Summary: The SLK protein plays a key role in the excitability and sensitivity of neurons, the researchers report.
Source: University of Bonn
Nerve cells can regulate their sensitivity to incoming signals autonomously. A new study from the University of Bonn has now discovered a mechanism that does just that. The German Center for Neurodegenerative Diseases and the Max Planck Institute for Behavioral Neurobiology were involved in the work.
The results have just been published in the journal Cell reports.
Anyone who’s ever sent a voicemail with a cell phone knows how important volume is: shouting into the microphone results in a distorted and unclear recording. But whispering is not a good idea either, the result is then too quiet and difficult to understand. That’s why sound engineers guarantee perfect sound at every concert and talk show: they adjust the gain of each microphone according to the input signal.
Neurons in the brain can also fine-tune their sensitivity, and even do so autonomously. A new study by the University of Bonn and the University Hospital Bonn shows how they do it. To this end, the participants studied the networks of nerve cells that also play a role in vision, hearing and touch.
The stimulus first travels to the so-called thalamus, a structure located in the center of the brain. From there it is then routed to the cerebral cortex, where it is further processed.
Each neuron adapts
“Neurons in the cerebral cortex are stimulated by signals from the thalamus to generate action potentials,” explains Professor Heinz Beck from the Institute for Experimental Epileptology and Cognitive Research at the University Hospital Bonn.
“These are short voltage pulses that are then transmitted to other sites in the brain. For this to work well, neurons must adapt to the intensity of excitatory signals.
For example, they must reduce their sensitivity if the incoming stimuli are very strong.
“We have now discovered that a specific enzyme called SLK plays a role in this process,” says Beck, who is also spokesperson for the transdisciplinary research area “Life and Health” at the University of Bonn.
“It allows neurons to individually calibrate their own excitability.” Which is a bit like not having a sound engineer: instead, the microphones would automatically adjust their sensitivity so that the recording wasn’t too quiet or over-amplified.
“In this mechanism, special nerve cells play an essential role, the so-called interneurons,” explains Dr. Pedro Royero of Beck’s research group. He obtained his doctorate with this study at the Max Planck International Graduate School and performed most of the experiments. Interneurons send inhibitory action potentials to excited neurons. Somehow they turn the knob which reduces their sensitivity.
“The SLK now determines to what extent this regulator can be adjusted by interneurons, i.e. the strength of their inhibitory effect.”
There are two different types of interneurons. Some are activated directly by incoming impulses from the thalamus. They already inhibit the neurons while these are simultaneously excited by the thalamus.
Another type, on the contrary, is activated only by the activity of neurons in the cerebral cortex, that is, the very neurons that they are supposed to subsequently inhibit. They are therefore part of a negative feedback loop.
“Interestingly, SLK is not active in this feedback inhibition, but only in the first case,” Royero points out.
New insights into disease development
The researchers were also able to show that certain genes are activated when adjusting sensitivity. They now want to investigate their role in the process in more detail. This is also interesting because the balance between excitation and inhibition is extremely important for brain function.
This is seen, for example, in epilepsy: the characteristic seizures result from over-excitation of large areas of nerve cells. In fact, studies show that in some epileptic patients, less SLK is found in neurons than normal. Perhaps the study will therefore also contribute to a better understanding of the mechanisms of these diseases.
About this neuroscience research news
Author: Press office
Source: University of Bonn
Contact: Press office – University of Bonn
Image: Image is in public domain
Original research: Free access.
“Circuit-selective cell-autonomous regulation of inhibition in pyramidal neurons by Ste20-like kinase” by Heinz Beck et al. Cell reports
Circuit-selective cell-autonomous regulation of inhibition in pyramidal neurons by Ste20-like kinase
- SLK regulates excitation-inhibition balance autonomously
- SLK in cortical neurons regulates anticipation but not feedback inhibition
- SLK selectively regulates inhibition by parvalbumin-expressing interneurons
Maintaining an appropriate balance between excitation and inhibition is essential for neural information processing. Cortical neurons can autonomously adjust the inhibition they receive to individual levels of excitatory input, but the underlying mechanisms are unclear.
We describe that the Ste20-like kinase (SLK) mediates cell-autonomous regulation of the excitation-inhibition balance in the thalamocortical feedforward circuit, but not in the feedback circuit.
This effect is due to the regulation of inhibition originating from interneurons expressing parvalbumin, while inhibition via interneurons expressing somatostatin is unaffected. Computational modeling shows that this mechanism promotes stable excitatory-inhibitory relationships in pyramidal cells and ensures robust and sparse coding.
Patch-clamp RNA sequencing yields genes differentially regulated by SLK inactivation, as well as genes associated with excitation-inhibition balance involved in transsynaptic communication and cytoskeletal dynamics.
These data identify a cell-autonomous regulatory mechanism of a specific inhibitory circuit that is essential to ensure that a majority of cortical pyramidal cells participate in information coding.
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