Neil Harrison, PhD
Professor of Anesthesiology & Pharmacology
Dr. Harrison’s main area of research interest is in synaptic transmission, especially at inhibitory synapses, which are necessary for the normal processing of information in the mammalian brain. Failure of synaptic inhibition leads to epilepsy, while enhancement of synaptic inhibition is associated with reduced anxiety, muscle relaxation, sedation, hypnosis and anesthesia. The lab studies the details of inhibitory synaptic function, its modulation and plasticity, using a variety of modern electrophysiological and molecular biological techniques. Projects within the lab study these synapses at several different levels of organization, including brain slice, single cell and subcellular preparations. A major focus of the lab is on the GABA-A receptor, the principal receptor protein at inhibitory synapses in the brain. The lab personnel include physiologists, biophysicists, molecular biologists and pharmacologists.
Jose Moron-Concepcion, PhD
Associate Professor of Anesthesiology
While abuse and addiction to opiates has been a long-standing problem, the recent surge in abuse of opiate analgesics foreshadows the potential for rising rates of addiction to opiates. Repeated administration of drugs of abuse, such as morphine, causes a progressive and persistent sensitization of its locomotor stimulant and positive reinforcing effects. Sensitization to morphine can be sustained for several months after drug cessation and serves as a useful animal model of plasticity and the neuroadaptations associated with repeated administration of opioids having abuse potential. Studies show that sensitization has a close relationship with relapse, compulsive drug-seeking, and drug-taking behavior. Recent evidence suggests a role for the hippocampus in controlling these long-lasting behavioral adaptations. Investigation of an opiate-induced sensitization may help us to better understand the relapse mechanisms and provide new strategies for the treatment of drug addiction. Additionally, the key role of hippocampal synapses in learning and memory suggests that an understanding of the role of its specialized subcellular compartments in addictive processes is essential. Glutamatergic systems are thought to be involved in opiate-induced neuronal and behavioral plasticity although the mechanisms underlying these effects are only beginning to be understood. In our lab we analyze the role of synaptic AMPA glutamate receptors in the neuronal adaptations associated with repeated administration of morphine. More specifically, we study how morphine administration modulates synaptic transmission and plasticity at hippocampal synapses by altering the expression and composition of AMPA glutamate receptors, and how these adaptive effects will persist over time leading to neuroadaptions in glutamatergic synaptic function which could be responsible for the long-term behavioral sensitization induced by repeated morphine administration.
A second project in the lab is focused in elucidating the molecular mechanisms underlying morphine-induced pain sensitivity. It’s known that abrupt abstinence or withdrawal from opiate drugs causes a series of severe adverse symptoms, which keep drug-dependent individuals craving continued opiates. One of the core of withdrawal symptoms is an increase in pain sensitivity (pain sensitization or hyperalgesia). This pain sensitization is due to synaptic plasticity, particularly in the spinal cord and primary afferents. It has been demonstrated that AMPA glutamate receptor trafficking within the spinal cord is involved in the development of pain sensitivity. In our lab we analyze changes in AMPA receptor expression occurring in sensitivity at two different levels: 1) spinal cord and 2) primary afferent neurons. These studies are performed by combining behavioral paradigms with biochemical and state-of-art electrophysiological techniques.
Joachim Scholz, MD
Assistant Professor of Anesthesiology and Pharmacology, Columbia University College of Physicians and Surgeons
Area of Research - Peripheral neuropathy, pain
Special Focus -Cellular and molecular mechanisms of chronic pain
Pain serves an important protective function: it is a physiological response to harmful environmental or internal stimuli that alerts us of imminent tissue damage. However, in the presence of inflammation or repeated injury, pain no longer accurately reflects the nature or intensity of these stimuli. The sensation of pain increases and spreads beyond the injury site. Pain may even occur spontaneously, in the absence of a recognizable stimulus. Chronic back pain and pain associated with osteoarthritis are clinical examples of such inflammatory pain.
Neuropathic pain develops after a lesion or disease that directly affects the nervous system. Neuropathic pain has long been considered an exclusively neuronal “affair”. However, it is now clear that nerve lesions, too, provoke a marked inflammatory response that involves circulating and resident immune cells in the periphery and glial cell populations in the central nervous system. My laboratory is interested in identifying the molecular messages that neurons, immune cells and glia exchange with each other. We want to determine the signals that trigger recruitment and activation of immune and glial cells, and examine how signals released from immune and glial cells alter neuronal activity.
A key relay station for somatosensory information including pain is the dorsal horn of the spinal cord. Here, local interneurons and descending pathways from the brain jointly control the processing of afferent input. Nerve injury disrupts these control mechanisms profoundly. Using persistent neuropathic pain as a model of maladaptation in the nervous system, we study the impact of peripheral nerve lesions on the balance between excitatory and inhibitory regulation of synaptic transmission in the dorsal horn and the consequences for neuronal survival and function.
In an exciting new avenue of research, we are using stem cell technology to examine intrinsic risk factors for neurodegeneration and pain in diabetic neuropathy. The central idea behind this approach is to develop a model of neuropathy based on human induced pluripotent stem cells (iPSCs) that we derive from patients with type 2 diabetes. The phenotype of these patients has been carefully characterized to capture neuropathic deficits and differentiate between mechanistically distinct features of neuropathic pain. To generate neurons from iPSCs, we collaborate with colleagues in the Stem Cell Initiative at Columbia University and the Harvard Stem Cell Institute. Planned and ongoing research includes the differentiation and functional analysis of these neurons, the exploration of mechanisms responsible for peripheral neurodegeneration and pain, and the identification of potential targets for therapeutic intervention.
Robert A. Whittington, MD
Associate Professor of Anesthesiology
My current research interest primarily focuses on the impact of anesthesia and surgery on the neuropathogenesis of Alzheimer’s disease (AD). Using transgenic mouse and cellular models of AD, my laboratory is investigating the impact of prolonged anesthesia exposure on the development of tau protein-related neurofibrillary pathology, one of the neuropathological hallmarks of Alzheimer’s. The long-term goal of this research is to better understand how anesthesia and surgery modulate AD-related neuropathogenic pathways in order to identify perioperative treatment strategies that preserve cognitive function in those patients who are at risk for postoperative cognitive decline as well as incident dementia.