"We are delighted for Rohini Kuner and Hannah Monyer," says Michael Boutros, Dean of the Medical Faculty Heidelberg and member of the Executive Board of Heidelberg University Hospital. "The ERC is one of the most highly endowed and recognized scientific awards. The fact that two of our members have received it this year shows how outstanding Heidelberg is in the field of medicine."

Not all pain is the same

How we evaluate pain depends, among other things, on the situation, experiences or fears. This "mixed situation" is reflected in an almost confusing interconnection of the relevant nerve pathways in the brain. Over the next five years, Rohini Kuner, Managing Director of the Institute of Pharmacology at the Medical Faculty of Heidelberg University, and her team would like to investigate how the cellular networks of pain processing differ from those of other sensory perceptions and cognitive functions, how they are influenced by them and, above all, what changes in chronic pain and how this can be reversed.

"Despite important findings in recent years, the conditions under which pain becomes chronic are still an unsolved mystery. There are still too many pieces of the puzzle missing to understand the overall picture," explains Kuner, who was awarded the Leibniz Prize by the German Research Foundation just last year. In the PAIN ENSEMBLES project that is now being funded, she wants to look beyond the pain-processing networks in the cerebral cortex and find out how sensory perceptions, sensations and experiences influence them and thus possibly contribute to the perpetuation of pain. "We still don't know enough about how pain differs from other sensory perceptions and feelings at the cellular level. At the same time, we hardly understand how psychological, social and environmental influences permanently change the networks and mechanisms of pain processing," says Kuner.

First understand, then reverse

Kuner assumes that certain nerve cell networks in the cerebral cortex, which are structurally and functionally interconnected, serve to classify and evaluate pain.

Depending on the context and current condition of the living being, this could enable flexible adaptation mechanisms and in this way also incorporate previous pain experiences, fear memory and expectations. The aim is to identify those cell networks that separate pain from other perceptions and influences and to find out how these are composed and networked with each other. "Above all, we want to see how these cell ensembles change when acute pain turns into chronic pain and whether expectation and fear memory promote chronification," says Kuner. Building on these results, Kuner and her team will investigate whether the altered nerve cell circuits can be reversed by non-invasive neurostimulation and behavioral approaches, thereby alleviating chronic pain. State-of-the-art microscopic techniques such as multiphoton imaging of living nerve tissue, electrophysiological activity measurements of neuronal networks, genetic single-cell analyses and detailed behavioral analyses in mice will be used for this purpose.

Rohini Kuner can look back on many years of successful research achievements: she was awarded an ERC Advanced Grant in 2011 and is currently the spokesperson for the Collaborative Research Centre "From nociception to chronic pain: structure-function characteristics of neural pathways and their reorganization" (SFB 1158), which is coordinated from Heidelberg; just a few weeks ago, she received the Leibniz Prize from the DFG. As Dean of Research, she also supports the internal research and early career support measures at Medical Faculty Heidelberg.

Pacemaker cells in the brain control memory

The hippocampus is the area of the cerebrum where new memory content is created. The activity of the hippocampus is controlled by a small region of the brain known as the septum. Certain inhibitory neurons of the septum are considered "pacemaker cells": they extend into the structures of the hippocampus, where they synchronize the activity of neuronal ensembles and enable cognitive performance. Hannah Monyer has evidence that the septal neurons are associated with the development of neurodegenerative diseases. When these neurons are damaged, spatial memory and episodic memory (i.e. what, when, where) are impaired. In various animal models of neurodegenerative diseases, an increased sensitivity of the septal neurons has been observed. They are considered to be very "susceptible to disruption" because they fire at a high rate and are therefore extremely hungry for energy. There are indications that damage to the energy-producing mitochondria is behind this susceptibility.

New approach to the treatment of neurodegenerative diseases

In her project, funded by the ERC with two million euros over four years, Monyer wants to investigate how a loss of function of the septal neurons affects memory formation in the downstream hippocampus and which cellular mechanisms are behind this. What makes the septal neurons so vulnerable? Is it really mitochondrial defects? Monyer and her team want to find out what role these special neurons play in the symptoms in the early stages of neurodegenerative diseases and could therefore represent a possible new starting point for therapeutic interventions.

Hannah Monyer heads the Clinical Neurobiology Department, which is based at both the DKFZ and Heidelberg University Hospital. The neuroscientist has already received numerous awards, including the Leibniz Prize in 2004. In 1999, she received the Order of Merit of the Federal Republic of Germany. The ERC had already awarded her an Advanced Grant in 2010, and in 2020 she received the Lautenschläger Research Prize.

For top researchers who want to open up new areas of research

The European Research Council (ERC), founded by the European Union in 2007, is the most important European funding organization for excellent frontier research. It funds researchers of all nationalities who are carrying out projects throughout Europe. The ERC Advanced Grants support established top researchers with an outstanding scientific track record over the last ten years who wish to explore new areas of research.

Contact

Professor Dr. Rohini Kuner 
Director
Pharmacological Institute at Medical Faculty Heidelberg
Heidelberg University

rohini.kuner@pharma.uni-heidelberg.de

Prof. Dr. Hannah Monyer
Director
Cooperation Department Clinical Neurobiology at German Cancer Research Center and Heidelberg University Hospital
Medical Faculty Heidelberg
Heidelberg University

h.monyer@dkfz.de