signal transmission between neurons is vital for normal neurologic and
cognitive function. In the brain, cell-to-cell communication occurs at
the junction that connects two neurons - a structure known as a synapse.
any given moment, neurotransmitter-carrying vesicles are on standby at
designated docking stations, called active zones, each awaiting a
trigger to release its load across the synaptic cleft and deliver it to
the next neuron.
‘Not all launch-ready neurotransmitter vesicles need to be docked in the active zone when a trigger arrives. Neurons form a remote critical reserve of vesicles that can be quickly marshaled in times of high demand.’
Signal strength and speed are determined by the
number of vesicles ready and capable of releasing their cargo to the
Neuroscientists have thus far surmised that
destroying the docking stations that house neurotransmitter-loaded
bubbles would cause all cell-to-cell communication to cease. A new study by the Harvard Medical School suggest otherwise.
The mice study reveals that dismantling the
docking stations that house these signal-carrying vessels does not fully
disrupt signal transmission between cells. The team's experiments, described in the journal Neuron
, suggest the presence of mechanisms that help maintain partial communication despite serious structural aberrations.
results not only address one of the most fundamental questions about
neuronal activity and the way cells in the brain communicate with each
other but uncover a few surprises too," said Pascal Kaeser, senior author on the study and assistant professor of neurobiology at HMS.
"Our findings point to a fascinating underlying resilience in the nervous system."
examine the relationship between docking stations and signal
transmission, researchers analyzed brain cells from mice genetically
altered to lack two key building proteins, the absence of which led to
the dismantling of the entire docking station.
measured signal strength in neurons with missing docking stations, they
observed that those cells emitted much weaker signals when demand to
transmit information was low. However, when stronger triggers were
present, these cells transmitted remarkably robust signals, the
"We would have guessed that signal
transmission would cease altogether but it didn't," said Shan Shan Wang,
a neuroscience graduate student in Kaeser's lab and a co-first author
of the study. "Neurons appear to retain some residual communication even
with a key piece of their communication apparatus missing."
of one active zone building block, a protein called RIM, led to a
three-quarter reduction in the pool of vesicles ready for release.
Disruption of another key structural protein, ELKS, resulted in
one-third fewer ready-to-deploy vesicles. When both proteins were
missing, however, the total reduction in the number of releasable
vesicles was far less than expected. More than 40% of a neuron's
vesicles remained in a "ready to launch" state even with the entire
docking station broken down and vesicles failing to dock.
finding suggests that not all launch-ready vesicles need to be docked in
the active zone when a trigger arrives. Neurons, the researchers say,
appear to form a remote critical reserve of vesicles that can be quickly
marshaled in times of high demand.
"In the absence of a docking
sites, we observed that vesicles could be quickly recruited from afar
when the need arises," said Richard Held, an HMS graduate student in
neuroscience and co-first author on the paper.
The team cautions
that any clinical implications remain far off, but say that their
observations may help explain how defects in genes responsible for
making neuronal docking stations may be implicated in a range of