POSTERS Au s t r A l i A n neuroscience so c i e t y An n u A l Me e t i n g • go l d co A s t • 29 JA n u A r y - 1 Fe b r u A r y 2012 Page 69 Page 70 Au s t r A l i A n neuroscience so c i e t y An n u A l Me e t i n g • go l d co A s t • 29 JA n u A r y - 1 Fe b r u A r y 2012 POSTERS Monday POS-MON-001 POS-MON-002 IMPORTANT ROLE FOR TEN-M2 IN THE FORMATION EPIGENETIC REGULATION OF MEF2C AND HDAC- OF FUNCTIONAL BINOCULAR CIRCUITS IN THE 5 IN MOUSE VISUAL CORTEX BY ENRICHED MOUSE VISUAL SYSTEM ENVIRONMENT 1 1 2 1 Young T.R.1, Bourke M. , Sawatari A. , Fassler R. and Leamey C.A. 1, Elanggovan B.1, Ching T.1 and Sng J.1, 2 1 Oikawa H. Discipline of Physiology, School of Medical Sciences and Bosch 1Singapore Institute for Clinical Sciences, A*Star. 2Department of 2 Institute, University of Sydney, Australia. Department of Molecular Physiology, Yong Loo Lin School of Medicine, National University of Medicine, Max-Planck Institute for Biochemistry, Martinsried, Singapore. Germany. Purpose: Recent studies have shown that the persistence of enriched Increasing evidence suggests that multiple Teneurin (Ten-m) molecules environment (EE) induces synaptic plasticity in the neuronal circuitry have important, complementary roles in the organisation of binocular during brain development. In this study we investigated the interplay circuits. Previous experiments have indicated a specific role for Ten-m2 between EE and epigenetics that organize experience-induced plasticity in regulating the size and location of ipsilateral retinal projections, with in the visual cortex (VC). Methods: C57BL/6J mice were randomly Ten-m2 KO mice having fewer ipsilateral projections arising from ventral assigned to standard conditions (SC) or EE conditions 2-3 days before retina projecting to their topographically-corresponding target region birth. Under SC, mice were singly-housed in a basic cage without any (rostral) within the dorsal lateral geniculate nucleus (dLGN). Here, we enriched objects until postnatal 56 (P56). Whereas, mice assigned to look at the impact that these changes may have on visual function and EE were housed in a Perspex cage containing a variety of objects until behaviour of animals lacking Ten-m2. Immunostaining for the immediate- P56. Golgi-Cox staining was performed on VC of SC (n=3) and EE mice early gene, c-fos, revealed that the area of primary visual cortex (V1) (n=3) to assess dendritic differences. The mice VC of SC (n=3) and EE driven by ipsilateral inputs was significantly reduced (p<0.05, multivariate (n=3) were dissected for RNA extraction which were examined to validate ANOVA) in Ten-m2 KO mice (n=6), compared to WTs (n=4). Visually- expression levels of synaptic plasticity related genes: Mef2C, HDAC- evoked potential (VEP) recordings further showed that the magnitude 5, ApoD, ARC, Egr1, Fos, Per2, TMEM, 176a and TrkA in Real-time of cortical responses in Ten-m2 KOs (n=3) was decreased, compared quantitative PCR (qPCR) and Chromatin Immunoprecipitation (ChIP- to WTs (n=13), most noticeably for ipsilateral VEP responses (p<0.05, qPCR). Results: Golgi-Cox staining revealed enhanced morphological multivariate ANOVA). Ten-m2 KO VEP responses also displayed an dendritic outgrowth in P28 EE mice, which is not observed in P56 EE increased latency and duration (p<0.05, multivariate ANOVA). A visual mice. Mef2C and TrkA were significantly up-regulated in P28 EE, whilst discrimination task was specifically designed to challenge the dorsal HDAC-5 was significantly down-regulated after EE in qPCR analysis. visual field of these animals. Here, Ten-m2 KOs (n=9) showed a specific ChIP-qPCR showed reduced interaction between HDAC-5 and Mef2C impairment in their ability to discriminate between dorsally-located visual promoter and increased level of acetylated histones in EE. Conclusion: stimuli (p<0.005, Mann-Whitney U-test), compared to WTs (n=11). This is These finding indicate that the possibility of the interplay between consistent with both the ventral retinal deficit and data regarding cortical EE and epigenetics in the VC, leading to new therapies targeting at function in these mice. Together, these data highlight the importance that epigenetic factors for recovery of function in developmental and learning Ten-m2 has in regulating the formation of functional binocular circuits in disorders. the mouse visual system. POS-MON-003 POS-MON-004 EFFECTS OF REPETITIVE TRANSCRANIAL MAGNETIC DEVELOPMENTAL VITAMIN D DEFICIENCY IS STIMULATION ON REVERSAL LEARNING AND ASSOCIATED WITH ENHANCED SPONTANEOUS HIPPOCAMPAL DENDRITES IN EPHRIN-A2-/- MICE HYPERLOCOMOTION THAT IS AMELIORATED BY AMPHETAMINE PRE-TREATMENT Makowiecki K.1, 2, Rodger J.1 and Hammond G.1, 2 1School of Animal Biology University of WA. 2School of Psychology Lefevre E.M.1, Eyles D.W.1, 2, 3 and Burne T.H.J.1, 2, 3 University of WA. 1School of Biomedical Science, University of Queensland, St Lucia, QLD 4072 Australia. 2Queensland Brain Institute, University of Repetitive transcranial magnetic stimulation (rTMS) is thought to facilitate Queensland, St Lucia, QLD 4072 Australia. 33Queensland Centre for brain plasticity. However, few studies address anatomical changes Mental Health Research, Wacol, QLD 4076 Australia. following rTMS in relation to behaviour. Purpose This study examined effects of rTMS on hippocampal dendritic spine densities and reversal Purpose:PET studies indicate that schizophrenic patients are more learning in a two-choice visual discrimination task comparing wild-type vulnerable to the effects of amphetamine. Developmental Vitamin D mice and ephrin-A2-/- mice, a model with abnormal neural connectivity (DVD) deficiency is an environmental risk factor for schizophrenia. In and impaired reverse learning strategy (1). Methods Using a Y-maze, rats, DVD-deficiency leads to an increased susceptibility to the dopamine mice were trained to associate food rewards with one visual stimulus. (DA) releasing effects of amphetamine. This vulnerability is thought After learning this association, the rewarded stimulus was switched for to be due to an underlying endogenous dopaminergic sensitization. the previously incorrect stimulus (reversal learning phase). Complex The aim of this study was to examine whether DVD-deficiency in rats waveform, subthreshold rTMS was applied daily to 50% of mice in would lower the threshold of amphetamine-mediated DA sensitization. the reverse phase. Mice were terminally anesthetised after 35 days Methods:DVD-deficient (n=68) and Control (n=72) Sprague Dawley rats in the reversal learning phase and brains stained with Golgi. Results were administered either a Full (n=48), Intermediary (n=46) amphetamine Behavioural results did not support hypothesised reverse learning or Saline (n=46) treatment regime, three times per week for three weeks. deficits observed previously (1) and found no other differences between After a 28d withdrawal period, sensitization was assessed by locomotor genotypes or stimulation conditions. Mice of both genotypes were slow to response to a low dose amphetamine challenge. Prepulse inhibition learn the initial learning task and few mice learned the reversal learning (PPI) to an acoustic startle response, novelty-induced hyperlocomotion task. Analysis of Golgi-stained sections from ephrin-A2-/- mice revealed and DA transporter (DAT) binding in the Nucleus accumbens (Nacc) increased dendrite length and a trend towards spine density increasing were also assessed. Results:At baseline, DVD-deficiency enhanced in CA1, but decreasing in the dentate granular region following rTMS. novelty-induced hyperlocomotion (p < 0.01). Although the current Conclusion rTMS had no effect on learning behaviour in WT or KO mice amphetamine pre-treatment regime did not result in sensitization, it despite inducing anatomical changes in the hippocampus. Comparison did selectively decrease novelty-induced hyperlocomotion in DVD- with previous studies suggests motivation confounded learning results, deficient rats (p < 0.01). PPI and DAT density were unaffected by DVD- as mice were food-deprived to lose 10% of their weight, instead of deficiency or amphetamine pre-treatment. Conclusion:The absence 20% as previously. (1) Arnall, S., Cheam, L.Y., Smart, C., Rengel, A., of sensitization seen in this study may have been due to source of Fitzgerald, M., Thivierge, J.P., Rodger, J. (2010). Behavioural Brain outbred rat strain, time of amphetamine administration, associative Research, 209, 109-113. components or testing paradigm. However, DVD-deficiency enhanced spontaneous hyperlocomotion, which replicates previous findings. The fact that this was selectively decreased by prior amphetamine treatment is consistent with the idea that DVD-deficiency induces an underlying DA abnormality. Au s t r A l i A n neuroscience so c i e t y An n u A l Me e t i n g • go l d co A s t • 29 JA n u A r y - 1 Fe b r u A r y 2012 Page 71 POSTERS Monday POS-MON-005 POS-MON-006 CREATING THE CORTEX: COMPUTATIONAL MYCBP2 CONTROLS GUIDANCE OF ROBO2 MODELLING OF THE PATTERNING OF GENES AXONS DURING DEVELOPMENT OF THE MURINE UNDERLYING CORTICAL AREA DEVELOPMENT OLFACTORY SYSTEM Giacomantonio C.E.1 and Goodhill G.J.1, 2 James G., Conway J., Key B. and Beverdam A. 1Queensland Brain Institute, The University of Queensland. 2School of Brain Growth and Regeneration Lab, School of Biomedical Science, Mathematics and Physics, The University of Queensland. University of Queensland. The cerebral cortex is divided into many functionally specialised areas. Purpose: Robo and Slit molecules are crucial axon guidance factors The development of these areas is dependent on the coordinated during the development and regeneration of the central nervous system. expression of several genes. In the embryonic mouse telecephalon, Fgf8 However, the molecular interactions that these molecules take part in to is expressed at the anterior pole while the transcription factors Emx2, shape the axon tracts in the CNS remain largely unknown.
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