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Infant avoidance training alters cellular activation patterns in prefronto-limbic circuits during adult avoidance learning: I. Cellular imaging of neurons expressing the synaptic plasticity early growth response protein 1 (Egr1)

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Abstract

Both positive feedback learning and negative feedback learning are essential for adapting and optimizing behavioral performance. There is increasing evidence in humans and animals that the ability of negative feedback learning emerges postnatally. Our work in rats, using a two-way active avoidance task (TWA) as an experimental paradigm for negative feedback learning, revealed that medial and lateral prefrontal regions of infant rats undergo dramatic synaptic reorganization during avoidance training, resulting in improved avoidance learning in adulthood. The aim of this study was to identify changes of cellular activation patterns during the course of training and in relation to infant pretraining. We applied a quantitative cellular imaging technique using the immunocytochemical detection of the activity marker early growth response protein 1 (Egr1) as a candidate contributing to learning-induced synaptic plasticity. We found region-specific cellular activity patterns, which indicate that during the acquisition phase, Egr1 expression is specifically elevated in cellular ensembles of the orbitofrontal, dorsal anterior cingulate and hippocampal CA1 region. During memory retrieval Egr1 expression is elevated in cellular ensembles of the dentate gyrus. Moreover, we, for the first time, show here that TWA training during infancy alters adult learning- and memory-related patterns of Egr1 expression in these brain regions. It is tempting to speculate that during infant learning, specific Egr1-expressing cellular ensembles are “tagged” representing long-term memory formation, and that these cell ensembles may be reactivated during adult learning.

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Acknowledgements

We thank Madeleine Stiefel for helping with editorial work. This work was funded by the Bundesministerium für Bildung und Forschung, Grant no: 01KR1304B (TRANSGEN) and Grant No: 01KR1207D (UBICA).

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Author notes

  1. Nicole Gröger and Anja Mannewitz contributed equally as first authors.

  2. Gerd Poeggel and Katharina Braun contributed equally as senior authors.

Authors and Affiliations

  1. Department of Zoology/Developmental Neurobiology, Otto von Guericke University, Leipziger Straße 44, Bldg. 91, 39120, Magdeburg, Germany

    Nicole Gröger, Anja Mannewitz, Tony Fernando de Schultz, Katja Guttmann & Katharina Braun

  2. FG Epigenetics and Structural Plasticity, Otto von Guericke University, Magdeburg, Germany

    Jörg Bock

  3. Institute for Biology, Human Biology, University of Leipzig, 04103, Leipzig, Germany

    Gerd Poeggel

  4. Center for Behavioral Brain Science (CBBS), Magdeburg, Germany

    Jörg Bock & Katharina Braun

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  1. Nicole Gröger
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Correspondence to Katharina Braun.

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Gröger, N., Mannewitz, A., Bock, J. et al. Infant avoidance training alters cellular activation patterns in prefronto-limbic circuits during adult avoidance learning: I. Cellular imaging of neurons expressing the synaptic plasticity early growth response protein 1 (Egr1). Brain Struct Funct 222, 3639–3651 (2017). https://doi.org/10.1007/s00429-017-1423-1

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