Our laboratories use imaging and electrophysiological recording techniques to investigate basic brain signaling mechanisms that are involved in migraine, stroke, brain tumors, and other disorders of the central nervous system.
GLIAL CELL SIGNALING
Glial cells had previously been considered to play primarily a passive role in brain activity. However, recent studies have shown that glial cells are capable of extensive intercellular communication and active modulation of neuronal and vascular function. We have hypothesized that glial cells could play a primary role in the propagated waves of brain activity that are seen in patients with migraine and stroke. We use microscopic imaging techniques to visual changes in cellular calcium concentration in glial cells that may mediate this propagated activity.
NEURONAL SIGNALING AND PHARMACOLOGY
Migraine involves changes in the excitability of neurons in multiple brain regions that may trigger attacks, and also activation of neurons that transmit pain signals that generate headache. We study the function of neurons from the brain cortex that are thought to generate migraine aura, as well as neurons from the trigeminal ganglion that are believed to transmit the pain of headache as well as other facial pain disorders. We study the effects of different neurotransmitters on neuronal signaling -- we are particularly interested in the role of opioids in the regulation of brain excitability and pain transmission. We also study the effects of the neurotransmitters glutamate, GABA, serotonin, ATP, and adenosine among others with the goal of identifying novel therapies that target the cellular signaling pathways that are activated by these transmitters.
CORTICAL SPREADING DEPRESSION (CSD)
CSD is a slowly propagated wave of brain activity that is believed to be a primary mechanism underlying the migraine aura, and may also occur in patients with migraine without aura. Growing evidence indicates that CSD in rodents represents a valid model for human migraine mechanisms, and a platform for the identification of new therapies. We use optical imaging and electrophysiological recording techniques to characterize the effects of genes, hormones, and pharmacological agents on the properties of cortical spreading depression. The goal of these studies is to better understand the fundamental causes of migraine, and to identify novel treatments for migraine based on their ability to modulate CSD.
IMAGING ACUTE BRAIN INJURY AND FUNCTIONAL RECOVERY FROM BRAIN INJURY
Acute stroke and other types of brain injury trigger repetitive CSD events that are similar to those that are believed to occur in migraine. The functional consequences of these events are not well understood, but early evidence indicates that modulation of the CSD events associated with brain injury may represent a novel approach to improving long-term recovery. We use imaging techniques to visualize both the events that occur during acute stroke, as well as the process of recovery of brain function that occurs in the weeks following stroke.
MOUSE BEHAVIORAL ASSAYS RELEVANT TO MIGRAINE
In collaboration with Amynah Pradhan in the Department of Psychiatry, we have developed assays of mouse behavior that may be relevant to migraine. Mice respond to the migraine trigger nitroglycerin with hypersensitivity to mechanical and thermal stimuli that is progressive and sustained with repetitive administration over time. In addition to this hyperalgesia, mice respond to nitroglycerin with aversive behavior such that they avoid the location where they received the nitroglycerin. This assay, known as conditioned place aversion, is an indication of the negative emotional state produced by a given stimulus. Our initial studies indicate that these assays may have predictive value for acute migraine therapies.