John McLean

Professor of Neuroscience and Anatomy PhD Dalhousie

Neuroscience

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.

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 olfac

Grimes MT, Smith M, Li X, Darby-King A, Harley CW, McLean JH (2011) Mammalian i

Cui W, Darby-King A, Grimes MT, Howland JG, Wang YT, McLean JH, Harley CW (2011

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 inhi.

McLean JH, Smith A, Rogers S, Clarke K, Darby-King A, Harley CW (2009) A phosph

Cui W., Smith A., Darby-King A., Harley, C.W., McLean J.H. (2007) A temporal-sp

Harley, C.W., Darby-King, A., McLean, J.H. (2006) b1-adrenoceptor or a1-adrenoc

McLean, J.H., Darby-King, A., Harley, C.W. (2005) Potentiation and prolongation

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

Yuan, Q., Harley, C.W., McLean, J.H. (2003b) Mitral cell beta1 and 5-HT2A recep

McLean, J.H., Darby-King, A., Bonnell, W.S. (2001) Neonatal olfactory sensory d

McLean, J.H., Harley, C.W., Darby-King, A., and Yuan, Q. (1999) pCREB in the ne

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.