Inhibitory circuits and transmission in the hypothalamus in a mouse model of PWS

The genetic disorder Prader-Willi syndrome (PWS), results in debilitating physical, endocrine, cognitive, and behavioral symptoms. Many of the characteristics of PWS, such as uncontrollable food intake, stunted growth, and emotional problems suggest that disruptions in brain regions such as the hypothalamus may cause this. Recently, the gene Magel2 was shown to be associated with PWS symptoms. Magel2 is expressed in brain regions such as the hypothalamus, but the precise cells types that express this gene are unknown. In addition it is not known if loss of Magel2 leads to alterations in neural activity. Here, we hypothesize that Magel2 is expressed primarily in inhibitory neurons in the hypothalamus and extended amygdala, and that disruptions of the Magel2 gene leads to pathological inhibitory neurotransmission that promotes behavioral and physiological characteristics of PWS. Collectively, this work will identify novel and critical neurocircuit connections and cellular alterations that may occur in PWS. With data generated from these experiments, we will be able to identify precise neurocircuit targets for the development of novel treatment strategies for PWS.

Research Outcomes:

Functional circuit mapping of striatal output nuclei using simultaneous deep brain stimulation and fMRI. Van Den Berge N, Albaugh DL, Salzwedel A, Vanhove C, Van Holen R, Gao W, Stuber GD, Ian Shih YY. NeuroImage, 2017 Feb 1;146:1050-1061.

 

Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens. Albaugh DL, Salzwedel A, Van Den Berge N, Gao W, Stuber GD, Shih YY.  Scientific Reports. 2016 Sep 7;6:31613.

 

Lateral hypothalamic circuits for feeding and reward. Stuber GD, Wise RA. Nature Neuroscience. 2016 Jan 27;19(2):198-205

 

Lateral Hypothalamic Area Glutamatergic Neurons and Their Projections to the Lateral Habenula Regulate Feeding and Reward. Stamatakis AM, Van Swieten M, Basiri ML, Blair GA, Kantak P, Stuber GD. Journal of Neuroscience. 2016 Jan 13;36(2):302-11. 

 

Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors. Jennings JH, Ung RL, Resendez SL, Stamatakis AM, Taylor JG, Huang J, Veleta K, Kantak PA, Aita M, Shilling-Scrivo K, Ramakrishnan C, Deisseroth K, Otte S, Stuber GD.  Cell, 2015 Jan 29;160(3):516-27.