Results transmission / behaviour

The key objective of this Research Team was to study the consequence of interference with potential key molecules and adaptor proteins involved in regulation of synaptic function for cognitive function and autonomic regulation.

Results

This workpackage developed new tools to investigate mouse models of depression
and cognitive decline. We developed and used a spectrum of behavioural, autonomic and
neurochemical measures with translational value. The novel behavioural and neurochemical methodology was investigated in genetic mouse models for improved characterization of models of cognitive and emotional dysfunction. We identified the 5‐HT7 receptor subtype as target to improve cognitive function. The ESRs visited different partner labs and collaborated to achieve the scientific aims as indicated by several joint publications. 2 ESRs from WP5.1 and WP5.2 are expected to successfully defend their PhD in 2014. Experimental results from this scientific work has been published in  peer‐reviewed journals.

  • Agorastos A, Boel JA, Heppner PS, Hager T, Moeller‐Bertram T, Haji U, Motazedi A, Yanogi MA, Baker DG, Stiedl O (2013) Diminished vagal activity and blunted diurnal variation of heart rate dynamics in posttraumatic stress disorder. Stress 16: 300‐310.
  • Eriksson TE, Holst S, Stan TL, Hager T, Sjögren B, Ögren SO, Svenningsson P, Stiedl O (2012) 5‐HT1A and 5‐HT7 receptors interact in the regulation of emotional learning: implications for the mechanisms of selective serotonin reuptake inhibitors. Neuropharmacology 63: 1150‐1160.
  • Hager T, Maroteaux G, du Pont P, Julsing J, van Vliet R, Stiedl O: Munc18‐1 haploinsufficiency results in enhanced anxiety‐like behavior as determined by heart rate responses in mice. Behav Brain Res (in press; available online at doi: 10.1016/j.bbr.2013.11.033) Hager T, Jansen RF, Pieneman AW, Manivannan SN, Golani I, Smit AB, Verhage M, Stiedl O: Display of individuality in avoidance behavior and risk assessment of inbred mice. (submitted)
  • Youn J, Hager T, Misane I, Pieneman AW, Jansen RF, Ögren SO, Meyer M, Stiedl O (2013) Central 5‐HT1A receptormediated modulation of heart rate dynamics and its adjustment by conditioned and unconditioned fear in mice. Brit J Pharmacol 170: 859‐870.
  • Eriksson TE, Holst S, Stan TL, Hager T, Sjögren B, Ögren SO, Svenningsson P, Stiedl O (2012) 5‐HT1A and 5‐HT7 receptors interact in the regulation of emotional learning: implications for the mechanisms of selective serotonin reuptake inhibitors. Neuropharmacology 63: 1150‐1160.
  • Eriksson TM, Alvarsson A, Stan TL, Zhang X, Hascup KN, Hascup ER, Kehr J, Gerhardt GA, Warner‐Schmidt J, Arango‐Lievano M, Kaplitt MG, Ögren SO, Greengard P, Svenningsson P (2013) Bidirectional regulation of emotional memory by 5‐HT1B receptors involves hippocampal p11. Molecular Psychiatry 18: 1096‐1105.
  • Stan TL, Alvarsson A, Branzell N, Sousa V, Svenningsson P (2013) Ketamine inhibits evoked glutamate release in vivo in hippocampus. (submitted)
  • Stan TL, Branzell N, Sousa V, Svenningsson P (2013) Antidepressant effects by chronic administration of lurasidone. (in preparation)
  • Hager T, Jansen RF, Pieneman AW, Manivannan SN, Golani I, Smit AB, Verhage M, Stiedl O: Display of individuality in avoidance behavior and risk assessment of inbred mice. Front. Behav. Neurosci. 8:314. doi:
10.3389/fnbeh.2014.00314 or, its link on Pubmed: www.ncbi.nlm.nih.gov/pubmed/25278853
  • Youn J, Ellenbroek BA, van Eck I, Roubos S, Verhage M, Stiedl O (2012) Finding the right motivation: Genotypedependent differences in effective reinforcements for spatial learning. Behavioural Brain Research 226: 397–403.
  • Stan TL, Alvarsson A, Branzell N, Sousa VC, Svenningsson P. NMDA receptor antagonists ketamine and Ro25-6981inhibit evoked release of glutamate in vivo.Translational Psychiatry, 2014; 4, e395.
  • Research teams

    To reach its objectives, the BrainTrain research program is composed of 5 scientific Research Teams, see list below, with 3 trainees each.
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  • The synaptic interactome

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  • Functional genomic of the synapse

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  • Synaptic plasticity

    In neuropsychiatric disorders associated with reduced cognitive abilities, such as age-related cognitive decline, but also mental retardation, the ability of synapses to alter their strength is strongly affected.
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  • Transmission and behavioral function

    The etiology of many disorders including age-related cognitive decline and neurodegenerative disorders such as dementia and Parkinson’s disease is still poorly understood.
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