Hippocampal theta, gamma, and theta-gamma coupling: effects of aging, environmental change, and cholinergic activation

J Neurophysiol. 2013 Apr;109(7):1852-65. doi: 10.1152/jn.00409.2012. Epub 2013 Jan 9.


Hippocampal theta and gamma oscillations coordinate the timing of multiple inputs to hippocampal neurons and have been linked to information processing and the dynamics of encoding and retrieval. One major influence on hippocampal rhythmicity is from cholinergic afferents. In both humans and rodents, aging is linked to impairments in hippocampus-dependent function along with degradation of cholinergic function. Cholinomimetics can reverse some age-related memory impairments and modulate oscillations in the hippocampus. Therefore, one would expect corresponding changes in these oscillations and possible rescue with the cholinomimetic physostigmine. Hippocampal activity was recorded while animals explored a familiar or a novel maze configuration. Reexposure to a familiar situation resulted in minimal aging effects or changes in theta or gamma oscillations. In contrast, exploration of a novel maze configuration increased theta power; this was greater in adult than old animals, although the deficit was reversed with physostigmine. In contrast to the theta results, the effects of novelty, age, and/or physostigmine on gamma were relatively weak. Unrelated to the behavioral situation were an age-related decrease in the degree of theta-gamma coupling and the fact that physostigmine lowered the frequency of theta in both adult and old animals. The results indicate that age-related changes in gamma and theta modulation of gamma, while reflecting aging changes in hippocampal circuitry, seem less related to aging changes in information processing. In contrast, the data support a role for theta and the cholinergic system in encoding and that hippocampal aging is related to impaired encoding of new information.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Brain Waves
  • Cholinesterase Inhibitors / pharmacology*
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Hippocampus / physiology*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology*
  • Physostigmine / pharmacology*
  • Rats
  • Rats, Inbred F344
  • Theta Rhythm*


  • Cholinesterase Inhibitors
  • Physostigmine