Event Abstract Back to Event Restorative Effects of the TrkB agonist 7,8-Dihydroxyflavone on Neuronal Network Activity in an in vitro model of Huntington's disease Alberto Capurro1*, Pablo Baliño1, Candise Baez1, Ayaka Sano2 and Ruth Luthi-Carter1 1 University of Leicester, Department of Neuroscience, Psychology and Behavior, United Kingdom 2 Hokkaido University, Japan Motivation Impaired transcription and transport of brain-derived neurotrophic factor (BDNF) have been strongly implicated in the pathogenesis of HuntingtonÕs disease (HD) [1,2]. Here we assess the possibility that the TrkB agonist 7,8-Dihydroxyflavone (7,8-DHF) [3] rescues HD-related changes in neuronal activity. Methods We compared micro-electrode array (MEA) recordings of a cellular model of HD comprised of rat P0 cortical neurons transfected with lentiviral vectors encoding an 171 aa fragment of either a normal (N171-18Q, 18Q) protein or disease-causing mutant (N171-82Q, 82Q) human Huntingtin protein [2]. The spike detection and data analyses were performed with customized R and Matlab codes run using the cluster machine of Leicester University (ÒAliceÓ). Results Population spike time histograms of selected examples of MEA recordings are shown in Fig. 1. They were examined together with their corresponding raster plots. Statistical comparisons of the three groups (18Q and 82Q with N = 7 MEAs, and 82Q+7,8-DHF with N = 4 MEAs) are depicted in Fig. 2. We confirmed previous results showing that the number and size of population bursts (PBs) decreases in 82Q cells. Moreover we show that treatment with the TrkB agonist 7,8-Dihydroxyflavone (7,8-DHF) can partially rescue the abnormal electrophysiological phenotype of 82Q cells, as has been previously shown in studies with BDNF. 82Q cells showed decreased spike counts, decreased burst numbers and burst intensities (Hz x active channels) and decreased mean correlation between the channels. 7,8-DHF treatment (50 nM) restored the spike counts and burst numbers (Fig. 2). Discussion and Conclusions This study confirmed our labÕs previous data showing that the number and size of PBs decreases in 82Q cells when compared to control (18Q) cells. Treatment with 7,8-DHF can significantly rescue the abnormal electrophysiological phenotypes of 82Q cells, showing an effect size similar to BDNF. Our results highlight the utility of MEAs as an in vitro model for studying HD, and indicate that 7,8-DHF or other TrkB agonists may have potential as HD treatments that restore synaptic connectivity in abnormal neuronal circuits. To further assess the role of connection probability and synaptic weight on the bursting behavior we will perform numerical simulations of randomly connected neural networks with excitatory and inhibitory neurons including adaptation using NEST (http://www.nest-initiative.org/). Acknowledgements The authors thank Dr Sandro Perrone for useful comments regarding data analysis. Supported by European CommissionÕs Seventh Framework Program FP7-PEOPLE-2011-IAPP project number 286403 Ð NEUROACT.