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Memory retrieval impairment induced by hippocampal CA3 lesions is blocked by adrenocortical suppression

B Roozendaal1, R G Phillips, A E Power

  • 1Center for the Neurobiology of Learning and Memory, and Department of Neurobiology and Behavior, University of California, Irvine, California 92697-3800, USA. broozend@uci.edu

Nature Neuroscience
|November 20, 2001
PubMed

Insights

Hippocampal damage impairs spatial memory retrieval in rats. Inhibiting corticosterone, a stress hormone, with metyrapone reversed these memory deficits, suggesting a critical role for the HPA axis.

Area of Science:

  • Neuroscience
  • Memory Research
  • Endocrinology

Background:

  • Hippocampal lesions, particularly in the CA3 subfield, are known to impair spatial memory retrieval in rats.
  • Hippocampal damage also leads to disinhibition of the hypothalamic-pituitary-adrenocortical (HPA) axis, increasing stress hormone levels.

Purpose of the Study:

  • To investigate the role of elevated adrenocortical activity in mediating memory retrieval deficits following hippocampal damage.
  • To determine if inhibiting corticosterone synthesis can ameliorate lesion-induced memory impairments.

Main Methods:

  • Rats with partial hippocampal CA3 lesions were used.
  • Metyrapone, a synthesis inhibitor of corticosterone, was administered before water-maze retention testing.
  • Plasma corticosterone levels and memory retrieval performance were assessed.

Main Results:

  • CA3 lesions resulted in impaired spatial memory retrieval and elevated plasma corticosterone levels.
  • Administration of metyrapone attenuated the lesion-induced increase in corticosterone.
  • Blocking the rise in corticosterone levels with metyrapone prevented the memory retrieval deficits.

Conclusions:

  • Elevated adrenocortical activity, specifically increased corticosterone, is critical for mediating memory retrieval deficits caused by hippocampal damage.
  • The HPA axis plays a significant role in the cognitive impairments associated with hippocampal injury.

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