Masters thesis - The role of astrocytic Cl as modulator of E/I-balance

Background: Astrocytes are the primary homeostatic cells in the central nervous system (CNS), and one of their critical roles includes the regulation of extracellular ionic composition (ionostasis). Recently, we discovered that astrocytes serve as a dynamic reservoir for chloride (Cl-), significantly modulating inhibitory transmission that depends entirely on this anion. In a series of experiments involving awake, behaving mice, we observed that an increase in intracellular Cl- concentration in astrocytes ([Cl-]i) suppresses neuronal activity, while a decrease in astrocytic [Cl-]i enhances it. We provided evidence that this mechanism is mediated by Cl- efflux through GABAA receptors (GABAAR) expressed on astrocytes. Moreover, we found that astrocytic [Cl-]i is brain state-dependent, maintaining high and stable levels during sleep, and exhibiting dynamic, lower levels during wakefulness. These fluctuations in astrocytic chloride significantly influence the excitation/inhibition balance in both healthy and diseased brains.  Next, we will investigate the implications of modulating astrocytic Cl- on sleep architecture and in pathophysiological conditions such as epilepsy.

The position: We are looking for a Master student to complete our team and help us decipher the role of astrocytic Cl- as regulator of E/I balance in sleep architecture or pathophysiological conditions such as epilepsy. We are using a broad spectrum of state-of-the-art imaging and electrophysiology techniques in in vivo mouse experiments.

About the lab: You will be part of a young team, which was founded in Nov 2022. Our lab consists of a Postdoc, two PhD students and a research assistant. Our group is part of the Center for Translational Neuromedicine, which is part of SUND KU and located at Panum.

Your background: You are a highly motivated student with an interest in how the brain works. You are open and curious, eager to learn new techniques, a team player and interested in becoming a member of a young and dynamic, international team. Pre-requisites are good communications skills in English and a FELASA certificate.

Supervisors:

Verena Untiet, Assistant Professor/Group Leader, Center for Translational Neuromedicine, KU

Zuzanna Bojarowska, PhD Student, Center for Translational Neuromedicine, KU

Katharina Baumgart, PhD Studnet, Center for Translational Neuromedicine, KU

Relevant Literature:

Untiet V, Verkhratsky A (2024) How astrocytic chloride modulates brain states. Bioessays DOI: 10.1002/bies.202400004

Untiet V, Nedergaard M, Verkhratsky A (2024) Astrocyte chloride, excitatory-inhibitory balance and epilepsy. Neural Regen Res DOI: 10.4103/1673-5374.390981

Untiet V (2024) Astrocytic chloride regulates brain function in health and disease. Cell Ca DOI: 10.1016/j.ceca.2024.102855

Untiet et al. (2023) Astrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice. Nat Commun DOI: 0.1038/s41467-023-37433-9

Does this sound interesting to you? Just send an email to verena@sund.ku.dk and we schedule an informal meeting.