Orexinergic modulation of neural resource

A07

We all know it – too little sleep or jet lag after a flight impairs our ability to think and remember because the internal rhythm of our brain gets confused. We are investigating how this inner rhythm and an important messenger substance for these processes, orexin, can be used to restore cognitive performance.

Principal Investigators

CRC 1436 member Anne Albrecht

Prof. Dr. Dr. med. Anne Albrecht

CRC 1436 member Oliver Stork

Prof. Dr. Oliver Stork

Prof. Dr. Dr. med. Anne Albrecht

Anne Albrecht is the head of the Department of Neuroanatomy at the Institute of Anatomy at the Otto-von-Guericke University. Her research group studies the functional neuroanatomy of emotional memory and stress adaptation circuits. She also teaches anatomy to 1st and 2nd year medical students.

The focus of her research is on the investigation of GABAergic interneurons and neuropeptides in learning, memory and stress processing in rodent models. To analyze the role of e.g. orexin in circuits of memory formation, her group uses neuronal tracing, high-resolution methods for expression analysis (RNAScope, laser-assisted microdissection & qPCR) as well as viral and pharmacological interventions in conjunction with behavioral analysis in mice and structural and molecular studies in cell and tissue cultures.

Institut:Otto von Guericke University Magdeburg, Medical Faculty

Project Title:A07 Orexinerge Modulation neuraler Ressourcen

Prof. Dr. Oliver Stork

Prof. Dr. Oliver Stork is head of the Department of Genetics & Molecular Neurobiology at the Institute of Biology at the Otto von Guericke University Magdeburg. His research is devoted to understanding molecular and cellular mechanisms underlying the formation and specification of emotional memories. His special focus is on the analysis of local circuit processes in the context of the formation of engram cell assemblies in the hippocampus. He will contribute his expertise in the establishment and integrative analysis of rodent models for behavioral and memory research to the CRC.

In addition to the SFB1436, Prof. Stork is a member of the Magdeburg Collaborative Research Center SFB854 and the German Center for Mental Health in Magdeburg, and serves as a spokesperson for various neuroscientific graduate schools, including the IRTG1436 (this program), the CBBS graduate program and the GRK2413 (deputy spokesperson).

Institut:Otto von Guericke University Magdeburg, Faculty of Natural Sciences

Project Title:A07 Orexinergic modulation of neural resource

:Z01 Functional neural circuit analysis and small animal imaging in vivo

:ITRG

Co-Workers

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Lara Barreira

CRC 1436 member Gürsel Caliskan

Dr. Gürsel Caliskan

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Dr. Yunus Demiray

CRC 1436 member Hannah Gapp

Hannah Gapp

CRC 1436 member Harini Srinivasan

Harini Srinivasan

CRC 1436 member Alice Weiglein

Dr. Alice Weiglein

Lara Barreira

I am a Ph.D. student at the Institute of Anatomy. I am interested in the mechanisms that allow cognitive flexibility to incorporate and integrate environmental information into learning and memory. Within the framework of the A07 project, I study how circadian rhythms modulate cognitive functions. I am focused on researching how orexinergic neurons modulate the wakefulness system. For this purpose, I am using circadian disturbances, pharmacological tools, viral interventions, memory tests, and behavioral tasks.

Dr. Gürsel Caliskan

I have been studying cellular and circuit-level changes in animal models of fear and anxiety via combining electrophysiology, behaviour and pharmacogenetics (DREADDs). My current research focuses on identification of physiological and pathological alterations in the hippocampal activity patterns and their relation to modulation of hippocampal engrams in animal models of neuropsychiatric and neurodegenerative disorders. I am also interested in the impact of gut microbiota on hippocampal plasticity and oscillations.

Dr. Yunus Demiray

coming soon

Harini Srinivasan

I am a PhD student in the SFB 1436 since August 2021. I work under the sub project Orexinergic Modulation of neural resource (A07), where I study how memory engrams are modulated by the circadian rhythm. I focus on how orexinergic signalling plays a role in this modulation by using behavioural, molecular and biochemical techniques. After my Bachelor’s degree in Biotechnology, I graduated from OVGU with Master’s in Integrative Neuroscience. During my master thesis, I studied in vitro how intracellular calcium is regulated by Neuroplastin-PMCA complex in hippocampal neurons.

Dr. Alice Weiglein

Currently, I am working as a postdoc in the Albrecht Lab for Functional Neuroanatomy of stress and emotional learning. During my education as a neurobiologist, I investigated mechanisms of reinforcement learning in small animal models. To that end, I am now involved in different projects in which we investigate hippocampal circuits involved in learning and memory, as well as mechanisms of stress adaptation, autophagy mechanisms in stress-induced pathologies, and stress-induced disturbances of the skin-brain axis in murine models.

What is the orexin?

Orexin is a small neuropeptide. It is produced in a few cells in the hypothalamus, our control center in the brain for autonomic functions such as sleeping, eating and reproduction. Orexin acts there as the most important wake promoting factor. Orexin may also affect memory formation and cognitive flexibility by connecting the hypothalamus to other brain areas such as the hippocampus and the prefrontal cortex in the frontal lobe.

What is the joint function of the hippocampus and prefrontal cortex?

Both brain areas work closely together to retrieve memory content or to apply what has already been learned in a new context (cognitive flexibility). While the hippocampus sends direct neuronal connections to the prefrontal cortex, further intermediate stations are switched on in the “return path”, such as the so-called supramammillary nucleus (Vertes, 2015). Information processing also takes place in these intermediate stations (Hashimotondani et al., 2018), but it is not yet clear how orexin influences the flow of information between all these brain areas.

How does orexin work in the hippocampus and prefrontal cortex?

The hippocampus, supramammillary nuclei, and prefrontal cortex receive orexin signals from the hypothalamus and sense them with receptors for orexin on their cells. Pharmacological studies have shown that the stimulation of such orexin receptors supports neuronal plasticity and spatial memory formation (Akbari et al., 2010; Dang et al., 2018). The stimulation of the orexin receptors can trigger molecular changes in these cells and thereby support their permanent connection. This contributes to the formation of a kind of memory trace in the brain.

The goals of our project

We will investigate how disturbances of the circadian rhythm affect the information flow between the prefrontal cortex and the hippocampus influences it and will analyse the role orexin and its receptors play in these processes. We are also interested in how orexin influences the cellular and molecular processes in the hippocampus that enable neuronal cells to be linked to memory traces.

Orexin in cognition circuits 

We use viral neuronal tracers to map connections between the prefrontal cortex, supramammillary nucleus, and hippocampus. In order to find out whether the interconnected nerve cells contain orexin receptors, they are isolated using laser microdissection and their mRNA profile is examined. In addition, we use the RNAScope technique to display the expression of orexin receptors in the individual brain areas with high spatial resolution.

Orexin action in the hippocampus

We will investigate how a disruption of the circadian rhythm (disrupted sleep, jet lag) affects learning and memory and which role the hippocampus, supramammillary nuclei and prefrontal cortex play in these processes. We will also evaluate the impact of the local reduction of orexin receptors on learning and memory. Then we will test how the intranasal application of orexin and, as a complement, a blockade of orexin receptors affects cognitive performance and the formation of cellular memory traces in the hippocampus.

A glimpse into the future

We expect, together with other SFB projects, to gain insights into neuronal circuits and cellular mechanisms that can counteract cognitive decline. Orexin has great potential not only to improve cognitive performance after circadian rhythm disturbances, but also to counteract the loss of such neuronal resources during stress or aging processes. Since orexin can also be used in humans as a nasal spray or orexin blocker as a sleeping pill, new therapeutic approaches for patient groups with sleep disorders, anxiety disorders or various forms of dementia can arise in the long run.

Publications of the project A07