Ágata Silván. Investigating the excitation/inhibition (E/I) imbalance hypothesis of neuropsychiatric disorders in the cortico-thalamic system with electrophysiological methods


Schizophrenia is associated with abnormal inhibitory control in the circuit linking cortex and thalamus. Imbalances in the processing of sensory input may impair both memory and cognition. In particular, the sleep spindle activity that is driven by the reticular nucleus of the thalamus has been reported to be reduced in schizophrenic patients and suggested to be an endophenotype of schizophrenia (Merikanto et al. 2019).

Research Challenge

This project will focus on the interplay between E/I neurons in the cortico-thalamic network. Using a variety of electrophysiological methods and pharmacological tools, the E/I balance will be studied in both brain slices and awake and freely moving rodents. Specifically, the role of a series of ion-channels involved in pacing activity in the cortico-thalamic network will be studied. With access to both reduced (slice) and intact (freely moving) systems, the PhD student gets a unique opportunity to study E/I-mechanisms at a broad range of levels. The ultimate goal is to advance our understanding of the importance of upholding an E/I balance in the cortico-thalamic system and study both single neurons as well as population activity also measurable and impaired in patients.

Lundbeck‘s R&D organization is international and consists of more than 800 dedicated R&D staff, notably Dr. Kjartan Frisch Herrik, whose work has been focusing on synaptic transmission in vivo. The company’s research strategy aims at enabling the discovery and development of new pharmaceuticals targeting the underlying mechanisms of brain diseases.

Supervision and Secondments

The PhD project will be carried at Lundbeck’s Neuroscience R&D with Kjartan Herrik. The ESR will enrol in the Graduate Program in Neuroscience of the University of Copenhagen. The project also features secondments (extended stays) at EPFL (Carmen Sandi) and CIP-UEDIN (Peter Kind and Emily Osterweil).

Supervisors: Kjartan Frisch Herrik (KFH@Lundbeck.com), Charlotte Hougaard

Host Location: H. Lundbeck A/S, Copenhagen, Denmark.

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