Enzyme prevents brain activity from getting out of control
Mechanism identified alters the coupling of nerve cells

Date:
April 20, 2022
Source:
University of Bonn
Summary:
The brain has the ability to modify the contacts between
neurons. Among other things, that is how it prevents brain activity
from getting out of control. Researchers have now identified a
mechanism that plays an important role in this.



FULL STORY ==========================================================================
The brain has the ability to modify the contacts between neurons. Among
other things, that is how it prevents brain activity from getting out
of control.

Researchers from the University Hospital Bonn, together with a team from Australia, have identified a mechanism that plays an important role in
this. In cultured cells, this mechanism alters the synaptic coupling of
neurons and thus stimulus transmission and processing. If it is disrupted, disorders such as epilepsy, schizophrenia or autism may be the result. The findings are published in the journal Cell Reports.


========================================================================== Almost 100 billion nerve cells perform their service in the human
brain. Each of these has an average of 1,000 contacts with other
neurons. At these so- called synapses, information is passed on between
the nerve cells.

However, synapses are much more than simple wiring. This can already be
seen in their structure: They consist of a kind of transmitter device,
the presynapse, and a receiver structure, the postsynapse. Between them
lies the synaptic cleft. This is actually very narrow. Nevertheless, it prevents the electrical impulses from being easily transmitted. Instead,
the neurons in a sense shout their information to each other across
the gap.

For this purpose, the presynapse is triggered by incoming voltage pulses
to release certain neurotransmitters. These cross the synaptic cleft
and dock to specific "antennae" on the postsynaptic side. This causes
them to also trigger electrical pulses in the receiver cell. "However,
the amount of neurotransmitter released by the presynapse and the extent
to which the postsynapse responds to it are strictly regulated in the
brain," explains Prof.

Dr. Susanne Schoch McGovern of the Department of Neuropathology at
University Hospital Bonn.

Sophisticated control mechanisms For instance, certain synapses are strengthened during learning: Even a weak electrical stimulus from the transmitter neuron is then sufficient to trigger a strong response in the receiver cell. In contrast, little-used synapses atrophy. Furthermore, sophisticated control mechanisms prevent the electrical activity in the
brain from spreading too far -- or, conversely, from fading away too
quickly. "We also speak of synaptic homeostasis," explains Prof. Dr.

Dirk Dietrich from the Department of Neurosurgery at the University
Hospital.

"It ensures that brain activity is always within a healthy range."
However, the processes that maintain this balance are only partially understood. One mechanism by which the brain responds to long-lasting
changes in neuronal activity is known as homeostatic plasticity. "We have
now shown that a protein called RIM1 plays a key role in this process,"
says Schoch McGovern. RIM1 is clustered in the so-called "active zone"
of the presynapse - - the area where neurotransmitters are released.



==========================================================================
Like any protein, RIM1 consists of a large number of contiguous amino
acids.

The researchers have now shown that some of these amino acids
are linked by an enzyme to a chemical compound, a phosphate
group. Depending on which amino acid is modified in this way, the
presynapse can subsequently release more or less neurotransmitter. The phosphate groups form the "memory" of the synapses, so to speak, with
which they remember the current activity level. "In the presynapse, transmitter-filled vesicles stand ready to be fired like the arrows of
a taut bow," Dietrich says. "As soon as a voltage pulse comes in, they
are released at lightning speed. Phosphorylation changes the number of
these vesicles." Synapse calls with louder voice If the presynapse can
"fire" more vesicles as a result, its call across the synaptic cleft
becomes louder, figuratively speaking. If, on the other hand, the number
of vesicles decreases sharply due to changes in the phosphorylation
status of RIM1, the call is barely audible. "Which effect occurs depends
on the phosphorylated amino acid," says Dr. Johannes Alexander Mu"ller
of Schoch McGovern's research group. He shares lead authorship of the
study with his colleague Dr. Julia Betzin.

This means that the brain can presumably adjust the activity of individual synapses very precisely via RIM1. Another key role is played by the
enzyme SRPK2: It attaches the phosphate groups to the amino acids
of RIM1. However, there are also other players, such as enzymes that
remove the phosphate groups again if necessary. "We assume that there
is a whole network of enzymes that act on RIM1 and that these enzymes
also control each other's activity," Dietrich explains.

The synaptic balance is immensely important; if it is disrupted,
disorders such as epilepsy, but possibly also schizophrenia or autism
can be the result.

Interestingly, the genetic information for RIM1 is often altered in
people with these psychiatric disorders. This may mean that the RIM1
protein is less effective in them. "We now want to further elucidate
these relationships," says Schoch McGovern, who is also a member of
the Transdisciplinary Research Area "Life and Health." "Perhaps new
therapeutic options for these diseases will emerge from our findings
in the long term, although there is certainly a long way to go before
that happens." Participating institutions and funding The study was
supported by the German Research Foundation (DFG), the BONFOR program
of the University Hospital Bonn, the Australian National Health and
Medical Research Council (NHMRC), and the Cancer Research Foundation and
Cancer Institute New South Wales. In addition to the University and the University Hospital Bonn, the University of Sydney and the Australian
company i-Synapse were involved in the work.


========================================================================== Story Source: Materials provided by University_of_Bonn. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Johannes Alexander Mu"ller, Julia Betzin, Jorge Santos-Tejedor,
Annika
Mayer, Ana-Maria Oprişoreanu, Kasper Engholm-Keller, Isabelle
Paulussen, Polina Gulakova, Terrence Daniel McGovern, Lena Johanna
Gschossman, Eva Scho"nhense, Jesse R. Wark, Alf Lamprecht, Albert J.

Becker, Ashley J. Waardenberg, Mark E. Graham, Dirk Dietrich,
Susanne Schoch. A presynaptic phosphosignaling hub for lasting
homeostatic plasticity. Cell Reports, 2022; 39 (3): 110696 DOI:
10.1016/ j.celrep.2022.110696 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220420092134.htm

--- up 7 weeks, 2 days, 10 hours, 51 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)