Distinguished Lecture Series “Neuroepigenetics of arousal: F-actin control gamma oscillations in the pedunculopontine nucleus.” Francisco J. Urbano, Ph.D. Associate Professor Universidad de Buenos Aires Buenos Aires, Argentina Center for Translational Neuroscience Distinguished Lecture Series Tuesday, April 2, 12 noon Rayford Auditorium, Biomed II Bldg.

Our previous in vitro work determined that pedunculopontine neurons (PPN), part of the reticular activating system, required the activation of class IIa histone deacetylase in order to manifest P/Q-type Ca2+ channel-mediated intrinsic gamma oscillations. However, are these effects present in vivo? Here, we used in vivo (i.p.) administration of histone deacetylase inhibitors followed by recordings of brain slices 4 hr later. We observed that MC1568 (20mg/Kg), an inhibitor of class IIa histone deacetylases, blunted PPN cell ability to generate gamma oscillations, in a reversible manner. Inhibition of class I histone deacetylases with MS275 (20 mg/Kg) did not show any effects, while higher concentrations of MS275 (100 mg/Kg) enhanced PPN gamma rhythmicity. These results suggest the existence of a fine balance between HDAC I and HDAC IIa in PPN cells. Shifting the equilibrium towards lower activation of HDAC class IIa blocked gamma oscillations. On the other hand, shifting it towards lower HDACs class I enhanced gamma band oscillations of PPN neurons. In addition, we have new data suggesting that F-actin polymerization/depolymerization control gamma oscillations in PPN neurons depending on the level of HDAC activation. In conclusion, our results showed new links between F-actin cytoskeleton, HDACs cytosolic activity, and processes related to gene transcription in the control of intrinsic PPN gamma oscillations.