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@ U S T . H K
The infinitely complex human brain
has recently given up more of its
secrets. The Zhang Lab, a global leader
in neuronal structural biology, has
discovered the answer to a question that
has been puzzling neuroscience for 60
years. Led by Prof Mingjie Zhang, the
team has also shown that this finding
has significant potential for greater
understanding of neuropsychiatric
disorders such as autism and
schizophrenia, which afflict millions
around the world.
The question involves one of the
Zhang Lab’s areas of focus over the
past two decades: transmission of
neuronal signals in synapses. In the
human brain, the 1.5-liter powerhouse
that determines everything about us,
information is transmitted through
around 10
neurons. They send or
receive signals from other cells, and
from one neuron to the next, through
synapses, which number around 10
Given the large numbers and nanometer
scale of the molecular machinery,
tracing the atomic-level underpinnings
of this network is a daunting challenge.
But specializing in synapses, a
fundamental unit for all kinds of
neurons, has provided the Zhang Lab
with a valuable way of cutting through
such complexity. Synapses function
as signal receiving, processing and
transmitting apparatuses as well as
memory storage and retrieval sites.
Derived from the Greek word meaning
conjunction, they encompass a
jumping-off point for the signal, called
the presynaptic terminal, a fluid-filled
space or cleft, and the landing area or
postsynaptic density.
Transmission of neuronal signals in synapse
Prof Mingjie Zhang (right)
with Dr Menglong Zeng.
While the postsynaptic density
and its role as the signal receiving and
processing unit was first observed
six decades ago, how it forms and
organizes itself remained a mystery. It
is this enigma that the Zhang Lab has
successfully solved.
A focus on two abundant proteins in
the postsynaptic density, SynGAP and
PSD-95, led to thediscovery. Theseproteins
were already of interest to scientists as
they were known to play a major role in
learning and memory; and if mutated,
were implicated in disorders such as
autism and epilepsy. However, the break-
through was accomplished by building
on the Zhang Lab’s years of leading
studies on synaptic signaling complex
assembly and regulation; and its systematic
work to comprehend how the proteins
critical for receiving and interpreting
diverse brain signals are coordinated to
form synaptic functional networks.
I chose to focus on
the synapse, a tiny
compartment just 0.5
micron or less in diameter,
because it is a basic unit
of communication for
all kinds of neurons.
The principles we learn
from our studies will be
applicable to essentially
every aspect of
brain cells
Kerry Holdings Professor of Science,
Academician, Chinese Academy of Sciences
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