Impairment of conditioned contextual fear of C57BL/6J mice by intracerebral injections of the NMDA receptor antagonist APV

Stiedl, Oliver; Birkenfeld, Karin; Palve, Markki; Spiess, Joachim

doi:10.1016/s0166-4328(00)00269-2

Cited by 89 publications

(84 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This suggestion is confirmed directly by the present finding that blockade of NMDA receptors in the rat dorsal hippocampus by local infusion of the noncompetitive antagonist MK-801 impaired the formation of foreground and background contextual fear conditioning, while leaving fear conditioning to a tone intact. Similar results were obtained in a recent study after infusion of APV into the dorsal hippocampus of mice (Stiedl et al, 2000). In our previous study, MK-801 infusion into the ventral hippocampus of rats also induced such selective effects on fear conditioning to a context (Zhang et al, 2001).…”

Section: Fear Conditioning To Contextsupporting

confidence: 91%

“…Foreground contextual fear conditioning, i.e., fear conditioning to a context in which unsignaled shocks were presented, has been found to be impaired by dorsal hippocampal lesions in rats (Kim et al, 1993;Young et al, 1994), even though another study did not confirm this effect (Phillips and LeDoux, 1994), and by dorsal hippocampal infusion of the competitive NMDA-receptor antagonist D,L-2-amino-5-phosphonovalerate (APV) in both rats (Young et al, 1994) and mice (Stiedl et al, 2000). Experiment 1 was carried out to confirm the requirement of dorsal hippocampal NMDA receptors, as well as to examine the effect of tonic stimulation of these receptors, in foreground contextual fear conditioning.…”

Section: Experiments 1: Foreground Contextual Fear Conditioning After mentioning

confidence: 99%

“…However, only in mice has intact fear conditioning to a tone actually been demonstrated after blockade of dorsal hippocampal NMDA receptors by local APV infusion (Stiedl et al, 2000). Experiment 2 further examined the effects of altered NMDA receptor-mediated signaling in the dorsal hippocampus on simple fear conditioning to tone.…”

Section: Experiments 2: Fear Conditioning To a Tone After Dorsal Hippomentioning

confidence: 99%

“…It is still commonly held, however, that the dorsal hippocampus, which indeed may differ functionally from the ventral hippocampus (Moser and Moser, 1998;Zhang et al, 2002), contributes to contextual fear conditioning by supporting a unified context representation, but is not required for fear conditioning to tone (Fanselow, 2000;Gale et al, 2001;Rudy and O'Reilly, 2001;Wallenstein and Vago, 2001; but see Maren et al, 1997). In particular, fear conditioning to context, similar to spatial and episodic-like learning (Morris et al, 1989;Steele and Morris, 1999;Lee and Kesner, 2002; but see Cain, 1997), has been suggested to require processes mediated by N-methyl-D-aspartate (NMDA)-type glutamate receptors in the dorsal hippocampus, and prevalent concepts of fear conditioning to context imply a central contribution of NMDA receptor-mediated synaptic plasticity in the dorsal hippocampus to context representa-tion Young et al, 1994;Anagnostaras et al, 2001;Stiedl et al, 2000;Gale et al, 2001). However, although we recently provided respective data for the ventral hippocampus (Zhang et al, 2001), it remains to be demonstrated directly that blockade of NMDA receptors in the rat dorsal hippocampus impairs only fear conditioning to context, but not to tone.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dorsal hippocampus and classical fear conditioning to tone and context in rats: Effects of local NMDA‐receptor blockade and stimulation

2003

View full text Add to dashboard Cite

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 g/side) or of NMDA (0.7 g/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.

show abstract

Section: Fear Conditioning To Contextsupporting

confidence: 91%

Section: Experiments 1: Foreground Contextual Fear Conditioning After mentioning

confidence: 99%

Section: Experiments 2: Fear Conditioning To a Tone After Dorsal Hippomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dorsal hippocampus and classical fear conditioning to tone and context in rats: Effects of local NMDA‐receptor blockade and stimulation

2003

View full text Add to dashboard Cite

show abstract

“…The latter requires an intact hippocampal formation in addition to the involvement of the basolateral amygdala complex (Kim and Fanselow, 1992;Rudy et al, 2004). Pharmacological blockade of NMDA receptors or local protein synthesis within the dorsal hippocampus significantly impaired acquisition and consolidation of contextual fear memory in a background conditioning task (Stiedl et al, 2000). Recently, we extended this observation to foreground conditioning tasks with C57BL/6N mice (i.e., the background strain of TRPV1 mutants).…”

Section: Discussionmentioning

confidence: 87%

Reduced Anxiety, Conditioned Fear, and Hippocampal Long-Term Potentiation in Transient Receptor Potential Vanilloid Type 1 Receptor-Deficient Mice

Marsch¹,

Foeller²,

Rammes³

et al. 2007

J. Neurosci.

315

230

View full text Add to dashboard Cite

The transient receptor potential vanilloid type 1 channel (TRPV1) (formerly called vanilloid receptor VR1) is known for its key role of functions in sensory nerves such as perception of inflammatory and thermal pain. Much less is known about the physiological significance of the TRPV1 expression in the brain. Here we demonstrate that TRPV1 knock-out mice (TRPV1-KO) show less anxiety-related behavior in the light-dark test and in the elevated plus maze than their wild-type littermates with no differences in locomotion. Furthermore, TRPV1-KO mice showed less freezing to a tone after auditory fear conditioning and stress sensitization. This reduction of conditioned and sensitized fear could not be explained by alterations in nociception. Also, tone perception per se was unaffected, as revealed by determination of auditory thresholds through auditory brainstem responses and distortion-product otoacoustic emissions. TRPV1-KO showed also less contextual fear if assessed 1 d or 1 month after strong conditioning protocols. These impairments in hippocampusdependent learning were mirrored by a decrease in long-term potentiation in the Schaffer collateral-commissural pathway to CA1 hippocampal neurons. Our data provide first evidence for fear-promoting effects of TRPV1 with respect to both innate and conditioned fear and for a decisive role of this receptor in synaptic plasticity.

show abstract

Emotional Plasticity

Schafe

LeDoux

2002

Stevens' Handbook of Experimental Psychology

View full text Add to dashboard Cite

Pavlovian fear conditioning has emerged as a leading behavioral paradigm to study emotion systems in the brain. In this chapter, we first provide a brief historical survey of efforts to pinpoint emotional circuits in the brain. We then review what has been learned about fear conditioning circuitry at the systems, cellular, and biochemical/molecular levels, primarily in rodents. We then discuss how this knowledge has been applied to the fear system of the human brain.

show abstract

Impairment of conditioned contextual fear of C57BL/6J mice by intracerebral injections of the NMDA receptor antagonist APV

Cited by 89 publications

References 39 publications

Dorsal hippocampus and classical fear conditioning to tone and context in rats: Effects of local NMDA‐receptor blockade and stimulation

Dorsal hippocampus and classical fear conditioning to tone and context in rats: Effects of local NMDA‐receptor blockade and stimulation

Reduced Anxiety, Conditioned Fear, and Hippocampal Long-Term Potentiation in Transient Receptor Potential Vanilloid Type 1 Receptor-Deficient Mice

Emotional Plasticity

Contact Info

Product

Resources

About