Neuronal plasticity, the extraordinary ability of neurons and neural circuits to change with experience, is a fundamental brain principle which provides framework to understand processes such as learning and memory. While these changes occur across multiple domains of neuronal structure and properties, a fascinating and perhaps extreme form of neuronal plasticity is addition of new neurons into existing circuitry i.e. neurogenesis.
Our research program seeks to:
- Understand mechanisms that drive the production and integration of new neurons in the adult brain;
- And investigate functions of adult-born neurons in the regulation of emotion and cognitive processes in health and disease.
The Jhaveri group goals are to uncover new mechanisms that are central to neurogenic regulation and learn how new neurons impact neural circuits and behaviour, and translate these principles to better understand and ultimately treat cognitive and mood-related deficits associated with anxiety and depression.
Our studies have revealed that distinct populations of quiescent neural stem/precursor cells that are activated by multiple, discrete neurochemical signals exist in the adult hippocampus. We have also co-led a study in which we demonstrated that the basolateral amygdala (BLA) harbours resident neural precursors which proliferate and generate new, functional neurons that integrate into the local circuitry in the adult brain.
Our current efforts are focused on understanding the molecular and functional potential of these distinct stem/precursor cells, how their activity is modulated by stress, and what role they play in the regulation of mood and cognition. We are also interested in determining whether new neurons confer behavioural resilience and are important during recovery following chronic stress. A key aspect of our research program is to determine whether selective activation of quiescent neural precursor cells could provide a new approach for the treatment of depressive/anxiety disorders and lead to the development of novel, effective and safe antidepressants.
With a joint appointment between Mater Research Institute, UQ and QBI, we are addressing these questions and have developed, as well as utilised, a combination of innovative and multi-modal approaches including sophisticated mouse genetic models, in vivo lineage tracing using viral vectors, flow cytomtery, cell culture, transcriptomics, high-resolution confocal microscopy, cognitive- and mood-related behavioural tests.
Group leader
Dr Dhanisha Jhaveri
Senior Research Fellow, Queensland Brain Institute
(2021–2023) Dementia Australia Research Foundation Project Grants
Unravelling amygdala-hippocampus neural circuitry of anxiety: Role of adult-born neurons
(2019–2022) NHMRC Project Grant
Guntupalli, Sumasri, Park, Pojeong, Han, Dae Hee, Zhang, Lingrui, Yong, Xuan Ling Hilary, Ringuet, Mitchell, Blackmore, Daniel G., Jhaveri, Dhanisha J., Koentgen, Frank, Widagdo, Jocelyn, Kaang, Bong-Kiun and Anggono, Victor (2023). Ubiquitination of the GluA1 subunit of AMPA receptors is required for synaptic plasticity, memory and cognitive flexibility. The Journal of Neuroscience, 43 (30), JN-RM. doi: 10.1523/jneurosci.1542-22.2023
Jones, Katherine L., Zhou, Mei and Jhaveri, Dhanisha J. (2022). Dissecting the role of adult hippocampal neurogenesis towards resilience versus susceptibility to stress-related mood disorders. npj Science of Learning, 7 (1) 16, 16. doi: 10.1038/s41539-022-00133-y
Blackmore, Daniel G., Steyn, Frederik J., Carlisle, Alison, O’Keeffe, Imogen, Vien, King-Year, Zhou, Xiaoqing, Leiter, Odette, Jhaveri, Dhanisha, Vukovic, Jana, Waters, Michael J. and Bartlett, Perry F. (2021). An exercise ‘sweet spot’ reverses cognitive deficits of ageing by growth hormone-induced neurogenesis. iScience, 24 (11) 103275, 1-25. doi: 10.1016/j.isci.2021.103275
Fast-Trk(B)ing the mechanism of antidepressants
Conroy, Jacinta N., Jhaveri, Dhanisha J. and Coulson, Elizabeth J. (2021). Fast-Trk(B)ing the mechanism of antidepressants. Neuron, 109 (10), 1593-1595. doi: 10.1016/j.neuron.2021.04.027
Cholinergic regulation of adult hippocampal neurogenesis and hippocampus-dependent functions
Madrid, Lidia I., Jimenez-Martin, Javier, Coulson, Elizabeth J. and Jhaveri, Dhanisha J. (2021). Cholinergic regulation of adult hippocampal neurogenesis and hippocampus-dependent functions. The International Journal of Biochemistry & Cell Biology, 134 105969, 1-6. doi: 10.1016/j.biocel.2021.105969
Cell-extrinsic requirement for sulfate in regulating hippocampal neurogenesis
Zhang, Zhe, Jhaveri, Dhanisha, Sharmin, Sazia, Harvey, Tracey J., Dawson, Paul A., Piper, Michael and Simmons, David G. (2020). Cell-extrinsic requirement for sulfate in regulating hippocampal neurogenesis. Biology Open, 9 (7) bio053132, 1-7. doi: 10.1242/bio.053132
Cortisol and major depressive disorder-translating findings from humans to animal models and back
Nandam, L. Sanjay, Brazel, Matthew, Zhou, Mei and Jhaveri, Dhanisha J. (2020). Cortisol and major depressive disorder-translating findings from humans to animal models and back. Frontiers in Psychiatry, 10 974, 974. doi: 10.3389/fpsyt.2019.00974
Groves, Natalie, O’Keeffe, Imogen, Lee, Wendy, Toft, Alexandra, Blackmore, Daniel, Bandhavkar, Saurabh, Coulson, Elizabeth J., Bartlett, Perry F. and Jhaveri, Dhanisha J. (2020). Blockade of TrkB but not p75 NTR activates a subpopulation of quiescent neural precursor cells and enhances neurogenesis in the adult mouse hippocampus. Developmental Neurobiology, 79 (9-10) dneu.22729, 868-879. doi: 10.1002/dneu.22729
Zhao, Jing, Taylor, Chanel J, Newcombe, Estella A, Spanevello, Mark D, O’Keeffe, Imogen, Cooper, Leanne T, Jhaveri, Dhanisha J, Boyd, Andrew W and Bartlett, Perry F (2018) EphA4 regulates hippocampal neural precursor proliferation in the adult mouse brain by d-Serine modulation of N-methyl-d-aspartate receptor signaling. Cerebral Cortex, doi:10.1093/cercor/bhy319
Groves, Natalie J., Zhou, Mei, Jhaveri, Dhanisha J., McGrath, John J. and Burne, Thomas H. J. (2017) Adult vitamin D deficiency exacerbates impairments caused by social stress in BALB/c and C57BL/6 mice. Psychoneuroendocrinology, 86 53-63. doi:10.1016/j.psyneuen.2017.09.003
Evidence for newly generated interneurons in the basolateral amygdala of adult mice
Jhaveri, D. J., Tedoldi, A., Hunt, S., Sullivan, R., Watts, N. R., Power, J. M., Bartlett, P. F. and Sah, P. (2017) Evidence for newly generated interneurons in the basolateral amygdala of adult mice. Molecular Psychiatry, 23 3: 521-532. doi:10.1038/mp.2017.134
Harris, Lachlan, Zalucki, Oressia, Oishi, Sabrina, Burne, Thomas H., Jhaveri, Dhanisha J. and Piper, Michael (2017) A morphology independent approach for identifying dividing adult neural stem cells in the mouse hippocampus. Developmental Dynamics, 247 1: 194-200. doi:10.1002/dvdy.24545
Jhaveri, Dhanisha J., O'Keeffe, Imogen, Robinson, Gregory J., Zhao, Qiong-Yi, Zhang, Zong Hong, Nink, Virginia, Narayanan, Ramesh K., Osborne, Geoffrey W., Wray, Naomi R. and Bartlett, Perry F. (2015) Purification of neural precursor cells reveals the presence of distinct, stimulus-specific subpopulations of quiescent precursors in the adult mouse hippocampus. Journal of Neuroscience, 35 21: 8132-8144. doi:10.1523/JNEUROSCI.0504-15.2015
A comparative study of techniques for differential expression analysis on RNA-seq data
Zhang, Zong Hong, Jhaveri, Dhanisha J., Marshall, Vikki M., Bauer, Denis C., Edson, Janette, Narayanan, Ramesh K., Robinson, Gregory J., Lundberg, Andreas E., Bartlett, Perry F., Wray, Naomi R. and Zhao, Qiong-Yi (2014) A comparative study of techniques for differential expression analysis on RNA-seq data. PLoS One, 9 8: 1-11. doi:10.1371/journal.pone.0103207
Jhaveri, Dhanisha J., Nanavaty, Ishira, Prosper, Boris W., Marathe, Swanand, Husain, Basma F. A., Kernie, Steven G., Bartlett, Perry F. and Vaidya, Vidita A. (2014) Opposing effects of α2- and β-adrenergic receptor stimulation on quiescent neural precursor cell activity and adult hippocampal neurogenesis. PLoS One, 9 6: e98736.1-e98736.11. doi:10.1371/journal.pone.0098736
Saharan, Sumiti, Jhaveri, Dhanisha J. and Bartlett, Perry F. (2013) SIRT1 regulates the neurogenic potential of neural precursors in the adult subventricular zone and hippocampus. Journal of Neuroscience Research, 91 5: 642-659. doi:10.1002/jnr.23199
Taylor, Chanel J., Jhaveri, Dhanisha J. and Bartlett, Perry F. (2013) The therapeutic potential of endogenous hippocampal stem cells for the treatment of neurological disorders. Frontiers in Cellular Neuroscience, 7 JANUARY 2013: 5.1-5.7. doi:10.3389/fncel.2013.00005
Jhaveri, Dhanisha J., Taylor, Chanel J. and Bartlett, Perry F. (2012) Activation of different neural precursor populations in the adult hippocampus: Does this lead to new neurons with discrete functions?. Developmental Neurobiology, 72 7: 1044-1058. doi:10.1002/dneu.22027
Oncostatin M regulates neural precursor activity in the adult brain
Beatus, Paul, Jhaveri, Dhanisha J., Walker, Tara L., Lucas, Peter G., Rietze, Rodney L., Cooper, Helen M., Morikawa, Yoshihiro and Bartlett, Perry F. (2011) Oncostatin M regulates neural precursor activity in the adult brain. Developmental Neurobiology, 71 7: 619-633. doi:10.1002/dneu.20871
Activation of neural precursors in the adult neurogenic niches
Vukovic, Jana, Blackmore, Daniel, Jhaveri, Dhanisha and Bartlett, Perry F. (2011) Activation of neural precursors in the adult neurogenic niches. Neurochemistry International, 59 3: 341-346. doi:10.1016/j.neuint.2011.04.003
Norepinephrine directly activates adult hippocampal precursors via beta(3)-adrenergic receptors
Jhaveri, Dhanisha J., Mackay, Eirinn W., Hamlin, Adam S., Marathe, Swananda V., Nandam, L. Sanjay, Vaidya, Vidita A. and Bartlett, Perry F. (2010) Norepinephrine directly activates adult hippocampal precursors via beta(3)-adrenergic receptors. Journal of Neuroscience, 30 7: 2795-2806. doi:10.1523/JNEUROSCI.3780-09.2010
Yanpallewar, Sudhirkumar U., Fernandes, Kimberly, Marathe, Swananda V., Vadodaria, Krishna C., Jhaveri, Dhanisha, Rommelfanger, Karen, Ladiwala, Uma, Jha, Shanker, Muthig, Verena, Hein, Lutz, Bartlett, Perry, Weinshenker, David and Vaidya, Vidita A. (2010) α2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment. Journal of Neuroscience, 30 3: 1096-1109. doi:10.1523/JNEUROSCI.2309-09.2010
5-HT7, neurogenesis and antidepressants: A promising therapeutic axis for treating depression
Nandam, L. Sanjay, Jhaveri, Dhanisha and Bartlett, Perry (2007) 5-HT7, neurogenesis and antidepressants: A promising therapeutic axis for treating depression. Clinical and Experimental Pharmacology and Physiology, 34 5-6: 546-551. doi:10.1111/j.1440-1681.2007.04608.x
Honours project
Title: Investigating molecular and cellular mechanisms that promote resilience to stress-related mental health conditions
Supervisor: Dr Dhanisha Jhaveri.
Description: The discovery of neurogenesis (i.e. the production and integration of new neurons) in the adult mammalian brain has emerged as an unparalleled mechanism to understand how life experiences shape cellular plasticity, and in turn alter behavioural outcomes. A major focus of our lab is to understand how adult-born neurons contribute to the development of, and recovery from, stress-induced affective behaviour. Using pre-clinical models, our lab has uncovered an important role for adult-born neurons in the regulation of anxiety-like behaviour. Recently, advanced transcriptomics approaches have identified new molecular candidates that may play critical role(s) in this mechanism of stress resilience. Our goal now is to interrogate whether and how these candidate genes contribute to stress-induced anxiety-like behaviour.
Contact: Please email dhanisha@uq.edu.au for more information.
Research Areas
- Neural plasticity
- Chronic stress, anxiety and depression
- Neurogenesis in the adult brain
Latest news
-
QBI’s life-changing mental health research
10 October 2024 -
-
Can you grow new brain cells?
17 November 2017
