Circadian rhythm disruption -> too much GABA -> learning problem

Norman F. Ruby, Calvin E. Hwang, Colin Wessells, Fabian Fernandez, Pei Zhang, Robert Sapolsky, and H. Craig Heller. Hippocampal-dependent learning requires a functional circadian systemPNAS 2008 105:15593-15598; published ahead of print October 1, 2008, doi:10.1073/pnas.0808259105

The hamsters were first exposed to two hours of bright light late at night. Then the next day the researchers delayed the usual light/dark cycle by three hours.

This disrupted their circadian rhythm, and made it hard for them to learn.

Control hamsters exhibited normal circadian modulation of performance in a delayed novel-object recognition task. By contrast, arrhythmic animals could not discriminate a novel object from a familiar one only 20 or 60 min after training.

Memory performance was not related to prior sleep history as sleep manipulations had no effect on performance.

Because GABA is the primary neurotransmitter of the SCN, we hypothesized that the normal pattern of GABA output from the SCN may have been altered in arrhythmic hamsters in such a way as to increase inhibitory input at SCN target sites involved in cognition.

“What I thought was happening was that our animals were having chronically high levels of GABA because they had lost their circadian rhythm,” Ruby said. “So instead of rhythmic GABA, it is just constant GABA output.”
(from the press release (the first link))

So to test this, they blocked GABA, and indeed,

The GABA antagonist pentylenetetrazol restored learning without restoring circadian rhythms…

One interesting thing this is that it adds another item to the list of functions of the circadian rhythm, a list that is so far is surprisingly short:

…the good health and longevity of suprachiasmatic nucleus (SCN)-lesioned animals support the notion that the circadian system is of little consequence to their overall physiology. One notable exception to this trend is reproduction in rodents. Elimination of circadian timing by SCN ablation eliminates estrous cycles and thereby prevents reproduction… (from the journal article)


One thought on “Circadian rhythm disruption -> too much GABA -> learning problem

  1. I initiated morning light therapy a few years ago to treat a very severe circadian rhythm disorder (delayed sleep phase syndrome; confirmed in an overnight study at a sleep lab). My case was so extreme that I was at my best from midnight to 7 A.M. The light therapy worked beautifully! However, when I adopted a daytime schedule, I developed an equally severe sleepwalking problem. I was sleepwalking several times a week, sometimes sustaining injuries and/or breaking objects.

    I started taking GABA supplements at night as a treatment for mild anxiety. It didn’t work for the anxiety at all – but it unexpectedly “cured” my sleepwalking! I discontinued the GABA supplements at one point, thinking maybe I’d just “gotten over” the sleepwalking problem; I was sleepwalking again within a week. I now take the GABA supplements nightly. However, it definitely seems to cause memory problems. I don’t feel dopey or drugged after taking it, but I’ll watch an entire TV program or read a book chapter, and then I remember virtually none of it the next day. It’s as if the memories just don’t “stick.”

    I think it’s very likely that all of these things are related…especially given the evidence put forth on this web page. Maybe worthy of future research….


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