Molecular architecture underlying super-sensitivity of dopamine D1 receptor expressing neurons in striatum

Neuronal plasticity and transcriptional activity in a sparse ensemble of neurons are central to learning and memory formation.

The recent observations that dopamine (DA) D1-like receptor expressing neurons in the striatum are heterogeneous in their sensitivity to DA stimulation promises to shed light on how neurons are assigned to these ensembles.

To better understand the molecular mechanisms underpinning this phenomenon, the DA sensitivity of individual neurons will be correlated to their signaling signature, molecular organization and transcriptional profile.

To achieve this, we will first map the DA sensitivity of individual primary neurons and then (1) have them express different biosensors and monitor their signaling profile after DA stimulation, (2) investigate the “signaling interactome” of these cells with super-resolution microscopy and (3) use mRNA single-cell sequencing to map their transcriptional profile.

The project will be coordinated and managed independently by me in close collaboration with people in the group at the host university abroad, especially in the beginning but also continuously during the project.

This project will widen our understanding and appreciation of individual neurons’ function in the DA system and pave the way towards better disease understanding and treatment strategies of e.g. addiction and Parkinson’s disease. Additionally, it will bring important knowledge of molecular mechanisms central for learning and memory formation.