Gregory W. Terman, Ph.D./M.D.
Dept.: Professor, Department of Anesthesiology
Neuroscience Focus Groups: Behavioral Neuroscience, Excitable Membranes and Synaptic Transmission, Neurotransmitters, Modulators, Transporters and Receptors, Sensory Systems
The central nervous system has been found capable of remarkable plasticity, demonstrating functional and structural changes as a result of incoming stimuli, which then alter the response of that neural system to future stimuli. Such neuroplasticity may play a role in such diverse phenomena as neural protection and regeneration following stroke, epileptogenesis, opiate tolerance, learning and memory and certain chronic pain states. In the last several years we have studied the role of opiates and their receptors in modulating long-term potentiation (LTP) in vitro in the hippocampal and spinal cord slice preparations.
In the hippocampus, rapid repeated stimulation of afferents to primary cells in the dentate and CA3 regions produces long lasting increases in synaptic strength which can be blocked by application of kappa opiate receptor agonists. Moreover, we find that endogenous kappa opiates (the dynorphins) may modulate such long-term increases in hippocampal excitability between adaptive levels which allow learning and memory to take place and pathological levels which can result in epilepsy. Modulation of synaptic plasticity appears to rely on afferent activated calcium channel dependent dendritic dynorphin release and retrograde activation of pre-synaptic kappa opiate receptors to inhibit the release of glutamate and thus LTP induction.
More recently we have begun studying opiate modulation of activity dependent LTP in pain pathways of the spinal cord as a model for the pathogenesis of certain chronic pain states. Repeated stimulation of the tract of Lissauer produces long-term potentiation of evoked potentials in the dorsal horn of the spinal cord. This LTP depends in part on NMDA receptors and it’s induction can be inhibited by mu opioids. We are currently utilizing infrared aided Nomarski optics and whole cell voltage clamp techniques to record specifically from fluorescently labelled spinothalamic tract cells and to study the pre- and post-synaptic mechanisms which underlie opioid modulation of spinal cord synaptic plasticity and their implications for the causes and treatments of chronc pain.