships of over 100 million Americans. However, it is unclear how the nociceptive systems in the brain undergo pathological maladaptations to enable the transition to a chronic pain state.

Figure adapted from Corder et al. An amygdalar neural ensemble that encodes the unpleasantness of pain Science. 2019

CONTROL OF MOTIVATED BEHAVIORS DERIVED FROM FUNCTIONALLY DISTINCT NEURAL CIRCUITS

Brining together mouse genetics, viral tracing, pharmaco- and optogenetics permits the functional interrogation of neural circuits and spinal cord::brain pathways that shape complex behaviors. 

In particular, painful experiences are constructed from neural information relating not only sensory, but also emotional, interoceptive, inferential, and cognitive data, which coalesce into a unified conscious perception of pain. If we can understand the processes by which these different functional dimensions of pain perceptions are generated from distinct brain networks, in particular those encoding the negative affective or unpleasantness of pain, then we can generate new dynamic frameworks for modeling the emergence of unrelenting chronic pain.

Figure adapted from Corder et al. An amygdalar neural ensemble that encodes the unpleasantness of pain Science. 2019

GENETIC, MOLECULAR, AND SYNAPTIC REMODELING BY OPIOIDS AND DRUGS OF ABUSE

With the staggering prevalence of chronic pain, the broad use of opioids for pain management has increased markedly in the past decades. This increase in opioid prescriptions has been accompanied by a sharp rise in the incidence of addiction and opioid-related mortality, a phenomenon termed the Opioid Epidemic. Our lab will traverse two research paths to battle the Opioid Epidemic: discovering non-opioid analgesic therapies that could replace opioids or improving current opioid analgesics. For both paths, a decisve first step must be the complete resolution of the analgesic mechanisms of opioids, at the synaptic, circuit, and network levels. 

Data from Corder et al. Loss of μ opioid receptor signaling in nociceptors, but not microglia, abrogates morphine tolerance without disrupting analgesia. Nature Medicine. 2017