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Dorsal hippocampus and classical fear conditioning to tone and context in rats: effects of local NMDA-receptor blockade and stimulation.
Hippocampus. 2003; 13(6):657-75.H

Abstract

Consistent with the importance of the hippocampus in learning more complex stimulus relations, but not in simple associative learning, the dorsal hippocampus has commonly been implicated in classical fear conditioning to context, but not to discrete stimuli, such as a tone. In particular, a specific and central role in contextual fear conditioning has been attributed to mechanisms mediated by dorsal hippocampal N-methyl-D-aspartate (NMDA)-type glutamate receptors. The present study characterized the effects of blockade or tonic stimulation of dorsal hippocampal NMDA receptors by bilateral local infusion of the noncompetitive NMDA receptor antagonist MK-801 (dizocilpine maleate; 6.25 microg/side) or of NMDA (0.7 microg/side), respectively, on classical fear conditioning to tone and context in Wistar rats. Freezing was used to measure conditioned fear. Regardless of whether conditioning was conducted with tone-shock pairings or unsignaled footshocks (background or foreground contextual conditioning), both NMDA and MK-801 infusion before conditioning resulted in reduced freezing during subsequent exposure to the conditioning context. Freezing during subsequent tone presentation in a new context, normally resulting from conditioning with tone-shock pairings, was not impaired by MK-801 but was strongly reduced by NMDA infusion before conditioning; this freezing was also reduced by NMDA infusion before tone presentation (in an experiment involving NMDA infusions before conditioning and subsequent tone presentation to assess the role of state-dependent learning). It was assessed whether unspecific infusion effects (altered sensorimotor functions, state dependency) or infusion-induced dorsal hippocampal damage contributed to the observed reductions in conditioned freezing. Our data suggest that formation of fear conditioning to context, but not tone, requires NMDA receptor-mediated mechanisms in the dorsal hippocampus. As indicated by the effects of NMDA, some dorsal hippocampal processes may also contribute to fear conditioning to tone. The role of the dorsal hippocampus and local NMDA receptor-mediated processes in fear conditioning to tone and context is discussed in comparison with ventral hippocampal processes.

Authors+Show Affiliations

Bast T
Behavioral Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schwerzenbach, Switzerland.
Zhang WN
No affiliation info available
Feldon J
No affiliation info available

MeSH

Acoustic StimulationAnimalsAvoidance LearningConditioning, PsychologicalDizocilpine MaleateExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsFearGlutamic AcidHippocampusMaleN-MethylaspartateNeuronsRatsRats, WistarReceptors, N-Methyl-D-AspartateSynapsesSynaptic Transmission

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12962312

Citation

Bast, Tobias, et al. "Dorsal Hippocampus and Classical Fear Conditioning to Tone and Context in Rats: Effects of Local NMDA-receptor Blockade and Stimulation." Hippocampus, vol. 13, no. 6, 2003, pp. 657-75.
Bast T, Zhang WN, Feldon J. Dorsal hippocampus and classical fear conditioning to tone and context in rats: effects of local NMDA-receptor blockade and stimulation. Hippocampus. 2003;13(6):657-75.
Bast, T., Zhang, W. N., & Feldon, J. (2003). Dorsal hippocampus and classical fear conditioning to tone and context in rats: effects of local NMDA-receptor blockade and stimulation. Hippocampus, 13(6), 657-75.
Bast T, Zhang WN, Feldon J. Dorsal Hippocampus and Classical Fear Conditioning to Tone and Context in Rats: Effects of Local NMDA-receptor Blockade and Stimulation. Hippocampus. 2003;13(6):657-75. PubMed PMID: 12962312.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dorsal hippocampus and classical fear conditioning to tone and context in rats: effects of local NMDA-receptor blockade and stimulation. AU - Bast,Tobias, AU - Zhang,Wei-Ning, AU - Feldon,Joram, PY - 2003/9/10/pubmed PY - 2003/12/13/medline PY - 2003/9/10/entrez SP - 657 EP - 75 JF - Hippocampus JO - Hippocampus VL - 13 IS - 6 N2 - Consistent with the importance of the hippocampus in learning more complex stimulus relations, but not in simple associative learning, the dorsal hippocampus has commonly been implicated in classical fear conditioning to context, but not to discrete stimuli, such as a tone. In particular, a specific and central role in contextual fear conditioning has been attributed to mechanisms mediated by dorsal hippocampal N-methyl-D-aspartate (NMDA)-type glutamate receptors. The present study characterized the effects of blockade or tonic stimulation of dorsal hippocampal NMDA receptors by bilateral local infusion of the noncompetitive NMDA receptor antagonist MK-801 (dizocilpine maleate; 6.25 microg/side) or of NMDA (0.7 microg/side), respectively, on classical fear conditioning to tone and context in Wistar rats. Freezing was used to measure conditioned fear. Regardless of whether conditioning was conducted with tone-shock pairings or unsignaled footshocks (background or foreground contextual conditioning), both NMDA and MK-801 infusion before conditioning resulted in reduced freezing during subsequent exposure to the conditioning context. Freezing during subsequent tone presentation in a new context, normally resulting from conditioning with tone-shock pairings, was not impaired by MK-801 but was strongly reduced by NMDA infusion before conditioning; this freezing was also reduced by NMDA infusion before tone presentation (in an experiment involving NMDA infusions before conditioning and subsequent tone presentation to assess the role of state-dependent learning). It was assessed whether unspecific infusion effects (altered sensorimotor functions, state dependency) or infusion-induced dorsal hippocampal damage contributed to the observed reductions in conditioned freezing. Our data suggest that formation of fear conditioning to context, but not tone, requires NMDA receptor-mediated mechanisms in the dorsal hippocampus. As indicated by the effects of NMDA, some dorsal hippocampal processes may also contribute to fear conditioning to tone. The role of the dorsal hippocampus and local NMDA receptor-mediated processes in fear conditioning to tone and context is discussed in comparison with ventral hippocampal processes. SN - 1050-9631 UR - https://www.unboundmedicine.com/medline/citation/12962312/Dorsal_hippocampus_and_classical_fear_conditioning_to_tone_and_context_in_rats:_effects_of_local_NMDA_receptor_blockade_and_stimulation_ DB - PRIME DP - Unbound Medicine ER -