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 Projects

 Learning-induced Plasticity

W. Tischmeyer, H. Schicknick, C. Theuerkauf, K.-H. Smalla

Previous studies focussed on mechanisms of learning-induced plasticity in the hippocampus. Expression analysis and antisense intervention targeting this brain region revealed the functional significance of inducible transcription factors for visual discrimination learning in rats (reviewed in Tischmeyer & Grimm 1999). At present, cortical mechanisms of learning-induced plasticity are studied in gerbils and mice using an auditory discrimination paradigm. Behavioural pharmacological studies revealed that shortly after learning at least two protein synthesis-dependent processes in the auditory cortex control long-term memory formation (Kraus et al. 2002; Tischmeyer et al. 2003). While one process is required for initial retention of the newly acquired memory, another process, involving signalling mediated by the protein kinase mTOR, seems to induce additional mechanisms that facilitate memory consolidation on subsequent days.

Putative role of mTOR-mediated signaling in neurons Putative role of mTOR-mediated signaling in neurons: facilitation of synaptic plasticity by coupling synaptic events to protein synthesis/degradation and the dynamics of cytoskeletal components. mTOR controls, amongst others, the rapamycin-sensitive phosphorylation of key components of translational regulation, such as ribosomal S6 protein kinase (p70S6K) and eIF4E-binding protein 1 (4E-BP1). Growth factors and neuro­transmitters (e.g. dopamine) are candidates for a transsynaptic induction of these pathways.

In collaboration with other labs within the framework of the “Sonder­forschungsbereich 779”, our research efforts are currently aimed at identifying candidate neurotransmitters, intracellular pathways, and protein components with functional relevance for cortex-dependent learning. So far, the results suggest that maintenance of the memory trace and its retrievability up to the next day requires glutamatergic as well as dopaminergic activities in the auditory cortex (Schicknick & Tischmeyer 2006; Schicknick et al. 2012), whereas processes that facilitate anterograde memory formation are notably induced by dopaminergic mechanisms (Schicknick et al. 2008, 2012). Proteomic analysis performed after pharmacologically induced dopaminergic activity in the auditory cortex revealed changes in the patterns of neural proteins in multiple brain regions. These regions also showed synaptic proteome changes after auditory discrimination learning (Kähne et al. 2012). The predominant involvement of cytoskeletal and scaffolding proteins implies effects on synaptic cytomatrices that might facilitate subsequent learning-induced plastic rearrangements in synaptic structure and function.

 

Cooperations

International

Vrije Universiteit Amsterdam, The Netherlands (K.W. Li)

National

OvGU Magdeburg

IPT (D.C. Dieterich); IEIM (T. Kähne, M. Naumann); IBMI (S. Kropf); IBIO (O. Stork)

DZNE Magdeburg

FG Funktionales Neuroimaging (F. Angenstein)

LIN Magdeburg

Dept. Neurochemistry & Molecular Biology (E.D. Gundelfinger, C.I. Seidenbecher); Dept. Systems Physiology of Learning (F.W. Ohl, A. Kolodziej); Dept. Auditory Learning & Speech (H. Scheich); Special Lab Behavioral Pharmacology (W. Wetzel), Special Lab Electron and laserscanning microscopy (W. Zuschratter)

 

Relevant Publications

Research articles

Grimm R, Tischmeyer W (1997) Complex patterns of immediate early gene induction in rat brain following brightness discrimination training and pseudotraining. Behav Brain Res 84:109-116.

Grimm R, Schicknick H, Riede I, Gundelfinger ED, Herdegen T, Zuschratter W, Tischmeyer W (1997) Suppression of c-fos induction in rat brain impairs retention of a brightness discrimination reaction. Learn Mem 3:402-413.

Tischmeyer W (2000) Antisense oligonucleotides: preparation and in vivo application to rat brain. Methods Enzymol 314:275-290.

Kraus M, Schicknick H, Wetzel W, Ohl F, Staak S, Tischmeyer W (2002) Memory consolidation for the discrimination of frequency-modulated tones in Mongolian gerbils is sensitive to protein-synthesis inhibitors applied to the auditory cortex. Learn Mem 9:293-303.

Tischmeyer W, Schicknick H, Kraus M, Seidenbecher CI, Staak S, Scheich H, Gundelfinger ED (2003) Rapamycin-sensitive signalling in long-term consolidation of auditory cortex-dependent memory. Eur J Neurosci 18:942-950.

Schicknick H, Tischmeyer W (2006) Consolidation of auditory cortex-dependent memory requires N-methyl-D-aspartate receptor activation. Neuropharmacology 50:671-676.

Schicknick H, Schott BH, Budinger E, Smalla KH, Riedel A, Seidenbecher CI, Scheich H, Gundelfinger ED, Tischmeyer W (2008) Dopaminergic modulation of auditory cortex-dependent memory consolidation through mTOR. Cereb Cortex 18:2646-2658.

Schicknick H, Reichenbach N, Smalla KH, Scheich H, Gundelfinger ED, Tischmeyer W (2012) Dopamine modulates memory consolidation of discrimination learning in the auditory cortex. Eur J Neurosci 35:763-774.

Kähne T, Kolodziej A, Smalla KH, Eisenschmidt E, Haus UU, Weismantel R, Kropf S, Wetzel W, Ohl FW, Tischmeyer W, Naumann M, Gundelfinger ED (2012) Synaptic proteome changes in mouse brain regions upon auditory discrimination learning. Proteomics 12:2433-2444.

Kemp A, Tischmeyer W, Manahan-Vaughan D (2013) Learning-facilitated long-term depression requires activation of the immediate early gene, c-fos, and is transcription dependent. Behav Brain Res, 2013 Apr 30. doi: 10.1016/j.bbr.2013.04.036.

Reviews

Tischmeyer W, Grimm R (1999) Activation of immediate early genes and memory formation. Cell Mol Life Sci 55:564-574.

Scheich H, Brechmann A, Brosch M, Budinger E, Ohl FW, Selezneva E, Stark H, Tischmeyer W, Wetzel W (2011) Behavioral semantics of learning and crossmodal processing in auditory cortex: the semantic processor concept. Hear Res 271:3-15.

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