M.R. Bauer Distinguished
Roger Nicoll, M.D.
Department of Cellular and Molecular Pharmacology
University of California, San Francisco
San Francisco, California
February 19-23, 2001
Presynaptic Neurotransmitter Receptors and the Control of Transmitter Release
For the week of February 19-23, Dr. Roger Nicoll from UCSF was a visiting professor at Brandeis. On Monday, February 19, Nicoll presented his research in a Bauer Lecture. His topic, "Presynaptic Neurotransmitter Receptors and the Control of Transmitter Release," focused on two different types of plasma membrane receptors, which act to modulate synaptic transmission between hippocampal neurons.
The first half of the talk described a long-lasting, facilitatory role for kainate receptors on Granule cell synapses (also called Mossy fiber synapses) in area CA3 of the hippocampus. These receptors act presynaptically as autoreceptors at these synapses to facilitate further release of the excitatory neurotransmitter glutamate. This mechanism is relatively novel because kainate receptors are ionotropic receptors, which can mediate fast effects on ionic conductance. Prior research on presynaptic receptors in the brain have shown their effects to be mediated mainly through metabotropic receptors, which activate G-proteins and other molecular mechanisms in the cell, resulting in a slower and more long-lasting cellular response. The activation of presynaptic kainate receptors appears to be part of a positive feedback loop. High levels of glutamate released by the granule cell activate kainate receptors on its own Dresynaptic terminal. The activated kainate receptors further increase the release of glutamate.
For the second half of the lecture, Nicoll focused on describing the physiological function of cannabinoid receptors in the brain. Cannabinoid receptors were originally discovered to be the receptor that Cannabis sativa, or marijuana, binds to in the brain. It can be found on a subset of inhibitory interneurons (which release GABA) in the hippocampus called basket cells, located in the pyramidal cell layer.
Since their discovery, endogenous ligands for this receptor have been discovered and their effect on cellular function has been examined. The activation of these receptors on these GABAergic neurons results in a calcium-dependent, depolarization- induced suppression of inhibition (DSI), which decreases the frequency of spontaneous miniature IPSPS, thus decreasing the probability of GABA release from these interneurons. These basket cells make synaptic contacts onto neighboring pyramidal cells in the hippocampus and are involved in the entrainment of pyramidal cells and in the modulation of theta-wave activity in the hippocampus. Nicoll's findings can potentially shed some light on the role that Cannabinoids play in changes in cognitive function.