Different theta frameworks coexist in the rat hippocampus and are coordinated during memory-guided and novelty tasks

Elife. 2020 Jul 20;9:e57313. doi: 10.7554/eLife.57313.

Abstract

Hippocampal firing is organized in theta sequences controlled by internal memory processes and by external sensory cues, but how these computations are coordinated is not fully understood. Although theta activity is commonly studied as a unique coherent oscillation, it is the result of complex interactions between different rhythm generators. Here, by separating hippocampal theta activity in three different current generators, we found epochs with variable theta frequency and phase coupling, suggesting flexible interactions between theta generators. We found that epochs of highly synchronized theta rhythmicity preferentially occurred during behavioral tasks requiring coordination between internal memory representations and incoming sensory information. In addition, we found that gamma oscillations were associated with specific theta generators and the strength of theta-gamma coupling predicted the synchronization between theta generators. We propose a mechanism for segregating or integrating hippocampal computations based on the flexible coordination of different theta frameworks to accommodate the cognitive needs.

Keywords: cross-frequency coupling; gamma; hippocampus; information transmission; learning; neuroscience; rat; theta.

Plain language summary

In the brain, a vast number of neurons coordinate their activity to support complex cognitive processes. One of the best places to see this in action is the hippocampus, a brain structure with a key role in memory and navigation. The hippocampus shows waves of electrical activity, which represent the synchronized firing of large numbers of neurons. The hippocampus can generate multiple rhythms at once. The two main rhythms are theta and gamma. Theta waves are slow, with a frequency of about 8 Hertz. Gamma waves are faster with a frequency of up to 120 Hertz or even more. Theta waves are always present in the brains of freely moving animals, whereas gamma waves occur in brief bursts. These bursts usually correspond to a particular point on the theta wave. One burst may occur just before each peak of the theta wave, for example, whereas another burst may occur just after the peak. This separation enables individual bursts of gamma to carry different messages without them becoming mixed up. This is similar to how radio stations broadcast their signals at different carrier frequencies to avoid interference. By recording hippocampal activity in rats exploring a maze, Lopez-Madrona et al. now show that the hippocampus has not one, but three generators of theta waves. Having three sources of theta, each of which can be synchronized with gamma, provides a more versatile system for encoding and sending information. It also means that the three theta generators can vary the degree to which they coordinate their firing. This helps the brain combine or separate streams of information as required. By working together to create a single theta rhythm, for example, the three theta generators can help animals combine information stored in memory with incoming sensory input. How the coordination of theta rhythms in the hippocampus influences the activity of other brain regions involved in learning and memory remains unclear. However, uncoupling of theta and gamma waves seems to be an early sign of Alzheimer’s disease and can also be seen in the brains of people with schizophrenia and other psychiatric disorders. Understanding how this process occurs could provide clues to the origin of these disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Exploratory Behavior / physiology*
  • Hippocampus / physiology*
  • Male
  • Memory / physiology*
  • Rats
  • Rats, Long-Evans
  • Theta Rhythm / physiology*