Neuropeptides

My laboratory uses primarily patch clamp electrophysiology in acutely-prepared brain slices from rat, mouse and human to study the actions of neuropeptides. The research is related to several human disorders, primarily including obesity, involuntary weight loss (cachexia/anorexia) and anxiety disorders such as post traumatic stress disorder (PTSD).

The Kurrasch Lab studies how hypothalamic neurons become organized into distinct neuronal clusters (“nuclei”). The human brain is exquisitely organized into either distinct layers or defined nuclei. Although layer formation has been well studied, comparatively little is known about the cellular and molecular mechanisms that guide the movement of neurons into nuclei. We use our unique collection of molecular markers and genetic tools to study how neurons that reside in one nucleus of the hypothalamus – the ventromedial nucleus (VMH) – are born and move to their final position. Presumably, similar mechanisms are used throughout the brain to organize neurons into clusters and thus, we predict that our findings in the VMH will be applicable to other brain regions. The long-term goal of the Kurrasch Lab is to explore whether environmental insults interfere with the developmental steps guiding hypothalamic nuclei formation, as an entry-point towards understanding the etiology of neuroendocrine disorders that are becoming increasingly common within the general population.

We currently are focused on three questions:

1. How does the VMH territory become specified? The hypothalamus consists of a dozen individual nuclei. What intrinsic (i.e., homeodomain transcription factors) and extrinsic (i.e., morphogens) factors drive specification of the zone that will become the VMH?
2. How does VMH neuronal diversity arise? What downstream factors are responsible for generating the specialized VMH cell types that arise from a seemingly homogeneous VMH progenitor pool?
3. How do newly-born VMH neurons migrate away from the ventricular zone to their exact position within the mature nucleus. How do they know where to go and when to stop?

To address these questions, we conduct loss-of-function (i.e., morpholino knockdown and Cre technology) and gain-of-function experiments (i.e., in utero electroporation) using both mice and zebrafish as model systems.