Neurogenic regulation of cognition

About

Professor Perry Bartlett’s laboratory is focussed on understanding the mechanisms that regulate the production and function of new neurons, generated from the resident population of stem/precursor cells in a region of the adult brain known as the hippocampus. This process, called neurogenesis, declines with age, and this loss of new neurons has been associated with impairments in cognitive function as well as mood. The group has discovered that the majority of these stem cells are quiescent, but that they can be activated by stimuli as diverse as physical exercise, antidepressants, and learning.

The Bartlett group is now focussed on identifying the molecular mechanisms that regulate stem cell activation, and on using this knowledge to enhance neurogenesis and ameliorate functional deficits in mouse models of ageing dementia, stroke, anxiety and depression.

In a study that was featured on the front cover of the Journal of Neuroscience (Jhaveri et al.), the Bartlett laboratory reported development of a new cell-sorting method to purify, for the first time, hippocampal stem precursor cells to near homogeneity. The study examined the responsiveness of individual precursors to various stimuli and provided the first evidence for the presence of two distinct subpopulations of quiescent precursors in the hippocampus. The study further showed that these distinct precursors are located in different regions of the hippocampus and generate neuronal progeny that are molecularly different. Since it has been shown that neurons regulating spatial learning and those regulating anxiety and mood are located in different areas of the hippocampus, it suggests that it is the preferential activation of one of the two distinct precursor populations that may underpin the different functions of the hippocampus.

Contact

  +61 7 336 51603

  p.bartlett@uq.edu.au


Group Publications

Research Areas

  • Stem cells in the brain 
  • Neurogenesis 

Group Leader


Research Members

  • Dr Daniel Blackmore

    Research Fellow / AB Manager
    Queensland Brain Institute
  • Dr Lavinia Codd

    Advancement & Scientific Project Officer
    Queensland Brain Institute
    Postdoctoral Research Fellow
    Advancement & Scientific Proj
    Queensland Brain Institute
  • Dr Jing Zhao

    Postdoctoral Research Fellow
    Queensland Brain Institute
  • Dr Mia Schaumberg

    Research Fellow
    School of Human Movement and Nutrition Sciences
    Affiliate Research Fellow
    Queensland Brain Institute
  • Ms Imogen O'Keeffe

    Senior Research Assistant
    Queensland Brain Institute
  • Leanne Cooper

    Ms Leanne Cooper

    Senior Research Assistant
    Queensland Brain Institute
  • Dr Natalie Groves

    Research Assistant
    Queensland Brain Institute
  • Miss Alison Carlisle

    Gen Asst - V. Weisbecker
    School of Biological Sciences
    Research Assistant
    Queensland Brain Institute
  • Emily Frawley

    Miss Emily Frawley

    Research Assistant
    Queensland Brain Institute

Support Staff


Paternal environmental enrichment transgenerationally alters affective behavioral and neuroendocrine phenotypes

Yeshurun, Shlomo, Short, Annabel K., Bredy, Timothy W., Pang, Terence Y. and Hannan, Anthony J. (2017) Paternal environmental enrichment transgenerationally alters affective behavioral and neuroendocrine phenotypes.Psychoneuroendocrinology77 225-235. doi:10.1016/j.psyneuen.2016.11.013

Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain

Ratnu, Vikram S., Emami, Michael R. and Bredy, Timothy W. (2017) Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain. Journal of Neuroscience Research95 1-2: 301-310. doi:10.1002/jnr.23886

Evolving insights into RNA modifications and their functional diversity in the brain

Nainar, Sarah, Marshall, Paul R., Tyler, Christina R., Spitale, Robert C. and Bredy, Timothy W. (2016) Evolving insights into RNA modifications and their functional diversity in the brain. Nature Neuroscience19 10: 1292-1298. doi:10.1038/nn.4378

Increased cocaine-induced conditioned place preference during periadolescence in maternally separated male BALB/c mice: the role of cortical BDNF, microRNA-212, and MeCP2

Viola, Thiago Wendt, Wearick-Silva, Luis Eduardo, De Azeredo, Lucas Araujo, Centeno-Silva, Anderson, Murphy, Conor, Marshall, Paul, Li, Xiang, Singewald, Nicolas, Garcia, Frederico, Bredy, Timothy W. and Grassi-Oliveira, Rodrigo (2016) Increased cocaine-induced conditioned place preference during periadolescence in maternally separated male BALB/c mice: the role of cortical BDNF, microRNA-212, and MeCP2. Psychopharmacology233 17: 3279-3288. doi:10.1007/s00213-016-4373-z

Cognitive neuroepigenetics: the next evolution in our understanding of the molecular mechanisms underlying learning and memory?

Marshall, Paul and Bredy, Timothy W. (2016) Cognitive neuroepigenetics: the next evolution in our understanding of the molecular mechanisms underlying learning and memory?. n p j Science of Learning, 16014. doi:10.1038/npjscilearn.2016.14

Experience-dependent accumulation of N6-methyladenosine in the prefrontal cortex is associated with memory processes in mice

Widagdo, Jocelyn, Zhao, Qiong-Yi, Kempen, Marie-Jeanne, Tan, Men Chee, Ratnu, Vikram S., Wei, Wei, Leighton, Laura, Spadaro, Paola A., Edson, Janette, Anggono, Victor and Bredy, Timothy W. (2016) Experience-dependent accumulation of N6-methyladenosine in the prefrontal cortex is associated with memory processes in mice. Journal of Neuroscience36 25: 6771-6777. doi:10.1523/JNEUROSCI.4053-15.2016

Sex differences in learned fear expression and extinction involve altered gamma oscillations in medial prefrontal cortex

Fenton, Georgina E., Halliday, David M., Mason, Rob, Bredy, Timothy W. and Stevenson, Carl W. (2016) Sex differences in learned fear expression and extinction involve altered gamma oscillations in medial prefrontal cortex.Neurobiology of Learning and Memory135 66-72. doi:10.1016/j.nlm.2016.06.019

The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action

Alaghband, Yasaman, Bredy, Timothy W. and Wood, Marcelo A. (2016) The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action. Neuroscience Letters625 40-46. doi:10.1016/j.neulet.2016.01.023

Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring

Short, A. K., Fennell, K. A., Perreau, V. M., Fox, A., O'Bryan, M. K., Kim, J. H., Bredy, T. W., Pang, T. Y. and Hannan, A. J. (2016) Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring. Translational Psychiatry6 . doi:10.1038/tp.2016.109

Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice

Bjorge, Monica D., Hildrestrand, Gunn A., Scheffler, Katja, Suganthan, Rajikala, Rolseth, Veslemoy, Kusnierczyk, Anna, Rowe, Alexander D., Vagbo, Cathrine B., Vetlesen, Susanne, Eide, Lars, Slupphaug, Geir, Nakabeppu, Yusaku, Bredy, Timothy W., Klungland, Arne and Bjoras, Magnar (2015) Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice. Cell Reports13 12: 2671-2678. doi:10.1016/j.celrep.2015.12.001

Persistent variations in neuronal DNA methylation following cocaine self-administration and protracted abstinence in mice

Baker-Andresen, Danay, Zhao, Qiongyi, Li, Xiang, Jupp, Bianca, Chesworth, Rose, Lawrence, Andrew J. and Bredy, Timothy (2015) Persistent variations in neuronal DNA methylation following cocaine self-administration and protracted abstinence in mice. Neuroepigenetics4 1-11. doi:10.1016/j.nepig.2015.10.001

Long noncoding RNA-directed epigenetic regulation of gene expression is associated with anxiety-like behavior in mice

Spadaro, Paola A., Flavell, Charlotte R., Widagdo, Jocelyn, Ratnu, Vikram S., Troup, Michael, Ragan, Chikako, Mattick, John S. and Bredy, Timothy W. (2015) Long noncoding RNA-directed epigenetic regulation of gene expression is associated with anxiety-like behavior in mice. Biological Psychiatry78 12: 848-859. doi:10.1016/j.biopsych.2015.02.004

Activation-induced cytidine deaminase regulates activity-dependent BDNF expression in post-mitotic cortical neurons

Ratnu, Vikram S., Wei, Wei and Bredy, Timothy W. (2014) Activation-induced cytidine deaminase regulates activity-dependent BDNF expression in post-mitotic cortical neurons. European Journal of Neuroscience40 7: 3032-3039. doi:10.1111/ejn.12678

Methyl CpG Binding Domain Ultra-Sequencing: a novel method for identifying inter-individual and cell-type-specific variation in DNA methylation

Li, X., Baker-Andresen, D., Zhao, Q., Marshall, V. and Bredy, T. W. (2014) Methyl CpG Binding Domain Ultra-Sequencing: a novel method for identifying inter-individual and cell-type-specific variation in DNA methylation.Genes, Brain and Behavior13 7: 721-731. doi:10.1111/gbb.12150

Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation

Li, Xiang, Wei, Wei, Zhao, Qiong-Yi, Widagdo, Jocelyn, Baker-Andresen, Danay, Flavell, Charlotte R., D'Alessio, Ana, Zhang, Yi and Bredy, Timothy W. (2014) Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation. Proceedings of the National Academy of Sciences111 19: 7120-7125. doi:10.1073/pnas.1318906111

Persistent prelimbic cortex activity contributes to enhanced learned fear expression in females

Fenton, Georgina E., Pollard, Amelia K, Halliday, David M., Mason, Rob, Bredy, Timothy W. and Stevenson, Carl W. (2014) Persistent prelimbic cortex activity contributes to enhanced learned fear expression in females. Learning and Memory21 2: 55-60. doi:10.1101/lm.033514.113

Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction

Flavell, Charlotte R., Lambert, Elliot A., Winters, Boyer D. and Bredy, Timothy W. (2013) Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction. Frontiers in Behavioral Neuroscience,7 DEC: 214.1-214.11. doi:10.3389/fnbeh.2013.00214

Exposure to histone deacetylase inhibitors during Pavlovian conditioning enhances subsequent cue-induced reinstatement of operant behavior

Ploense, Kyle L., Kerstetter, Kerry A., Wade, Matthew A., Woodward, Nicholas C., Maliniak, Dan, Reyes, Michael, Uchizono, Russell S., Bredy, Timothy W. and Kippin, Tod E. (2013) Exposure to histone deacetylase inhibitors during Pavlovian conditioning enhances subsequent cue-induced reinstatement of operant behavior. Behavioural Pharmacology24 3: 164-171. doi:10.1097/FBP.0b013e32836104ea

Activation of BDNF signaling prevents the return of fear in female mice

Baker-Andresen, Danay, Flavell, Charlotte R., Li, Xiang and Bredy, Timothy W. (2013) Activation of BDNF signaling prevents the return of fear in female mice. Learning & Memory20 5: 237-240. doi:10.1101/lm.029520.112

The amygdala and medial prefrontal cortex: partners in the fear circuit

Marek, Roger, Strobel, Cornelia, Bredy, Timothy W. and Sah, Pankaj (2013) The amygdala and medial prefrontal cortex: partners in the fear circuit. Journal of Physiology591 10: 2381-2391. doi:10.1113/jphysiol.2012.248575

Dynamic DNA methylation: a prime candidate for genomic metaplasticity and behavioral adaptation

Baker-Andresen, Danay, Ratnu, Vikram and Bredy, Timothy (2013) Dynamic DNA methylation: a prime candidate for genomic metaplasticity and behavioral adaptation. Trends In Neurosciences36 1: 3-13. doi:10.1016/j.tins.2012.09.003

On the potential role of active DNA demethylation in establishing epigenetic states associated with neural plasticity and memory

Li, Xiang, Wei, Wei, Ratnu, Vikram and Bredy, Timothy (2013) On the potential role of active DNA demethylation in establishing epigenetic states associated with neural plasticity and memory. Neurobiology of Learning and Memory,105 125-132. doi:10.1016/j.nlm.2013.06.009

The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing

Barry, Guy, Briggs, J. A., Vanichkina, D. P., Poth, E. M., Beveridge, N. J., Vikram Ratnu, Nayler, S. P., Nones, K., Hu, J., Timothy Bredy, Nakagawa, S., Rigo, F., Taft, R. J., Cairns, M. J., Blackshaw, S., Wolvetang, E. J. and Mattick, J. S. (2013) The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Molecular Psychiatry19 4: 486-494. doi:10.1038/mp.2013.45

p300/CBP-associated factor selectively regulates the extinction of conditioned fear

Wei, Wei, Coelho, Carlos M., Li, Xiang, Marek, Roger, Yan, Shanzhi, Anderson, Shawn, Meyers, David, Mukherjee, Chandrani, Sbardella, Gianluca, Castellano, Sabrina, Milite, Ciro, Rotili, Dante, Mai, Antonello, Cole, Philip A., Sah, Pankaj, Kobor, Michael S. and Bredy, Timothy W. (2012) p300/CBP-associated factor selectively regulates the extinction of conditioned fear. Journal of Neuroscience32 35: 11930-11941. doi:10.1523/JNEUROSCI.0178-12.2012

Emerging role of non-coding RNA in neural plasticity, cognitive function, and neuropsychiatric disorders

Spadaro, Paola A. and Bredy, Timothy W. (2012) Emerging role of non-coding RNA in neural plasticity, cognitive function, and neuropsychiatric disorders. Frontiers in Genetics3 JUL: 132.1-132.16. doi:10.3389/fgene.2012.00132

The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory

Lin, Quan, Wei, Wei, Coelho, Carlos M., Li, Xiang, Baker-Andresen, Dannay, Dudley, Kevin, Ratnu, Vikram S., Boskovic, Zoran, Kobor, Michael S., Sun, Yi E. and Bredy, Timothy W. (2011) The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory. Nature Neuroscience14 9: 1115-1117. doi:10.1038/nn.2891

MicroRNA regulation of neural plasticity and memory

Bredy, Timothy W., Lin, Quan, Wei, Wei, Baker-Andresen, Danay and Mattick, John S. (2011) MicroRNA regulation of neural plasticity and memory. Neurobiology of Learning and Memory96 1: 89-94. doi:10.1016/j.nlm.2011.04.004

Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders

Dudley, Kevin J., Li, Xiang, Kobor, Michael S., Kippin, Tod E. and Bredy, Timothy W. (2011) Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders. Neuroscience and Biobehavioral Reviews35 7: 1544-1551. doi:10.1016/j.neubiorev.2010.12.016

Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300

Marek, Roger, Coelho, Carlos M., Sullivan, Robert K. P., Baker-Andresen, Danay, Li, Xiang, Ratnu, Vikram, Dudley, Kevin J., Meyers, David, Mukherjee, Chandrani, Cole, Philip A., Sah, Pankaj and Bredy, Timothy W. (2011) Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300. Journal of Neuroscience31 20: 7486-7491. doi:10.1523/JNEUROSCI.0133-11.2011

How the epigenome contributes to the development of psychiatric disorders

Bredy, Timothy W., Sun, Yi E. and Kobor, Michael S. (2010) How the epigenome contributes to the development of psychiatric disorders. Developmental Psychobiology52 4: 331-342. doi:10.1002/dev.20424

Paternal deprivation during infancy results in dendrite- and time-specific changes of dendritic development and spine formation in the orbitofrontal cortex of the biparental rodent Octodon degus

Helmekea, C., Seidel, K., Poeggel, G., Bredy, Timothy, Abraham, A. and Braun, K. (2009) Paternal deprivation during infancy results in dendrite- and time-specific changes of dendritic development and spine formation in the orbitofrontal cortex of the biparental rodent Octodon degus. Neuroscience163 3: 790-798. doi:10.1016/j.neuroscience.2009.07.008

Social modulation of associative fear learning by pheromone communication

Bredy, Timothy W. and Barad, Mark (2009) Social modulation of associative fear learning by pheromone communication. Learning and Memory16 1: 12-18. doi:10.1101/lm.1226009

The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear

Timothy, Bredy and Barad, Mark (2008) The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear. Learning & Memory15 1: 39-45. doi:10.1101/lm.801108

Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear

Bredy, Timothy, Wu, Hao, Crego, Cortney, Zellhoefer, Jessica, Sun, Yi E. and Barad, Mark (2007) Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear. Learning & Memory14 4: 268-276. doi:10.1101/lm.500907

Effect of resource availability on biparental care, and offspring neural and behavioral development in the California mouse (Peromyscus californicus)

Bredy, Timothy W., Brown, Richard E. and Meaney, Michael J. (2007) Effect of resource availability on biparental care, and offspring neural and behavioral development in the California mouse (Peromyscus californicus). European Journal of Neuroscience25 2: 567-575. doi:10.1111/j.1460-9568.2006.05266.x

Behavioural epigenetics and psychiatric disorders

Bredy, Timothy (2006) Behavioural epigenetics and psychiatric disorders. Medical Hypotheses68 2: 453-453. doi:10.1016/j.mehy.2006.07.009

Maternal programming of defensive responses through sustained effects on gene expression

Zhang, Tie-Yuan, Bagot, Rose, Parenta, Carine, Nesbitt, Cathy, Bredy, Timothy W., Caldji, Christian, Fish, Eric, Anisman, Hymie, Szyf, Moshe and Meaney, Michael J. (2006) Maternal programming of defensive responses through sustained effects on gene expression. Biological Psychology73 1: 72-89. doi:10.1016/j.biopsycho.2006.01.009

 

  • Professor Rongqiao He, QBI-IBP Joint Laboratory of Neuroscience and Cognition, with the Institute of Biophysics, Beijing, China.
  • Professor Huji Xu, Joint Sino-Australian Neurogenetics Laboratory with the Second Military Medical University (SMMU), Shanghai, China.
  • Matt Brown, The University of Queensland
  • Peter Visscher, The University of Queensland
  • Bryan Mowry, QBI, The University of Queensland
  • David Reutens, The University of Queensland
  • Dr Vidita Vaidya, Tata Institute of Fundamental Research, Mumbai, India
  • Professor Dongyuan Zhao, Fudan University, Shanghai, China
  • Max Lu, University of Surrey, England
  • Gordon Xu, The University of Queensland
  • Helen Cooper, QBI, The University of Queensland
  • Professors Trevor Kilpatrick and Seong-Seng Tan, University of Melbourne.
  • Pankaj Sah, QBI, The University of Queensland
  • Professor Andrew Boyd, Queensland Institute of Medical Research. 

 

Optimising exercise for cognitive function in older adults

It is well known that exercise has a positive influence on cognitive function during aging. However, the optimal dose, intensity and duration of exercise for improving cognitive function is not known, nor are the mechanisms by which exercise may prevent or even reverse cognitive decline.

Join our study to help identify the ‘sweet spot’ for exercise and memory. How much is enough? How much is too little?

Are you aged 65 – 85 and do you want to:

  • become more physically active?
  • participate in regular supervised exercise?
  • learn more about you brain health, learning and memory?
  • be part of supportive community?

Healthy men and women aged 65–85 are invited to participate in a six-month supervised exercise program. To be eligible participants must have no history of stroke or brain trauma, no diagnosed mental illness or cognitive function impairment, be free of significant cardiovascular disease, have a healthy BMI (< 30 kg/m2) and be able and willing to commit to the duration of the exercise program. Participation will include fitness tests, cognitive function testing, MRI scans of the brain, and small blood samples. 

Participants will be divided into three groups to complete either low-intensity (very easy), moderate-intensity (easy) exercise or aerobic-interval (hard) exercise three times per week for six months. All exercise will be supervised and monitored and we will measure cognitive function, fitness, blood hormones, genetic factors and brain volume before beginning exercise, at regular interval during the exercise program and six months following the conclusion of the exercise program. 

Contact

Contact Dr Mia Schaumberg and the Healthy Brain-Ageing Team (healthybrains@uq.edu.au) for further details.

Expression of Interest form

The Healthy Brain-Ageing Team
The Stafford Fox Exercise and Healthy Brain-Ageing Centre
School of Human Movement and Nutrition Sciences (Building 26B)
The University of Queensland | St Lucia, QLD, 4072 | Australia  
+61 7 3346 8770
healthybrains@uq.edu.au
 

Contact

Dr Mia Schaumberg

   +61 7 3346 8770

  healthybrains@uq.edu.au

 

Expression of Interest form

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