We study the mechanisms underlying the processes of learning and memory, at the molecular, cellular and systems level. Our current focus is on the immediate-early gene Arc, which plays an essential role in memory consolidation. We have shown that efficient Arc translation requires coincident activation of the NMDA receptor and fear/reward signaling pathways. We have localized Arc protein to the nucleus, where it associates with PML bodies, sites of epigenetic transcription regulation, and with Tip60, a histone-acetyltransferase implicated in Alzheimer’s disease, suggesting that Arc mediates formation of long term memories through epigenetic regulation of gene expression. A second project investigates how information is processed, encoded and stored in networks formed by neurons growing in vitro, using a combination of optogenetics and multi-electrode array recording techniques. These experiments have demonstrated that generic cortical microcircuits have fading and hidden memory processes, and are able to process complex spatio-temporal information. This optogenetic MEA platform allows us to investigate the molecular and physiological basis of disorders in memory, cognition, and perception. These projects are supported by an in silico drug development program which identifies small molecules with efficacy at therapeutic targets identified by our research program.
- Ju H, Dranias MR, Banumurthy G, and VanDongen AMJ, 2015, Spatio-temporal memory is an intrinsic property of networks of dissociated cortical neurons, J. Neurosci., 35:4040-4051.
- Dranias MR, Ju H, Rajaram E, and VanDongen AMJ, 2013, Short-term memory in networks of dissociated cortical neurons, J. Neurosci. 33: 1940-55.
- Wee CL, Teo S, Oey NE, Wright GD, VanDongen HMA and VanDongen AMJ, 2014, Nuclear Arc interacts with the histone acetyltransferase Tip60 to modify H4K12 acetylation, eNeuro 0019-14.2014
- Oey NE, Leung, H-W, Ezhilarasan E, Zhou L, Beuerman RW, VanDongen HMA, and VanDongen AMJ, 2015, A neuronal activity-dependent dual function chromatin-modifying complex regulates Arc expression, eNeuro 0020-14.2015.
- Dranias MR, Westover MB, Cash S, VanDongen AMJ, 2015, Stimulus information stored in lasting active and hidden network states is destroyed by network bursts, Front. Intergr. Neurosci. 9: 14.
- Bloomer WAC, VanDongen HMA and VanDongen AMJ (2008), Arc/Arg3.1 translation is controlled by convergent N-Methyl-D-aspartate and Gs-coupled receptor signaling pathways, J. Biol. Chem. 283: 582-592.
- Bloomer WAC, VanDongen HMA and VanDongen AMJ (2007), Activity-regulated cytoskeleton-associated protein Arc/Arg3.1 binds to spectrin and associates with nuclear promyelocytic leukemia (PML) bodies, Brain Res. 1153: 20-33.
- Van de Ven TJ, VanDongen HMA and VanDongen AMJ (2005), The non-kinase phorbol ester receptor α1-chimaerin binds the NMDA receptor NR2A subunit and regulates dendritic spine density, J. Neurosci. 25: 9488-9496.
- VanDongen AMJ (2004), K channel gating by an affinity-switching selectivity filter, Proc. Natl. Acad. Sci. USA 101: 3248-3252.
- Jones KS, VanDongen, HMA and VanDongen, AMJ (2002), The NMDA receptor M3 segment is a conserved transduction element coupling ligand binding to channel opening, J. Neurosci. 22: 2044-2053.