A defective potassium channel disrupts the brain's navigation system


Date:
August 16, 2021
Source:
University of Erlangen-Nuremberg
Summary:
The potassium channel KCNQ3 is required for our brain to generate
accurate spatial maps. In mice, defects in KCNQ3 function have
measurable effects on the internal navigation system.



FULL STORY ==========================================================================
The potassium channel KCNQ3 is required for our brain to generate
accurate spatial maps. In mice, defects in KCNQ3 function have measurable effects on the internal navigation system. The findings of a research
team including researchers from Friedrich-Alexander Universita"t Erlangen-Nu"rnberg (FAU) recently published in Nature Communications
are also relevant for Alzheimer's- type dementia research.


==========================================================================
In addition to other physiological processes, potassium is required
for muscle and nerve cell excitability. Potassium ions cross the outer
cell membrane via a variety of ion channels and thereby generate
electrical currents. Twenty years ago, Prof. Thomas Jentsch's team
at the Leibniz Research Institute for Molecular Pharmacology (FMP) in
Berlin identified the genes encoding the potassium channel family KCNQ2-5
and demonstrated that mutations in KCNQ2 and KCNQ3 can cause hereditary epilepsy in humans. Pharmaceutical companies were able to develop targeted anti-epileptic drugs as a result of this pioneering research.

Now, teams of molecular biologists led by Thomas Jentsch and
neurophysiologists supervised by Alexey Ponomarenko, professor at
the Institute of Physiology and Pathophysiology at FAU, together with scientists at the University of Conneticut (USA) and the University of
Cologne, have discovered that KCNQ3 may also play a role in Alzheimer's
disease and other cognitive disorders.

Precise navigation maps in the brain Normally, the transmitter
acetylcholine inhibits neuronal potassium flow, which is necessary for
cortical excitability and thus for memory and attention. It is well
established that Alzheimer's patients gradually lose this cholinergic neuromodulation.

The current study examined the role of KCNQ3 channels in the
neuromodulation of the brain's navigation system. These place fields,
a discovery for which a Nobel Prize was awarded several years ago, serve
as an internal map for the brain. 'We discovered how various signals
generated by place cells under the control of KCNQ3 channels interact
with brain rhythms to form precise spatial maps,' says Alexey Ponomarenko.

The knock-out mice with a defective KCNQ3 channel generated by Thomas
Jentsch's group revealed a different picture. Although the activity
patterns of place cells in healthy mice followed a specific temporal
and spatial pattern, in knock-out mice, the synaptic transmission
by single or nearly simultaneous multiple (burst) signals of place
cells was disorganised. 'When bursts are fired, they typically have a
certain rhythm. In the mutants, however, the bursts are not controlled
by the rhythm, but are fired at completely random times or phases of the rhythm,' explains Prof. Ponomarenko. ?This effectively suppresses single
action potentials and creates an imbalance in the activity patterns of
place cells.' Combined with optogenetic experiments, recordings using
silicon probes measuring 15 micrometers in thickness implanted in the hippocampus of freely behaving rodents, provided exciting insights into
brain function. Additionally, the team members in America demonstrated
that the absence of the KCNQ3 channel resulted in a significant decrease
in neuronal potassium currents (here M- currents).

'While there is insufficient data to date for clinical applications,
our findings suggest that the KCNQ3 channels could be a potential target
for future drug research to treat Alzheimer's and other dementias,'
emphasises Prof.

Ponomarenko, 'at least in the early stages, when place cells are
likely still present but cholinergic neuromodulation has already
subsided.' Additional research is required to gain a better understanding
of KCNQ3's role in the brain.

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


========================================================================== Journal Reference:
1. Xiaojie Gao, Franziska Bender, Heun Soh, Changwan Chen, Mahsa
Altafi,
Sebastian Schu"tze, Matthias Heidenreich, Maria Gorbati,
Mihaela-Anca Corbu, Marta Carus-Cadavieco, Tatiana Korotkova,
Anastasios V.

Tzingounis, Thomas J. Jentsch, Alexey Ponomarenko. Place fields
of single spikes in hippocampus involve Kcnq3 channel-dependent
entrainment of complex spike bursts. Nature Communications, 2021;
12 (1) DOI: 10.1038/ s41467-021-24805-2 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210816125720.htm

--- up 14 weeks, 3 days, 22 hours, 45 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)