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.
