Functional analysis of the corticostriatal motor pathway at the single-cell level

The striatum is critical for the appropriate execution of movements and its dysfunctions cause severe motor disorders like Parkinson’s Disease.

Cortical inputs activate medium spiny neurons in striatum, which in turn initiate purposeful movements and suppress competing motor programs. Strikingly, the activation of single cortical neurons can initiate motor behaviour.

Yet, the selectivity, strength, and spatiotemporal properties of single cortico-striatal connections are unknown due to technical barriers.

To address these gaps in knowledge, I will develop a novel method allowing studies on individual long-range connections in the brain.

This approach is based on the combination of in vivo single-cell electroporation (SCE), optogenetics and patch-clamp electrophysiology.

Together, these methods enable the expression of light-sensitive opsins in individual cortical neurons that can be driven while recording from striatal neurons. Additionally, I will use whole-brain 2-photon tomography to image the anatomical organisation of individual axons. In total, two years will be spent in the foreign host lab, which is world-leading in SCE and imaging.

The remaining year will be spent in the Swedish host lab which possesses unique expertise in multi-neuron electrophysiological recordings.

This study will provide an innovative new tool for studying the functional communication between remote brain areas and will reveal single-cell mechanisms underlying cortico-striatal signal transmission.