SULSA Professor and Sixth Century Chair in Cell Biology
School of Medical Sciences
University of Aberdeen

AB25 2ZD - Aberdeen
Scotland, United Kingdom

+44 1224 555904
+44 1224 555915
t.harkany@abdn.ac.uk

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> Position as Young Investigator at the ENI Aberdeen
Date posted: Tuesday 13 April 2010
Position as Young Investigator at the ENI Aberdeen

Cannabis is the most widely used illicit recreational drug. However, very limited information is available as to the developmental functions of the endocannabinoid system mediating marijuana actions in the brain and the molecular signature of in utero cannabis exposure that underpins altered neuronal development.

A causal relationship between prenatal drug exposure and behavioural deficits that endure into the adulthood of affected offspring formulates the concept of ‘prenatal drug addiction’. Accordingly, even brief episodes of maternal drug abuse can impose significant changes at the transcriptome or proteome levels if drug exposure coincides with fundamental events of neuronal specification.

Our work is centred on the concept that maternal cannabis smoking disrupts the temporal and spatial precision of endocannabinoid signalling in the fetal brain thus impacting the acquiring of neuronal identity, and consequently, the establishment of coherent neuronal network functions.

We have successfully studied – utilizing cell biology, live-cell imaging, systems neuroscience, neuropharmacology and molecular genetics – how endocannabinoid signalling affects the proliferation of neural progenitors, long-range cell migration, and the morphogenesis of cortical neurons. We have recently applied this knowledge to gain insights in how endocannabinoid signalling networks interact with other developmentally-regulated signalling cassettes to control neuronal network formation in the developing cerebrum.

Our work is supported by the Scottish Universities Life Science Alliance, the Medical Research Council (MRC), EU Framework 7 program, the European Molecular Biology Organization, Alzheimer’s Association and NIDA.

Selected publications:

1.   Minkeviciene R, Rheims S, Dobszay MB, Zilberter M, Hartikainen J, Fülöp L, Penke B, Zilberter Y, Harkany T, Pitkänen A, Tanila H. Amyloid β-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci 2009, 29:3453-3462.

2.   Zilberter M, Holmgren C, Shemer I, Silberberg G, Grillner S, Harkany T*, Zilberter Y*. Input specificity and dependence of spike timing-dependent plasticity on preceding postsynaptic activity at unitary connections between neocortical layer 2/3 pyramidal cells. Cereb Cortex 2009, available online: February 4.

3.   Mulder J, Augado T, Keimpema E, Barabas K, Ballaster Rosado CJ, Nguyen L, Monory K, Marsicano G, Di Marzo V, Hurd YL, Guillemot F, Mackie K, Lutz B, Guzman M, Lu H-C, Galve-Roperh I, Harkany T. Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning. Proc Natl Acad Sci USA 2008, 105:8760-8765.

4.   Harkany T, Mackie K, Doherty P. Wiring and firing neuronal networks: endocannabinoids take center stage. Curr Opin Neurobiol 2008, 18:338-345.

5.   Berghuis P, Rajnicek AM, Morozov YM, Ross RA, Mulder J, Monory K, Marsicano G, Matteoli M, Canty A, Yanagawa Y, Rakic P, Lutz B, Mackie K, Harkany T. Hardwiring the brain: endocannabinoids shape neuronal connectivity, Science 2007, 316:1212-1216.

- neuropharmacology,
- developmental neurobiology,
- neuroanatomy,
- behavioral neurosciences,
- cell biology experimentation.