Manipulating the maturation of fast-spiking inhibitory neurons

The brain is composed of excitatory and inhibitory neurons which form complex brain circuits. Inhibitory neurons account for 10-20% of all neurons in the neocortex and are classified as interneurons. Despite this low percentage, interneurons are important during brain development as aberrant maturation is linked to numerous neurological diseases. For example, abnormal development of fast-spiking parvalbumin (PV) interneurons is linked to epilepsy. Interestingly, PV interneurons mature late during development compared to other interneurons. It is thus necessary to know why different interneurons undergo a distinct maturation program. Another reason to study interneuron maturation is that transplantation of interneuron progenitors or stem cell-derived PV+ interneurons can be used to restore the inhibitory balance in the neuronal network. However, these protocols take 7-8 months to complete, rendering them unsuitable for any use in drug discovery or cell replacement therapy. We need to understand the mechanisms behind the maturation process of PV interneurons in order to better comprehend their role in epilepsy.In this project, we will focus on mitochondria and their metabolism as they are important for the maturation of the fast-spiking activity of PV interneurons. Thus, we will manipulate mitochondrial dynamics during the maturation of PV interneurons. We will use techniques, such as in utero electroporation and neuron transplantation . This knowledge can be used to generate novel methods for cell-based therapies in neurological diseases.

Keywords:Interneuron development, Parvalbumin positive fast-spiking interneurons, Mitochondrial morphology and metabolism

Disciplines:Developmental neuroscience

Project type:PhD project