Melanie Woodin

faculty_img Academic Title: Associate Professor

Campus: St. George

CSB Appointment: Full

Primary Undergraduate Department:
Cell & Systems Biology

Graduate Programs:
Cell & Systems Biology

Titles and Honors:

Academic or Administrative Appointments:
Director, Human Biology Program

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

 

Mailing Address
Department of Cell & Systems Biology
University of Toronto
25 Harbord St.
Toronto, ON M5S 3G5
Canada

 

Contact Information
Office phone: 416-978-8646
Office: RW 303B
Lab: RW302/303/323/318
Lab phone: 416-978-1406
Email: m.woodin@utoronto.ca
URL:

 

Research Areas
Animal Biology
Cell Biology
Neurobiology
Physiology

 

Research

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.

 

Publications

2017

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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.
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2016

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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.
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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.
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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.
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2015

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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.
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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
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2014

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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
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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
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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
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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
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2013

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Muscarinic acetylcholine receptor activation prevents disinhibition-mediated LTP in the hippocampus.Takkala P, Woodin MA.Front Cell Neurosci 2013;7:16
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Neto2 is a KCC2 interacting protein required for neuronal Cl- regulation in hippocampal neurons.Ivakine EA, Acton BA, Mahadevan V, Ormond J, Tang M, Pressey JC, Huang MY, Ng D, Delpire E, Salter MW, Woodin MA, McInnes RR.Proc. Natl. Acad. Sci. U.S.A. 2013 Feb;110(9):3561-6
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2012

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Increasing CRTC1 function in the dentate gyrus during memory formation or reactivation increases memory strength without compromising memory quality.Sekeres MJ, Mercaldo V, Richards B, Sargin D, Mahadevan V, Woodin MA, Frankland PW, Josselyn SA.J. Neurosci. 2012 Dec;32(49):17857-68
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Refuting the challenges of the developmental shift of polarity of GABA actions: GABA more exciting than ever!.Ben-Ari Y, Woodin MA, Sernagor E, Cancedda L, Vinay L, Rivera C, Legendre P, Luhmann HJ, Bordey A, Wenner P, Fukuda A, van den Pol AN, Gaiarsa JL, Cherubini E.Front Cell Neurosci 2012;6:35
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Hyperpolarizing GABAergic transmission requires the KCC2 C-terminal ISO domain.Acton BA, Mahadevan V, Mercado A, Uvarov P, Ding Y, Pressey J, Airaksinen MS, Mount DB, Woodin MA.J. Neurosci. 2012 Jun;32(25):8746-51
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2011

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Disinhibition-Mediated LTP in the Hippocampus is Synapse Specific.Ormond J, Woodin MA.Front Cell Neurosci 2011;5:17
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Endogenous GABA(A) and GABA(B) receptor-mediated electrical suppression is critical to neuronal anoxia tolerance.Pamenter ME, Hogg DW, Ormond J, Shin DS, Woodin MA, Buck LT.Proc. Natl. Acad. Sci. U.S.A. 2011 Jul;108(27):11274-9
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2010

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GABAergic synaptic transmission regulates calcium influx during spike-timing dependent plasticity.Balena T, Acton BA, Woodin MA.Front Synaptic Neurosci 2010;2:16
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Spike-timing dependent plasticity in inhibitory circuits.Lamsa KP, Kullmann DM, Woodin MA.Front Synaptic Neurosci 2010;2:8
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2009

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Disinhibition mediates a form of hippocampal long-term potentiation in area CA1.Ormond J, Woodin MA.PLoS ONE 2009;4(9):e7224
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2008

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Coincident pre- and postsynaptic activity downregulates NKCC1 to hyperpolarize E(Cl) during development.Balena T, Woodin MA.Eur. J. Neurosci. 2008 May;27(9):2402-12
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Extracellular potassium regulates the chloride reversal potential in cultured hippocampal neurons.Balena T, Acton BA, Koval D, Woodin MA.Brain Res. 2008 Apr;1205:12-20
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2007

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Role of activity-dependent regulation of neuronal chloride homeostasis in development.Fiumelli H, Woodin MA.Curr. Opin. Neurobiol. 2007 Feb;17(1):81-6
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2006

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Recent advances in basic neurosciences and brain disease: from synapses to behavior.Bi GQ, Bolshakov V, Bu G, Cahill CM, Chen ZF, Collingridge GL, Cooper RL, Coorssen JR, El-Husseini A, Galhardo V, Gan WB, Gu J, Inoue K, Isaac J, Iwata K, Jia Z, Kaang BK, Kawamata M, Kida S, Klann E, Kohno T, Li M, Li XJ, MacDonald JF, Nader K, Nguyen PV, Oh U, Ren K, Roder JC, Salter MW, Song W, Sugita S, Tang SJ, Tao Y, Wang YT, Woo N, Woodin MA, Yan Z, Yoshimura M, Xu M, Xu ZC, Zhang X, Zhen M, Zhuo M.Mol Pain 2006;2:38
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Excitatory actions of GABA mediate severe-hypoxia-induced depression of neuronal activity in the pond snail (Lymnaea stagnalis).Cheung U, Moghaddasi M, Hall HL, Smith JJ, Buck LT, Woodin MA.J. Exp. Biol. 2006 Nov;209(Pt 22):4429-35
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2003

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Coincident pre- and postsynaptic activity modifies GABAergic synapses by postsynaptic changes in Cl- transporter activity.Woodin MA, Ganguly K, Poo MM.Neuron 2003 Aug;39(5):807-20
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2002

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Trophic factor-induced excitatory synaptogenesis involves postsynaptic modulation of nicotinic acetylcholine receptors.Woodin MA, Munno DW, Syed NI.J. Neurosci. 2002 Jan;22(2):505-14
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