Time-dependent involvement of the dorsal hippocampus in trace fear conditioning in mice
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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.
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The amygdala, through connections with the hippocampus, thalamus, mPFC, and ACC, is involved in control of the encoding and retrieval of affective memories and the physical expression of emotions during the waking state.
“the amygdala, thanks to the connections with the hippocampus, thalamus, mPFC, and ACC, is involved in control of the encoding and retrieval of affective memories and the physical expression of emotions during the waking state”
From The Functional Role of Dreaming in Emotional Processes (2019) · cites this paper as Misane et al., 2005
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Self-citation
- Authors
- Misane, I., Tovote, P., Meyer, M., Spiess, J., Ögren, S. O., & Stiedl, O.
- Affiliations
- University of Saskatchewan (CA)
- Max Planck Institute of Experimental Medicine (DE)
- Karolinska Institutet (SE)
- Corresponding author
- Misane, Ilga
- Venue
- Hippocampus
- Publisher
- Wiley
- Published
- 2005-01
- Volume
- 15
- Issue
- 4
- Pages
- 418-426
- ISSN
- 1050-9631 (ISSN-L)
- 1098-1063
- OpenAlex
- W2131618009
- Cited by
- 183
- References
- 45
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 11 · 2020: 10 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 14 · 2015: 8 · 2014: 9 · 2013: 11 · 2012: 9
- FWCI
- 6.10
- Type
- journal article
- Language
- en
- Open access
- Locations
- Hippocampus (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- dorsal hippocampus, trace fear conditioning, NMDA receptor, APV, trace interval, auditory fear, contextual fear memory, fear memory consolidation, hippocampal-amygdala interaction, fear conditioning
- MeSH terms
- Acoustic Stimulation, Amygdala, Animals, Conditioning, Psychological, Cues, Fear, Hippocampus, Learning, Male, Memory, Mice, Inbred C57BL, Neural Pathways, Synaptic Transmission, Neuronal Plasticity, Time Factors, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Excitatory Amino Acid Antagonists, Glutamic Acid, Mice
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