个人简介

B.A. (Psychology: Brock University) Ph.D. (Psychology: Behavioural Neuroscience, Brock University) Postdoctoral fellowship (Neurobiology: University of Alabama at Birmingham)

研究领域

Behavioural neuroscience neurobiology learning and memory fear conditioning systems consolidation plasticity epigenetics histone variant exchange chromatin rodents

My research focuses on the neurobiological mechanisms through which transient experiences produce persistent behavioral outcomes. Memory formation is a primary example of a general phenomenon in behavioural science, whereby transient life experiences are transformed to produce long-lasting changes in the brain, and ultimately, in behaviour. Epigenetic mechanisms, which provide a bridge between environmental stimuli and gene regulation, have the potential to act as stable molecular marks required to support memory formation and maintenance over a lifetime. Epigenetic modifications regulate access to DNA, which is obscured by its packaging into nucleosomes that consist of two each of histones H2A, H2B, H3, and H4. Nucleosome composition can be altered through the exchange of canonical histones with their replication-independent variants that differentially regulate DNA access and transcription. I recently demonstrated that histone H2A.Z, a variant of histone H2A, is actively exchanged during memory consolidation in both the hippocampus and the cortex, where it acts as a restraint on the formation of recent and remote memory. These findings introduce histone variant exchange as a novel epigenetic regulator of memory formation and transcription in the nervous system. My interests center on elucidating the regulatory role of nucleosome composition and histone variant exchange in cognition, particularly in the context of co-occurring epigenetic modifications. Histone variants are an especially exciting target for memory stabilization because of our recent observation that cortical H2A.Z binding at memory-associated genes is altered long after the cessation of the learning event. Thus, studies aimed at uncovering the mechanisms through which histone exchange is regulated and in turn, how it regulates its downstream targets over time, can provide essential insights into the molecular basis of memory. To this end, my research focuses on multiple stages of memory formation, including initial and transient consolidation events in the hippocampus, as well as the gradual transfer of memories to the cortex in a process termed systems consolidation. An important consideration in studies focused on any single modification is that epigenetic modifications do not occur in isolation and instead work together to regulate gene expression and, ultimately, behaviour. I am especially interested in understanding the coordinated effects of histone variants, post-translational modifications and DNA methylation in regulating memory formation and memory maintenance. These related lines of research converge on the broader issue of stimulus-induced plasticity in neural networks and their implications for establishing persistent behavioural outcomes.

近期论文

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Advanced In vivo Use of CRISPR/Cas9 and Anti-sense DNA Inhibition for Gene Manipulation in the Brain.Walters BJ, Azam AB, Gillon CJ, Josselyn SA, Zovkic IB.Front Genet 2015;6:362 pubmed Memory-Associated Dynamic Regulation of the "Stable" Core of the Chromatin Particle.Zovkic IB, Sweatt JD.Neuron 2015 Jul;87(1):1-4 pubmed Building up and knocking down: An emerging role for epigenetics and proteasomal degradation in systems consolidation.Walters BJ, Zovkic IB.Neuroscience 2015 Aug;300:39-52 pubmed H2A.Z helps genes remember their history so we can remember ours.Zovkic IB, Walters BJ.Bioessays 2015 Apr; pubmed Histone H2A.Z subunit exchange controls consolidation of recent and remote memory.Zovkic IB, Paulukaitis BS, Day JJ, Etikala DM, Sweatt JD.Nature 2014 Nov;515(7528):582-6 pubmed Interindividual Variability in Stress Susceptibility: A Role for Epigenetic Mechanisms in PTSD.Zovkic IB, Meadows JP, Kaas GA, Sweatt JD.Front Psychiatry 2013;4:60 pubmed Epigenetic regulation of memory formation and maintenance.Zovkic IB, Guzman-Karlsson MC, Sweatt JD.Learn. Mem. 2013;20(2):61-74 pubmed Epigenetic mechanisms in learned fear: implications for PTSD.Zovkic IB, Sweatt JD.Neuropsychopharmacology 2013 Jan;38(1):77-93 pubmed Role of medial prefrontal cortex dopamine in age differences in response to amphetamine in rats: locomotor activity after intra-mPFC injections of dopaminergic ligands.Mathews IZ, McCormick CM.Dev Neurobiol 2012 Nov;72(11):1415-21 pubmed Social instability stress in adolescent male rats alters hippocampal neurogenesis and produces deficits in spatial location memory in adulthood.McCormick CM, Thomas CM, Sheridan CS, Nixon F, Flynn JA, Mathews IZ.Hippocampus 2012 Jun;22(6):1300-12 pubmed