NEUROEPIGENETIC CONTROL OF GAMMA OSCILLATIONS IN THE PEDUNCULOPONTINE NUCLEUS: FROM HDACs TO F ACTIN

URBANO FJ; BISAGNO V; GARCIA-RILL E

Daegu

Congreso; International Brain Research Organization Meeting; 2019

IBRO

Gamma oscillations in the pedunculopontine nucleus (part of the reticular activating system, are mediated by P/Q type Ca 2 channel activation and are affected by the balance between histone acetylation and deacetylation. Our previous work described how i acute 20 30 min) in vitro exposure to the histone deacetylase ( inhibitor trichostatin A ( led to the elimination of high threshold, voltage‐dependent Ca 2 channel‐mediated intrinsic gamma band membrane oscillations ii) pre‐incubation 60 90 min) with TSA led to a similar decrease specifically in gamma band oscillations, iii) a significant reduction in Ca2+ currentswas elicited by the same histone acetylation inhibitor, iv) a HDAC Class I inhibitor, MS 275 failed to affect intrinsic gamma oscillations in PPN neurons, and v) a HDAC Class IIa inhibitor, MC1568 blocked gamma oscillations (Urbano etal 2018 Sci Rep 8 13156). Here, we used in vivo i p administration of histonedeacetylase inhibitors followed by recordings of brain slices 4 hr later We observed that MC 1568 20 mg/Kg) blunted PPN cell ability to generate gamma oscillations, in a reversible manner Inhibition of class I histone deacetylases with MS 275 (20 mg/Kg) did not show any effects, while higher concentrations of MS 275 (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 Inaddition, 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, HDAC cytosolic activity, and processes related to gene transcription in the control of P/Q type Ca2+ channelmediated intrinsic PPN gamma oscillations This work was supported by grants from NIH award P 30 GM 110702 from the IDeA program at NIGMS to the CTN, grants fromFONCYT Agencia Nacional de Promoción Científica y Tecnológica Préstamo BID Nacional de Promoción Científica y Tecnológica Préstamo BID 1728 OC AR PICT 2015 2594 (to Dr Bisagno) and PICT‐ 2016 1728 (to Dr Urbano).