Altitude acclimatization improves submaximal cognitive performance in mice and involves an imbalance of the cholinergic system

J Appl Physiol (1985). 2013 Jun 15;114(12):1705-16. doi: 10.1152/japplphysiol.01298.2012. Epub 2013 Apr 18.


The aim of this work was to reveal a hypothetical improvement of cognitive abilities in animals acclimatized to altitude and performing under ground level conditions, when looking at submaximal performance, once seen that it was not possible when looking at maximal scores. We modified contrasted cognitive tasks (object recognition, operant conditioning, eight-arm radial maze, and classical conditioning of the eyeblink reflex), increasing their complexity in an attempt to find performance differences in acclimatized animals vs. untrained controls. In addition, we studied, through immunohistochemical quantification, the expression of choline acetyltransferase and acetyl cholinesterase, enzymes involved in the synthesis and degradation of acetylcholine, in the septal area, piriform and visual cortexes, and the hippocampal CA1 area of animals submitted to acute hypobaric hypoxia, or acclimatized to this simulated altitude, to find a relationship between the cholinergic system and a cognitive improvement due to altitude acclimatization. Results showed subtle improvements of the cognitive capabilities of acclimatized animals in all of the tasks when performed under ground-level conditions (although not before 24 h), in the three tasks used to test explicit memory (object recognition, operant conditioning in the Skinner box, and eight-arm radial maze) and (from the first conditioning session) in the classical conditioning task used to evaluate implicit memory. An imbalance of choline acetyltransferase/acetyl cholinesterase expression was found in acclimatized animals, mainly 24 h after the acclimatization period. In conclusion, altitude acclimatization improves cognitive capabilities, in a process parallel to an imbalance of the cholinergic system.

Keywords: ACh immunohistochemistry; classical conditioning; mice; operant conditioning; simulated altitude; spatial learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acclimatization / physiology*
  • Acetylcholine / metabolism*
  • Acetylcholinesterase / metabolism*
  • Altitude*
  • Animals
  • Behavior, Animal / physiology
  • Choline O-Acetyltransferase / metabolism*
  • Cognition / physiology*
  • Conditioning, Operant / physiology
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Hypoxia / metabolism
  • Hypoxia / physiopathology
  • Male
  • Memory / physiology
  • Mice
  • Mice, Inbred C57BL
  • Psychomotor Performance / physiology*
  • Septum of Brain / metabolism
  • Septum of Brain / physiology
  • Task Performance and Analysis
  • Visual Cortex / metabolism
  • Visual Cortex / physiology


  • Choline O-Acetyltransferase
  • Acetylcholinesterase
  • Acetylcholine