Thursday 7 November 2002
SFN 2002 - Day 5
by Damaris Christensen
Investigators: Danielle Piomelli, Roger Nicoll and Wade Regehr
Typically, a nerve impulse is sent from a presynaptic neuron across a short gap to a post-synaptic neuron, which accepts the chemical signal and passes it along. Last year, scientists suggested that naturally produced cannabinoids can do something unusual: send messages from post-synaptic cells to their presynaptic partners.
This form of communication may be particularly important in tuning the activity of neural networks in the hippocampus and cerebellum, areas of the brain involved in memory, learning, and coordination of movement.
Now, scientists are digging deeper to understand the retrograde mechanisms through which cannabinoids produce their unusual effects. The compounds can work to excite or inhibit neurons from firing, and this may prove to be an important way the brain controls its response to new stimuli, or demonstrates plasticity, said Roger Nicoll of the University of California, San Francisco.
Nicoll and his colleagues have shown that mice lacking receptors for cannabinoids do not have this characteristic nerve-cell response. They've also identified another protein that seems to interfere with cannabinoid signaling through a different receptor. Teasing out the molecules in this process is important for further study of the mechanisms, he said.
Wade Regehr of Harvard Medical School has shown that blocking calcium signaling interferes with the retrograde signaling process. Calcium can be found around neurons in much higher concentrations than expected, he reported. In some cases, this seems to trigger the post-synaptic neuron to make the cannabinoid anandamine, which seeps across the gap between nerve cells and slows firing of the presynaptic neuron. "There were just unexpectedly high concentrations of calcium in the dendrite," he said, a finding that may help scientists tease out why retrograde signaling is used. "It completely changes the way I think about the endocannabinoid system," he said.
Regehr also reported that activation of just a few nerve fibers for short bursts of activity could trigger retrograde signaling, and that the signals can be synapse-specific. "The post-synaptic cell is receiving a bunch of signals and obviously performing some kind of computation to regulate its output and input," he said. "But as yet we really don't know what it is doing."
"It's possible that retrograde signaling is used to regulate the strength of the synapse," said Daniele Piomelli of the University of California, Irvine.
Some studies have indicated that depressed patients have decreased amounts
of endocannabionids in the brain, Piomelli said, hinting that further insights
into the process could lead to new drug targets.
© Elsevier Science Limited 2002