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John McLean


PhD Dalhousie

Professor of Neuroscience and Anatomy

Division of BioMedical Sciences
Memorial University of Newfoundland
St. John's, NL, Canada
A1B 3V6

t: 709-864-6039
f:
lab: lab; 709-864-6038

mclean@mun.ca


A Window on Promoting Memory

This research is in collaboration with Dr. Carolyn Harley, Professor emeritus, Dept. of Psychology.  We are investigating the behavioural, physiological, cellular and intracellular substrates involved in learning.  We use a mammalian model- conditioned olfactory learning (Pavlovian-like classical conditioning) in neonate rat pups.  Much has been determined from invertebrate studies concerning learning and memory and, indeed, many signalling events during learning seem to be also present in mammals.  However, knowledge of signalling in mammalian brains related to learning is circumstantial in many cases.  The olfactory system offers a relatively simple mammalian system where behaviour can be directly linked to intracellular signalling.  One such intracellular transcription factor is CREB (cAMP response element binding protein).  We have found that CREB phosphorylation in the olfactory bulb is causal to early olfactory learning.  The noradrenergic receptor agonist, isoproterenol (known to induce learning when paired with an odor) has an important role in CREB activation in the bulb.  We are now examining the intracellular triggers that help to form the memory and even extend memory capabilities.

The funding for this research is from the Canadian Institutes of Health Research (CIHR).

 

Members of the lab include left to right:  John McLean, Andrea Darby-King (research assistant), Matt Grimes (graduate Student), Melissa Christie-fougere (graduate student), Nicolle Stockely (MUCEP student), Wen Cui (graduate student).
 
Figure 1. 5-HT2A receptors and b1-adrenoceptors are co-localized in mitral cells of the olfactory bulb using immunofluorescence and confocal microscopy.  We hypothesize that serotonin and norepinephrine interact on mitral cells and induce intracellular signalling cascades leading to learning.  We can manipulate components of the signalling pathways to promote prolonged olfactory memory. Figure 2.  Western blot analysis of phorphorylated cAMP response element binding protein (pCREB) in the olfactory bulb of pups subjected to odor preference learning (odor + tactile stroke stimulation [O/S]) compared to non learning (odor only, O/O) conditions.  The expression of pCREB is greater in learning pups compared to non-learning pups and is greatest about 10-30 min after training.

 


Awards: Faculty of Medicine Outstanding Teacher Award, 1992 (Med II class) and 2012 (Med 1 class); CIHR Synapse Award 2007: for excellence in developing Canada's new generation of health researchers.

Teaching: Gross Anatomy, Neuroscience to medical and graduate students. 
 
Activities: Coordinator of the Brain Storm Contest for NL high school students (2000-2010).
 
Other Activities: Cross country skiing, running, cycling and softball.

Selected Recent Papers
 

Grimes MT, Powell M, Gutierrez SM, Darby-King A, Harley CW, McLean JH (2015) Epac activation initiates associative odor preference memories in the rat pup. Learn Mem 22:74-82.

Yuan Q, Harley CW, McLean JH (2013) Converging methodologies in a mammalian 'simple system' focused on the biology of memory: Conditioned odor preference in the neonate rat. New York: Springer-Verlag.

Grimes MT, Harley CW, Darby-King A, McLean JH (2012) PKA increases in the olfactory bulb act as unconditioned stimuli and provide evidence for parallel memory systems: Pairing odor with increased PKA creates intermediate- and long-term, but not short-term, memories. Learn Mem 19:107-115.

Grimes MT, Smith M, Li X, Darby-King A, Harley CW, McLean JH (2011) Mammalian intermediate-term memory: New findings in neonate rat. Neurobiol Learn Mem 95:385-3.

Cui W, Darby-King A, Grimes MT, Howland JG, Wang YT, McLean JH, Harley CW (2011) Odor preference learning and memory modify GluA1 phosphorylation and GluA1 distribution in the neonate rat olfactory bulb: Testing the AMPA receptor hypothesis in an appetitive learning model. Learn Mem 18:283-291.

Raineki C, Pickenhagen A, Roth TL, Babstock DM, McLean JH, Harley CW, Lucion AB, Sullivan RM (2010) The neurobiology of infant maternal odor learning. Braz J Med Biol Res 43:914-919.

Christie-Fougere MM, Darby-King A, Harley CW, McLean JH (2009) Calcineurin inhibition eliminates the normal inverted U curve, enhances acquisition and prolongs memory in a mammalian 3'-5'-cyclic AMP-dependent learning paradigm. Neuroscience 158:1277-1283.

McLean JH, Smith A, Rogers S, Clarke K, Darby-King A, Harley CW (2009) A phosphodiesterase inhibitor, cilomilast, enhances cAMP activity to restore conditioned odor preference memory after serotonergic depletion in the neonate rat. Neurobiol Learn Mem 92:63-69

Cui W., Smith A., Darby-King A., Harley, C.W., McLean J.H. (2007)  A temporal-specific and transient cAMP increase characterizes  odorant classical conditioning.  Learning & Memory 14 (3): 126-133

Harley, C.W.,  Darby-King, A., McLean, J.H. (2006) b1-adrenoceptor or a1-adrenoceptor activation initiates early odor preference learning in rat pups: Support for the mitral/cAMP model of odor preference learning.  Learning & Memory 13:8-13.

McLean, J.H., Darby-King, A., Harley, C.W. (2005) Potentiation and prolongation of long-term odor memory in neonate rats using a phosphodiesterase inhibitor.  Neuroscience 135: 329-334.

McLean ,J.H., Harley, C.W. (2004) Olfactory learning in the rat pup: A model that may permit visualization of a mammalian memory trace. NeuroReport 15: 1691-1697 (invited review paper).

Yuan, Q., Harley, C.W., Darby-King, A., Neve, R.L., McLean, J.H. (2003a) Early odor preference learning in the rat: bidirectional effects of cAMP response element-binding protein (CREB) and mutant CREB support a causal role for phosphorylated CREB. Journal of Neuroscience 23: 4760-5.

Yuan, Q., Harley, C.W., McLean, J.H. (2003b) Mitral cell beta1 and 5-HT2A receptor colocalization and cAMP coregulation: a new model of norepinephrine-induced learning in the olfactory bulb. Learning & Memory 10: 5-15.

McLean, J.H., Darby-King, A., Bonnell, W.S. (2001) Neonatal olfactory sensory deprivation decreases BDNF in the olfactory bulb of the rat. Dev Brain Res 128: 17-24.

McLean, J.H., Harley, C.W.,  Darby-King, A., and Yuan, Q.  (1999) pCREB in the neonate rat olfactory bulb is selectively and transiently increased by odor preference-conditioned training. Learning & Memory 6:608-618.

Fawcett, J.P., Aloyz, R., McLean, J.H., Pareek, S., Miller, F.D., McPherson,  P.S., and Murphy, R.A.  (1997) Detection of brain-derived neurotrophic factor in a vesicular fraction of brain synaptosomes. J.Biol.Chem. 272:8837-8840.


 
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