Time-dependent involvement of the dorsal hippocampus in trace fear conditioning in mice

Authors

  • Ilga Misane,

    Corresponding author
    1. Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, Goettingen, Germany
    2. Department of Psychiatry, Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, Canada
    • Department of Psychiatry, Neuropsychiatry Research Unit, University of Saskatchewan, A 114 Medical Research Building, 103 Wiggins Road, Saskatoon, SK S7N 5E4, Canada
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  • Philip Tovote,

    1. Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, Goettingen, Germany
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  • Michael Meyer,

    1. Fractal Physiology Group, Max Planck Institute for Experimental Medicine, Goettingen, Germany
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  • Joachim Spiess,

    1. Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, Goettingen, Germany
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  • Sven Ove Ögren,

    1. Division of Behavioral Neuroscience, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
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  • Oliver Stiedl

    1. Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, Goettingen, Germany
    2. Division of Behavioral Neuroscience, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    3. Center for Neurogenomics and Cognitive Research and Institute of Neurosciences, Vrije University Amsterdam, The Netherlands
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Abstract

Hippocampal and amygdaloid neuroplasticity are important substrates for Pavlovian fear conditioning. The hippocampus has been implicated in trace fear conditioning. However, a systematic investigation of the significance of the trace interval has not yet been performed. Therefore, this study analyzed the time-dependent involvement of N-methyl-D-aspartate (NMDA) receptors in the dorsal hippocampus in one-trial auditory trace fear conditioning in C57BL/6J mice. The NMDA receptor antagonist APV was injected bilaterally into the dorsal hippocampus 15 min before training. Mice were exposed to tone (conditioned stimulus [CS]) and footshock (unconditioned stimulus [US]) in the conditioning context without delay (0 s) or with CS-US (trace) intervals of 1–45 s. Conditioned auditory fear was determined 24 h after training by the assessment of freezing and computerized evaluation of inactivity in a new context; 2 h later, context-dependent memory was tested in the conditioning context. NMDA receptor blockade by APV markedly impaired conditioned auditory fear at trace intervals of 15 s and 30 s, but not at shorter trace intervals. A 45-s trace interval prevented the formation of conditioned tone-dependent fear. Context-dependent memory was always impaired by APV treatment independent of the trace interval. The results indicate that the dorsal hippocampus and its NMDA receptors play an important role in auditory trace fear conditioning at trace intervals of 15–30-s length. In contrast, NMDA receptors in the dorsal hippocampus are unequivocally involved in contextual fear conditioning independent of the trace interval. The results point at a time-dependent role of the dorsal hippocampus in encoding of noncontingent explicit stimuli. Preprocessing of long CS-US contingencies in the hippocampus appears to be important for the final information processing and execution of fear memories through amygdala circuits. © 2005 Wiley-Liss, Inc.

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