Aug 262010
 

Dear Readers,

The “hippocampal theta rhythm” is a specific type of electrical activity that can be observed in the hippocampus and other brain structures in numerous species of mammals including rodents, rabbits, dogs, cats, bats and marsupials.

In the oldest EEG literature dating back to the 1920s, Greek letters such as alpha, beta, theta and gamma were used to classify EEG waves falling into specific frequency ranges, with “theta” generally meaning a range of about 4–7 cycles per second (Hz).

In the 1930s–1950s, a very strong rhythmic oscillation pattern was discovered in the hippocampus of cats and rabbits. In rats, hippocampal theta is seen mainly in two conditions: first, when an animal is running, walking or in some other way actively interacting with its surroundings; second, during REM. The presence of theta in the hippocampal EEG can be predicted on the basis of what an animal is doing, rather than why the animal is doing it. Theta-frequency EEG activity is also manifested during some short-term memory tasks. Theta rhythms are very strong in rodent hippocampi during learning and memory retrieval, and are believed to be vital to the induction of long-term potentiation, a cellular mechanism of learning and memory.

In the August 18 Journal of Neuroscience, researchers led by Aline Stéphan at Paris Descartes University, France, report that Aß dampens the electrical theta oscillations of the rat hippocampus, and this modulation correlates with a decline in learning ability. This decline in theta is not due to cell death, but instead reflects a change in firing patterns. The findings point to another mechanism by which AD may disrupt normal cognitive functions, such as learning and memory.

Villette and colleagues assessed the memory of injected rats using a novel-object recognition test, a paradigm requiring intact hippocampal function. Rats were presented with a variety of objects every other day for three weeks, with one object always being the same. While rats injected only with placebo gradually spent less time exploring the familiar object and more time exploring the novel ones, Aß-injected rats showed the opposite tendency, an effect that grew worse two to three weeks after the injections. In other words, the ability of Aß-treated rats to distinguish between novel and familiar objects gradually declined.

Villette and colleagues also recorded electrical activity during object exploration, when theta oscillations are maximal in normal rats, and found that in the Aß-treated rats, the power of the theta frequencies decreased between days 9 and 21 after injections. In addition, when placebo-treated rats learned to discriminate between a novel and a familiar object, their peak theta frequency dropped from about 7.5 Hz to 7.1 Hz when exploring the novel object, an effect seen in other studies, but in Aß-treated rats, the theta frequency stayed constant at 7.6 Hz, correlating with a lack of learning.

This is an important paper for many reasons. First, it suggests that beta-amyloid is negatively impacting memory function even when the brain is still structurally intact (that is, no hippocampal atrophy has taken place). This form of beta-amyloid may be causing trouble before it has even deposited into plaques. More importantly, it opens up the possibility that by reinstating the theta frequency pharmacologically, we might have a new avenue to consider for early AD treatment.

Villette V, Poindessous-Jazat F, Simon A, Léna C, Roullot E, Bellessort B, Epelbaum J, Dutar P, Stéphan A. Decreased rhythmic GABAergic septal activity and memory-associated theta oscillations after hippocampal amyloid-beta pathology in the rat. J Neurosci. 2010 August 18;30(33):10,991-11,003.

Michael Rafii, M.D., Ph.D
Associate Medical Director, ADCS
This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

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