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Ryan
Remedios

Taming the autonomic nervous system

Dr. Ryan Remedios’ experimental work established the foundation for experience-driven functional changes in neuronal circuits that in turn determine nervous system functions. Remedios is one of the newly recruited Helmholtz Pioneer Campus Team Leaders at Helmholtz Pioneer Campus. Read here about his motivation and future ambitions.

Ryan 
Remedios

 

I have uncovered some surprising insights into the activity of a region deep in the brain – called the hypothalamus. It’s known that our life experiences shape our future behaviour. These are learned behaviours. Humans, like other social animals, learn to interact optimally with the environment, and the brain circuits involved in learning and memory are under heavy current investigation. Paradoxically, there is evidence, including the Nobel Prize winning work of Tinbergen, Lorenz and von Frisch, that certain behaviours are genetically encoded, and are performed without prior learning. These are known as instincts or innate behaviours. The brain circuits that control these behaviours were thought to be genetically encoded and organized during brain development.

I want to investigate systems-level nervous system function and further our knowledge of autonomic circuitry, as I have high hopes that a deeper understanding will lead to some revolutionary therapies. I am delighted to be the principal investigator of the Autonomous and Autonomic Systems Group at Helmholtz Pioneer Campus (HPC) since July 2018: here I have the complex infrastructures needed to advance my research in the dynamics of neuronal circuit plasticity.

One event is all it takes!

The amazing fact I was privileged to observe is that a brief behavioural trigger is all it takes to transform some neurons within a neuronal population into a stable neuronal ensemble with long-lasting implications: the behavioural patterns these circuits control, will be ingrained for a significant portion of a lifetime.

In the study published in Nature, my colleagues and I were exploring mouse social behaviours. I recorded the activity of hundreds of neurons within the hypothalamus in socially interacting mice and discovered an ensemble of neurons active in the presence of males and another active in the presence of females. However, socially inexperienced mice lacked such a separation of ensembles, and the neurons responded to males and females equally. Interestingly the first sexual experience, even if brief, was the trigger that provoked the formation and separation of the male- and female-specific ensembles. Once these ensembles formed, they remained separate and stable for many months.

Our observation that a brief social exposure can trigger a long-lasting functional change within a neuronal population – in my opinion – unlocks the door to an enigmatic universal mechanism. The benefits of uncovering the molecular and cellular mechanisms behind this phenomenon may allow us to control specific circuits and hence facilitate the development of a range of therapies for posttraumatic stress disorder, addiction or influence physiological ageing. Therapies that could reduce the deteriorating effects of ageing on autonomic system function will be a special focus of my new team. As human lifespans keep increasing, I would like for people to live long, with health and dignity!

 

Deeper insights into deep-brain function

To achieve these goals I am utilizing a bundle of complementary, cutting-edge technologies. I am a specialist in in vivo electrophysiology and in vivo calcium imaging, wherein I can record, and in the future manipulate, the activity of hundreds of neurons in freely moving and socially interacting mice. My expertise in micro-endoscopic calcium imaging brought recent success by recording the activity of populations of single neurons simultaneously with behaviour. My next objective is to simultaneously record neuronal activity, behaviour and multiple other physiological parameters such as changes in body temperature, heartrate, respiration, and determine how these change with ageing using different mouse models.

I am eager to share this knowledge and my lab’s expertise with my new colleagues in Munich and beyond. I am also looking forward to new avenues for collaboration, with biologists, chemists, physicists, computer scientists and just about anyone with a passion for uncovering the secrets of how the coordinated activity of neurons controls thought, physiology and behaviour. This collaborative, interdisciplinary culture is one of the reasons why I turned down other attractive offers from European institutions to take up a post at HPC. I was keen to find a place like the HPC, a nucleus attracting successful, inspiring, young scientists interested in collaborating on new ideas, an accomplished, yet young management, that encourages tackling risky, challenging topics for scientific leaps and breakthroughs rather than incremental advances, and the smorgasbord of techniques and technologies already available at the HMGU. I am convinced that bringing together experts from diverse fields helps stimulate inspiration: My ambitions as a neurophysiologist is accentuated by my enthusiastic team which includes an interdisciplinary mix of a medical doctor, a mechanical engineer, a physicist, a veterinarian and a neurobiologist.

Only through interdisciplinary collaboration we will be able to fully explore the nervous system in sufficient detail. This, in turn, will enable to reverse or alleviate the degenerative processes that affect us all through illness or just natural ageing.

Publication:
Remedios R, Kennedy A, Zelikowsky M, Grewe BF, Schnitzer MJ, Anderson DJ.: Social behaviour shapes hypothalamic neural ensemble representations of conspecific sex. Nature. 2017 Oct 18;550(7676):388-392. doi: 10.1038/nature23885.


Listen to the podcast

Brady Huggett talks with Ryan about the HPC PI’s research interests, career path and reasons for joining the HPC.