Iva Zovkic

faculty_img Academic Title: Assistant ProfessorCampus: UTM
CSB Appointment: Cross-Appointed

Primary Undergraduate Department
Psychology

Graduate Programs:
Cell & Systems Biology,

Biology and Behaviour, Psychology

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

 

Mailing Address:
University of Toronto Mississauga
CCT Building, Rm 4071
3359 Mississauga Road
Mississauga, Ontario L5L 1C6

 

Contact Information:
Office phone: 905-828-3961
Office: CC 4071
Email: iva.zovkic@utoronto.ca
URL:   https://www.utm.utoronto.ca/psychology/faculty-staff/zovkic-iva

 

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

 

Research Description:

Epigenetic mechamisms of learning and memory in rodents; role of histone variants in memory formation and maintenance; age-related cognitive decline.

 

Profile:

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.

 

Publications

2015

Top
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
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Memory-Associated Dynamic Regulation of the "Stable" Core of the Chromatin Particle.Zovkic IB, Sweatt JD.Neuron 2015 Jul;87(1):1-4
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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
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H2A.Z helps genes remember their history so we can remember ours.Zovkic IB, Walters BJ.Bioessays 2015 Apr;
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2014

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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
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2013

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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
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Epigenetic regulation of memory formation and maintenance.Zovkic IB, Guzman-Karlsson MC, Sweatt JD.Learn. Mem. 2013;20(2):61-74
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Epigenetic mechanisms in learned fear: implications for PTSD.Zovkic IB, Sweatt JD.Neuropsychopharmacology 2013 Jan;38(1):77-93
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2012

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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
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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
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2011

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Heightened locomotor-activating effects of amphetamine administered into the nucleus accumbens in adolescent rats.Mathews IZ, Brudzynski SM, McCormick CM.Int. J. Dev. Neurosci. 2011 Aug;29(5):501-7
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Low doses of amphetamine lead to immediate and lasting locomotor sensitization in adolescent, not adult, male rats.Mathews IZ, Kelly H, McCormick CM.Pharmacol. Biochem. Behav. 2011 Feb;97(4):640-6
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Enduring deficits in contextual and auditory fear conditioning after adolescent, not adult, social instability stress in male rats.Morrissey MD, Mathews IZ, McCormick CM.Neurobiol Learn Mem 2011 Jan;95(1):46-56
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2010

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Individual differences in activity predict locomotor activity and conditioned place preference to amphetamine in both adolescent and adult rats.Mathews IZ, Morrissey MD, McCormick CM.Pharmacol. Biochem. Behav. 2010 Mar;95(1):63-71
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Adolescent development, hypothalamic-pituitary-adrenal function, and programming of adult learning and memory.McCormick CM, Mathews IZ.Prog. Neuropsychopharmacol. Biol. Psychiatry 2010 Jun;34(5):756-65
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Investigations of HPA function and the enduring consequences of stressors in adolescence in animal models.McCormick CM, Mathews IZ, Thomas C, Waters P.Brain Cogn 2010 Feb;72(1):73-85
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2009

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Changes in hyporesponsiveness to acute amphetamine and age differences in tyrosine hydroxylase immunoreactivity in the brain over adolescence in male and female rats.Mathews IZ, Waters P, McCormick CM.Dev Psychobiol 2009 Jul;51(5):417-28
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2008

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Chronic social stress in adolescence influenced both amphetamine conditioned place preference and locomotor sensitization.Mathews IZ, Mills RG, McCormick CM.Dev Psychobiol 2008 Jul;50(5):451-9
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Increased depressive behaviour in females and heightened corticosterone release in males to swim stress after adolescent social stress in rats.Mathews IZ, Wilton A, Styles A, McCormick CM.Behav. Brain Res. 2008 Jun;190(1):33-40
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Effects of chronic social stress in adolescence on anxiety and neuroendocrine response to mild stress in male and female rats.McCormick CM, Smith C, Mathews IZ.Behav. Brain Res. 2008 Mar;187(2):228-38
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2007

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Female and male rats in late adolescence differ from adults in amphetamine-induced locomotor activity, but not in conditioned place preference for amphetamine.Mathews IZ, McCormick CM.Behav Pharmacol 2007 Nov;18(7):641-50
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HPA function in adolescence: role of sex hormones in its regulation and the enduring consequences of exposure to stressors.McCormick CM, Mathews IZ.Pharmacol. Biochem. Behav. 2007 Feb;86(2):220-33
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