Duke University. US: Neuroscientists find hevin in the newborn brain. Shortly
after birth, human brains expand rapidly with the experience of an
entirely new world. During this period, neurons in the newborn brain
compete with one another to form lasting connections, called synapses. A
new study by Duke researchers provides a close-up of synapse refinement
and identifies a protein that is crucial in this process. Disruptions
in the protein, called hevin, have previously been linked to autism,
depression and suicide, but the molecule’s role in the developing brain
was mostly unknown until now.
The researchers focused on tiny
protrusions of the neuron called spines that harbor synaptic
connections. Neuroscience has long assumed that these little nubs serve
as sites for single synapses.
But this study, which appeared early online last month in the open access journal eLife,
shows that in the brains of newborn mice, some of the spines initially
receive two or more inputs. As the brain matures, the spines then
receive one. A technique known as three-dimensional electron microscopy
made this observation possible.
“I was very excited about this
finding,” said first author William Christopher Risher, a postdoctoral
researcher in the laboratory of senior author Çagla Eroglu. “I went to
check the literature to see if anyone’s really described
[multiple-synapse spines] before. And there really hasn’t been much.”
The
group also found that mice that are missing the gene that codes for the
protein hevin retain more of these multiple synapses compared with
normal mice. As the developing brain prunes away synapses to become more
efficient, this could present problems.
Hevin was first
identified in the miniscule spaces between synapses in 1990. However,
gene expression studies showed that it is actually churned out by
non-neuronal cells called astrocytes.
Interested in the
relationship between astrocytes, synapse formation and disease, Eroglu’s
group showed in 2011 that hevin triggers the formation of new neural
connections. “That was the first description of hevin’s function in the
nervous system,” said Eroglu, an assistant professor of cell biology and
neurobiology, and a member of the Duke Institute for Brain Sciences.
“We
continued studying this protein because it is abundant in many brain
regions, [both] when synapses are forming and also during adulthood,”
Eroglu said.
In the cortex, an area of the brain important for
complex thought and awareness, hevin encourages inputs from the thalamus
-- a part of the brain that acts as a relay center for sensory and
motor information -- while it discourages inputs from local neurons
within the cortex, the group found.
The spines that receive
multiple synapses tend to be occupied by both cortical and thalamic
connections at the same time, suggesting that these spines are sites for
synaptic competition.
The balance of those two types of types
of connections in the cortex could go awry in neurological diseases such
as autism and depression, Eroglu said. The group is now studying the
molecular mechanisms of hevin and its potential contribution to health
and disease.