Wayne Brake, PhD

Estrogen, learning and memory, female cognition, dopamine

Research Overview: The Brake lab examines how natural fluctuations in ovarian hormones across the estrus cycle in rats affect normal brain function and plasticity. There are two lines of research currently being carried out in the lab:

Natural fluctuations in ovarian hormones such as estrogen were once thought to only play a role in sexual behaviors. Now it is well established that they play a critical role in certain types of cognition as well. One example of this is the cognitive strategy used to solve a maze for a reward. When estrogen levels are lower, females tend to use a "response" strategy whereas when the levels are higher, they tend to use a "place" strategy to find a reward. These two strategies are influenced by two different areas of the brain; the dorsal striatum and the hippocampus, respectively. Research in the lab explores how estrogen affects underlying dopamine transmission to influence cognitive strategy.

Schizophrenia is a complex disease that presents differently in men and women. Women tend to have a relief of symptoms during pregnancy (when hormones are elevated), while others may develop the disease following menopause (when ovarian hormones decrease). Moreover, women respond to antipsychotic medication differently from men. This suggests a role for estrogen and other ovarian hormones in the symptomology and treatment response to schizophrenia. We are examining how estrogen influences dopamine transmission in areas linked to the disease and how antipsychotic drug effects may be influenced by estrogen.

Lab members

Current graduate students

Anne Almey (PhD Candidate)
Dema Hussain (PhD Candidate)
Waqqas Shams (PhD Candidate)
Arne Hantson (MA Student)
Czarina Evangelista (MA Student)

Current Undergraduate Students

Lauren Arenal
Joshua Oliel
Yaman Al-Qadri
Alex Tsanev
Jesse Duchemin
Lukas Henning (Exchange Honours Student from Maastricht University; Netherlands)

Graduate Student Alumni (current position)

Matt Quinlan (Prof: Cal State, San Bernadino)
Dan Madularu (Post Doc: McGill)
Nicole Gervais (Post Doc: U Mass, Amherst)

Hussain D, Shams WM, Brake WG (2014) Estrogen and memory system bias in females across the lifespan. Transl Neurosci 5:35-50. [Content]

Almey A, Cannel E, Bertram K, Filardo E, Milner TA, Brake WG (2014) Medial prefrontal cortical estradiol rapidly alters memory system bias in female rats: Ultrastructural analysis reveals membrane-associated estrogen receptors as potential mediators. Endocrinology [Epub ahead of print] [PubMed] [Content]

Gervais NJ, Jacob S, Brake WG, Mumby DG (2014) Modulatory effect of 17-beta estradiol on performance of ovariectomized rats on the Shock-Probe test. Physiol Behav 131:129-135. [PubMed] [Content]

Madularu D, Shams WM, Brake WG (2014) Estrogen potentiates the behavioral and nucleus accumbens dopamine response to continuous haloperidol treatment in female rats. Eur J Neurosci 39:257-265. [PubMed] [Content]

Almey A, Hafez NM, Hantson A, Brake WG (2013) Deficits in latent inhibition induced by estradiol replacement are ameliorated by haloperidol treatment. Front Behav Neurosci 7:136. [PubMed] [Content]

Quinlan MG, Almey A, Caissie M, LaChappelle I, Radiotis G, Brake WG (2013) Estradiol and striatal dopamine receptor antagonism influence memory system bias in the female rat. Neurobiol Learn Mem 106:221-229. [PubMed] [Content]

Gervais NJ, Jacob S, Brake WG, Mumby DG (2013) Systemic and intra-rhinal-cortical 17-beta estradiol administration modulate object-recognition memory in ovariectomized female rats. Horm Behav 64:642-652. [PubMed] [Content]

Hussain D, Hoehne A, Woodside B, Brake WG (2013) Reproductive experience modifies the effects of estradiol on learning and memory bias in female rats. Hormones and Behavior 63:418-423. [PubMed] [Content]

Almey A, Filardo EJ, Milner TA, Brake WG (2012) Estrogen receptors are found in glia and at extranuclear neuronal sites in the dorsal striatum of female rats: evidence for cholinergic but not dopaminergic colocalization. Endocrinology 153:5373-5378. [PubMed] [Content]

Laplante F, Brake WG, Chehab SL, Sullivan RM (2012) Sex differences in the effects of perinatal anoxia on dopamine function in rats.Neurosci Lett 506:89-93. [PubMed] [Content]

Salmaso N, Quinlan MG, Brake WG, Woodside B (2011) Changes in dendritic spine density on layer 2/3 pyramidal cells within the cingulate cortex of late pregnant and postpartum rats. Horm Behav 60:65-71. [PubMed] [Content]

Quinlan MG, Duncan A, Loiselle C, Graffe N, Brake WG (2010) Latent inhibition is affected by phase of estrous cycle in female rats.Brain Cogn 74:244-248. [PubMed] [Full]

Baharnoori M, Brake WG, Srivastava LK (2009) Prenatal immune challenge induces developmental changes in the morphology of pyramidal neurons of the prefrontal cortex and hippocampus in rats. Schizophr Res 107:99-109. [PubMed] [Full]

Nofrey BS, Ben-Shahar OM, Brake WG (2008) Estrogen abolishes latent inhibition in ovariectomized female rats. Brain Cogn 66:156-160. [PubMed] [Full]

Quinlan MG, Hussain D, Brake WG (2008) Use of cognitive strategies in rats: the role of estradiol and its interaction with dopamine. Horm Behav 53:185-191. [PubMed] [Full]

Gray JD, Punsoni M, Tabori NE, Melton JT, Fanslow V, Ward MJ, Zupan B, Menzer D, Rice J, Drake CT, Romeo RD, Brake WG, Torres-Reveron A, Milner TA (2007) Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress. J Neurosci 27:7196-7207. [PubMed] [Full]

Ben-Shahar O, Keeley P, Cook M, Brake W, Joyce M, Nyffeler M, Heston R, Ettenberg A (2007) Changes in levels of D1, D2, or NMDA receptors during withdrawal from brief or extended daily access to IV cocaine. Brain Res 1131:220-228. [PubMed] [Full]

Priebe K, Romeo RD, Francis DD, Sisti HM, Mueller A, McEwen BS, Brake WG (2005) Maternal influences on adult stress and anxiety-like behavior in C57BL/6J and BALB/cJ mice: a cross-fostering study. Dev Psychobiol 47:398-407. [PubMed] [Full]

Romeo RD, Fossella JA, Bateup HS, Sisti HM, Brake WG, McEwen BS (2004) Maternal separation suppresses TGF alpha mRNA expression in the prefrontal cortex of male and female neonatal C57BL/6 mice. Brain Res Dev Brain Res 152:73-77. [PubMed] [Full]

Brake WG, Zhang TY, Diorio J, Meaney MJ, Gratton A (2004) Influence of early postnatal rearing conditions on mesocorticolimbic dopamine and behavioural responses to psychostimulants and stressors in adult rats. Eur J Neurosci 19:1863-1874. [PubMed] [Full]

Li C, Brake WG, Romeo RD, Dunlop JC, Gordon M, Buzescu R, Magarinos AM, Allen PB, Greengard P, Luine V, McEwen BS (2004) Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice. Proc Natl Acad Sci U S A 101:2185-2190. [PubMed] [Full]

Sullivan RM, Brake WG (2003) What the rodent prefrontal cortex can teach us about attention-deficit/hyperactivity disorder: the critical role of early developmental events on prefrontal function. Behav Brain Res 146:43-55. [PubMed] [Full]

Choi JM, Romeo RD, Brake WG, Bethea CL, Rosenwaks Z, McEwen BS (2003) Estradiol increases pre- and post-synaptic proteins in the CA1 region of the hippocampus in female rhesus macaques (Macaca mulatta). Endocrinology 144:4734-4738. [PubMed] [Full]

Romeo RD, Mueller A, Sisti HM, Ogawa S, McEwen BS, Brake WG (2003) Anxiety and fear behaviors in adult male and female C57BL/6 mice are modulated by maternal separation. Horm Behav 43:561-567. [PubMed] [Full]

Alves SE, Hoskin E, Lee SJ, Brake WG, Ferguson D, Luine V, Allen PB, Greengard P, McEwen BS (2002) Serotonin mediates CA1 spine density but is not crucial for ovarian steroid regulation of synaptic plasticity in the adult rat dorsal hippocampus. Synapse 45:143-151. [PubMed] [Full]

Meaney MJ, Brake W, Gratton A (2002) Environmental regulation of the development of mesolimbic dopamine systems: a neurobiological mechanism for vulnerability to drug abuse? Psychoneuroendocrinology 27:127-138. [PubMed] [Full]

McEwen B, Akama K, Alves S, Brake WG, Bulloch K, Lee S, Li C, Yuen G, Milner TA (2001) Tracking the estrogen receptor in neurons: implications for estrogen-induced synapse formation. Proc Natl Acad Sci U S A 98:7093-7100. [PubMed] [Full]

Brake WG, Alves SE, Dunlop JC, Lee SJ, Bulloch K, Allen PB, Greengard P, McEwen BS (2001) Novel target sites for estrogen action in the dorsal hippocampus: an examination of synaptic proteins. Endocrinology 142:1284-1289. [PubMed] [Full]

Brake WG, Sullivan RM, Gratton A (2000) Perinatal distress leads to lateralized medial prefrontal cortical dopamine hypofunction in adult rats. J Neurosci 20:5538-5543. [PubMed] [Full]

Brake WG, Flores G, Francis D, Meaney MJ, Srivastava LK, Gratton A (2000) Enhanced nucleus accumbens dopamine and plasma corticosterone stress responses in adult rats with neonatal excitotoxic lesions to the medial prefrontal cortex. Neuroscience 96:687-695. [PubMed] [Full]

Brake WG, Sullivan RM, Flores G, Srivastava LK, Gratton A (1999) Neonatal ventral hippocampal lesions attenuate the nucleus accumbens dopamine response to stress: an electrochemical study in the adult rat. Brain Res 831:25-32. [PubMed] [Full]

Brake WG, Boksa P, Gratton A (1997) Effects of perinatal anoxia on the acute locomotor response to repeated amphetamine administration in adult rats. Psychopharmacology (Berl) 133:389-395. [PubMed] [Full]

Brake WG, Sharma S (1997) Anoxia at birth induces behaviorally relevant changes alpha2-noradrenergic receptor binding in the adult rat. McGill Journal of Medicine 3:4-11. [Full]

Brake WG, Noel MB, Boksa P, Gratton A (1997) Influence of perinatal factors on the nucleus accumbens dopamine response to repeated stress during adulthood: an electrochemical study in the rat. Neuroscience 77:1067-1076. [PubMed] [Full]

Brake WG, Pappas BA (1994) Hemicholinium-3 (HC3) blocks the effects of ethylcholine mustard aziridinium (AF64A) in the developing rat. Brain Res Dev Brain Res 83:289-293. [PubMed] [Full]

Dr. Brake earned his BSc. in Psychology at Dalhousie University in Halifax, N.S. and then completed his MSc. at Carleton University in Ottawa. Dr. Brake continued on to complete his Ph.D. in Neurological Sciences at McGill University in 1999. He then continued with his post-doctoral research in Neuroendocrinology at the Rockefeller University in New York City. Prior to coming to Concordia in 2005, Dr. Brake was an Assistant Professor at University of California, Santa Barbara.

Fun fact

I’m funny, you just have to ask!