Functionally repairing complex synaptic circuitry

The complexity of neuronal circuits presents a challenge when investigating potential future treatments for diseases caused by central nervous system defects. In a highly collaborative study from three groups at Harvard Medical School, Czupryn et al. show that transplanted neurons can establish neuronal circuitry in the mouse hypothalamus. This brain region controls aspects of whole-body metabolism, such as satiety and energy expenditure, in part by interpreting signals from the adipocyte-derived hormone leptin. To assess the potential to functionally repair complex neuronal circuitry, the authors transplanted fluorescently labelled leptin-responsive immature neurons and progenitors into db/db mice (which lack the leptin receptor, and are thus severely diabetic and morbidly obese). The transplanted cells localised to the hypothalamus, differentiated into the appropriate neuronal subtypes necessary for leptin signalling, functionally integrated, and led to amelioration of obesity and hyperglycemia. Thus, transplanted neurons can establish complex neural circuitry and restore defective physiological functions, suggesting great therapeutic potential for selected nervous system diseases.