Schonewille Lab

Department                            Neuroscience

Principal investigator          Martijn Schonewille

E-mail address                      m.schonewille@erasmusmc.nl

Website                                     www.neuro.nl/research/schonewille

When you lose all inhibition: interneuron dysfunction in brain development

Supervisor: Catarina Osorio, c.osorio@erasmusmc.nl

Inhibitory interneurons are a large, diverse group of neurons important for fine-tuning neuronal circuits. Hence, errors in interneuron development lead to defects in circuit formation, resulting in several neurological disorders such as autism, schizophrenia, epilepsy, or attention-deficit/hyperactivity disorder (Levitt et al., Trends Neurosci. 2004; Di Cristo, Clin Genet. 2007, Marin, Nat Rev Neurosci. 2012). A central question remains unanswered: how do different subtypes of interneurons contribute to circuitry formation and their specific role in brain function? While the interneuron role in circuit formation has been extensively explored in the neocortex, less attention has been given to the inhibitory GABAergic interneurons in the cerebellar cortex, particularly molecular layer interneurons (MLIs). Purkinje cells are the principal neurons in the cerebellar cortex, and they rely on the input of MLIs to regulate a variety of behaviors. Interestingly, cerebellar interneurons, like basket cells and stellate cells, migrate and differentiate at different time points. Both basket cells, and stellate cells are electrically active at early postnatal ages, but how loss of inhibitory activity influences the development of the cerebellum circuit.

Research Question: How does the electric activity of inhibitory interneurons influence the early formation of cerebellar circuitry? This question is at the heart of our research, as it holds the key to understanding the intricate process of brain development.

Further reading (click to link to article)

Purkinje cell intrinsic activity shapes cerebellar development and function

How neurons control movement: optogenetic stimulation during brace conditioning

This project aims to built and use the tools to combine a novel task, brace conditioning, with selective activation of specific neurons. For Brace conditioning a mouse is placed on a wheel, and presented with either only an LED light flash, or a light flash followed by a small movement of the wheel. Over time the mouse will learn to brace for the movement when the light is flashed. Optogenetic experiments will teach us which neurons are responsible for what part of the bracing movement. The goal in this project is to built the hardware and software controls to combine brace conditioning and optogenetic stimulation. A research technician or PhD student will perform the mouse handling parts.

Further reading (click to link to article)

Purkinje cell microzones mediate distinct kinematics of a single movement