Memory consolidation for contextual and auditory fear conditioning is dependent on protein synthesis, PKA, and MAP kinase - PubMed (original) (raw)
. 1999 Mar-Apr;6(2):97-110.
Affiliations
- PMID: 10327235
- PMCID: PMC311283
Memory consolidation for contextual and auditory fear conditioning is dependent on protein synthesis, PKA, and MAP kinase
G E Schafe et al. Learn Mem. 1999 Mar-Apr.
Abstract
Fear conditioning has received extensive experimental attention. However, little is known about the molecular mechanisms that underlie fear memory consolidation. Previous studies have shown that long-term potentiation (LTP) exists in pathways known to be relevant to fear conditioning and that fear conditioning modifies neural processing in these pathways in a manner similar to LTP induction. The present experiments examined whether inhibition of protein synthesis, PKA, and MAP kinase activity, treatments that block LTP, also interfere with the consolidation of fear conditioning. Rats were injected intraventricularly with Anisomycin (100 or 300 microg), Rp-cAMPS (90 or 180 microg), or PD098059 (1 or 3 microg) prior to conditioning and assessed for retention of contextual and auditory fear memory both within an hour and 24 hr later. Results indicated that injection of these compounds selectively interfered with long-term memory for contextual and auditory fear, while leaving short-term memory intact. Additional control groups indicated that this effect was likely due to impaired memory consolidation rather than to nonspecific effects of the drugs on fear expression. Results suggest that fear conditioning and LTP may share common molecular mechanisms.
Figures
Figure 1
Outline of general behavioral procedures.
Figure 2
Representative cannula placement in the lateral ventricle (LV). (Arrows) Point of entry. Cresyl violet dye can be seen lining the ventricle ependyma.
Figure 3
(A) (Top) Mean (±
s.e.
) percent freezing for context STM in rats injected with ACSF (█; n = 10), 300 μg Anisomycin (shaded triangles; n = 9), or 100 μg Anisomycin (▵; n = 7). (Middle) Mean (±
s.e.
) freezing for context LTM in the same rats. (Bottom) Mean (±
s.e.
) percent context LTM for ACSF- and Anisomycin-injected rats. (B) (Top) Mean (±
s.e.
) percent freezing during the baseline period prior to the first trial in the STM tone test. (Middle) Mean (±
s.e.
) percent freezing during the baseline period prior to the first trial in the LTM tone test (C) (Top) Mean (±
s.e.
) percent freezing for tone STM in unpaired controls (□; n = 8), and rats injected with ACSF (█), 300 μg Anisomycin (shaded triangles), or 100 μg Anisomycin (▵). (Middle) Mean (±
s.e.
) freezing for tone LTM in the same rats. (Bottom) Mean (±
s.e.
) percent tone LTM for ACSF- and Anisomycin-injected rats, and unpaired controls.
Figure 4
(A) (Top) Mean (±
s.e.
) percent freezing for context STM in rats injected with ACSF (█; n = 9), 180 μg Rp-cAMPS (shaded triangles; n = 7), or 90 μg Rp-cAMPS (▵; n = 8). (Middle) Mean (±
s.e.
) freezing for context LTM in the same rats. (Bottom) Mean (±
s.e.
) percent context LTM for ACSF- and Rp-cAMPS-injected rats. (B) (Top) Mean (±
s.e.
) percent freezing during the baseline period prior to the first trial in the STM tone test. (Middle) Mean (±
s.e.
) percent freezing during the baseline period prior to the first trial in the LTM tone test. (C) (Top) Mean (±
s.e.
) percent freezing for tone STM in rats injected with ACSF (█), 180 μg Rp-cAMPS (shaded triangles), or 90 μg Rp-cAMPS (▵). (Middle) Mean (±
s.e.
) freezing for tone LTM in the same rats. (Bottom) Mean (±
s.e.
) percent tone LTM for ACSF- and Rp-cAMPS-injected rats.
Figure 5
(A) (Top) Mean (±
s.e.
) percent freezing for context STM in rats injected with DMSO (█; n = 11), 3 μg PD098059 (shaded triangles; n = 9), or 1 μg PD098059 (▵; n = 8). (Middle) Mean (±
s.e.
) freezing for context LTM in the same rats. (Bottom) Mean (±
s.e.
) percent context LTM for DMSO- and PD098059-injected rats. (B) (Top) Mean (±
s.e.
) percent freezing during the baseline period prior to the first trial in the STM tone test. (Middle) Mean (±
s.e.
) percent freezing during the baseline period prior to the first tone trial in the LTM tone test. (C) (Top) Mean (±
s.e.
) percent freezing for tone STM in unpaired rats (□; n = 8), and rats injected with DMSO (█), 3 μg PD098059 (shaded triangles), or 1 μg PD098059 (▵). (Middle) Mean (±
s.e.
) freezing for tone LTM in the same rats. (Bottom) Mean (±
s.e.
) percent tone LTM for DMSO- and PD098059-injected rats and unpaired controls.
Figure 6
(A) Mean (±
s.e.
) percent freezing for context (top) and tone (bottom) LTM following re-conditioning in rats injected with ACSF (█), 300 μg Anisomycin (shaded triangles), 180 μg Rp-cAMPS (shaded circles), or 3 μg PD098059 (○). Rats were tested for context and tone memory 24 hr after reconditioning. (B) Mean (±
s.e.
) percent freezing for context (top) and tone (bottom) STM in rats injected with ACSF (█; n = 8), 300 μg Anisomycin (shaded triangles; n = 8), 180 μg Rp-cAMPS (shaded circles; n = 8), or 3 μg PD098059 (○; n = 8) 24 hr prior to conditioning. Rats were evaluated for tone and context memory either 30 or 60 min following conditioning, respectively.
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