个人简介

Ph.D. University of Calgary 2001 M.Sc. University of Toronto 1997 B.Sc. University of Toronto 1995

研究领域

Animal Biology Cell Biology Neurobiology Physiology

The Woodin Lab is focused on discovering the cellular mechanisms underlying inhibitory GABAergic synaptic plasticity in the hippocampus. At the centre of our investigation is the K+-Cl cotransporter KCC2, which is essential for maintaining the Cl- gradient necessary for GABAergic transmission. When there is a decrease in KCC2 expression, or when KCC2’s ability to efficiently extrude Cl- decreases, neuronal Cl- regulation is critically disrupted. Failure of neurons to regulate the Cl- gradient results in reduced synaptic inhibition. We discovered that neuronal activity can induce a KCC2-mediated decrease in neuronal Cl–regulation and as a result significantly weaken synaptic inhibition. There are two classes of neurological disorders associated with disrupted neuronal Cl- regulation, and the resulting inhibitory synaptic plasticity: (i) those resulting directly from decreased KCC2 expression and efficacy, such as epileptic seizures; (ii) and those where decreases in KCC2 expression and efficacy occur secondarily due to brain trauma, peripheral nerve injury, or stroke. There are currently no clinical treatments targeted to preventing decreases in KCC2, or towards restoring KCC2 function. Our primary goal is to determine the cellular mechanisms that regulate KCC2 function. Knowledge of these mechanisms is fundamental for the future development of prevention strategies aimed direction at KCC2. We have recently identified two novel KCC2-interacting proteins, Neto2 and the ionotropic glutamate receptor subunit GluK2. These interactions are essential for the oligomerization and efficient function of the transporter. We are currently exploring the functional significance of this KCC2-Neto2-GluK2 interactions at the neuronal and circuit-levels.

近期论文

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Neuronal chloride and excitability — the big impact of small changes.Raimondo, Joseph V, Blake A Richards, and Melanie A Woodin. 2017. Current Opinion in Neurobiology. Elsevier BV, April. doi Top-down modulation of olfactory-guided behaviours by the anterior olfactory nucleus pars medialis and ventral hippocampus. Aqrabawi, Afif J., Caleb J. Browne, Zahra Dargaei, Danielle Garand, C. Sahara Khademullah, Melanie A. Woodin, and Jun Chul Kim. 2016. Nature Communications. Springer Nature, December 22. doi Misregulation of an Activity-Dependent Splicing Network as a Common Mechanism Underlying Autism Spectrum Disorders.Quesnel-Vallières, Mathieu, Zahra Dargaei, Manuel Irimia, Thomas Gonatopoulos-Pournatzis, Joanna Y. Ip, Mingkun Wu, Timothy Sterne-Weiler, et al. 2016. Molecular Cell. Elsevier BV, December. doi Regulation of neuronal chloride homeostasis by neuromodulators. Mahadevan, Vivek, and Melanie A Woodin. The Journal of physiology, no. 10 (March 31) 2016. doi:10.1113/JP271593. pubmed Neto2-null mice have impaired GABAergic inhibition and are susceptible to seizures. Mahadevan, Vivek, Zahra Dargaei, Evgueni A Ivakine, Anna-Maria Hartmann, David Ng, Jonah Chevrier, Jake Ormond, Hans Gerd Nothwang, Roderick R McInnes, and Melanie A Woodin. Frontiers in cellular neuroscience (September 23). doi:10.3389/fncel.2015.00368. pubmed Single cell-derived clonal analysis of human glioblastoma links functional and genomic heterogeneity.Meyer M, Reimand J, Lan X, Head R, Zhu X, Kushida M, Bayani J, Pressey JC, Lionel AC, Clarke ID, Cusimano M, Squire JA, Scherer SW, Bernstein M, Woodin MA, Bader GD, Dirks PB.Proc. Natl. Acad. Sci. U.S.A. 2015 Jan;112(3):851-6 pubmed Parvalbumin and GAD65 interneuron inhibition in the ventral hippocampus induces distinct behavioral deficits relevant to schizophrenia.Nguyen R, Morrissey MD, Mahadevan V, Cajanding JD, Woodin MA, Yeomans JS, Takehara-Nishiuchi K, Kim JC.J. Neurosci. 2014 Nov;34(45):14948-60 pubmed Neurons Are Recruited to a Memory Trace Based on Relative Neuronal Excitability Immediately before Training.Yiu AP, Mercaldo V, Yan C, Richards B, Rashid AJ, Hsiang HL, Pressey J, Mahadevan V, Tran MM, Kushner SA, Woodin MA, Frankland PW, Josselyn SA.Neuron 2014 Aug;83(3):722-35 pubmed Kainate receptors coexist in a functional complex with KCC2 and regulate chloride homeostasis in hippocampal neurons.Mahadevan V, Pressey JC, Acton BA, Uvarov P, Huang MY, Chevrier J, Puchalski A, Li CM, Ivakine EA, Airaksinen MS, Delpire E, McInnes RR, Woodin MA.Cell Rep 2014 Jun;7(6):1762-70 pubmed Patterns across multiple memories are identified over time.Richards BA, Xia F, Santoro A, Husse J, Woodin MA, Josselyn SA, Frankland PW.Nat. Neurosci. 2014 Jul;17(7):981-6 pubmed