Washington: Researchers have made a new breakthrough that could help explain why we feel hungry.
In this new paper, first authors Michael Krashes, PhD, and Bhavik Shah, PhD, postdoctoral fellows in the lab of Bradford Lowell , MD, PhD, Beth Israel Deaconess Medical Center (BIDMC) neuroendocrinologist, employed rabies circuit mapping, a technology in which a modified version of the rabies virus is engineered to "infect" just one type of neuron - in this case, the AgRP neurons that drive hunger.
The virus moves upstream one synapse and identifies all neurons that are providing input to AgRP starter neurons. Then, using a host of different neuron-specific cre-recombinase expressing mice (a group of genetically engineered animals originally developed in the Lowell lab) the investigators were able to map inputs to just these nerve cells, and then manipulate these upstream neurons so that they could be targeted
With this new information, the investigators now had a model to pursue.
Their results revealed that subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cylcase-activating polypeptide (PACAP) were in on the neuronal chatter.
Finally, through a chemogenetic technique known as DREADDs - Designer Receptor Exclusively Activated by Designer Drug - the authors used chemicals to specifically and selectively stimulate or inhibit these upstream neurons in the animal models.
The fed mice, which had already consumed their daily meal and otherwise had no interest in food, proceeded to search out and voraciously eat after DREADD stimulation. Conversely, the fasting mice - which should have been hungry after a period of no food - ate very little when these upstream neurons were turned off.
The study has been published online in the journal Nature.
