Remember to sleep; sleep to remember

by George Wilkinson

In the broadest sense, sleep is defined as a period of inactivity and loss of awareness. Most humans sleep 7–8 h per night, and if we are deprived of sleep, our cognitive performance, metabolism and health suffer. Sleep clearly contributes to several important physiological functions. Hypotheses for sleep benefits include overall rest and healing; cellular metabolism or replenishment; and brain-specific functions such as synaptic adjustments important for memory. Specifically, scientists believe our brains require sleep to process what we experienced during the day. However, the specific relationship between sleep hygiene and memory function remains controversial.

In recent years, seminal insights into the control and genetics of sleep have come from studies in flies, fish, and worms. Genetic screens have identified mutations that affect sleep across species, pointing to an evolutionarily conserved regulation of sleep. Moreover, a number of laboratories have identified sleep-dependent changes in gene expression, including in genes involved in learning and memory consolidation. A recent article in the open-access journal PLoS One explores the possible connection between memory and sleep in the regulation of one such gene, brain-type Fatty acid binding protein 7 (Fabp7), in sleep and long-term memory formation in flies.

The authors had earlier shown that Fabp7 is expressed in mice at different levels during the circadian rhythm. In this work, they found that in flies, too, the homologous gene is more highly expressed during sleep stages and less expressed after waking. To find out if Fabp7 expression affects sleep patterns, they generated transgenic flies overexpressing either the fly or the mouse version of Fabp7. Induction of either transgene to high levels resulted in a substantial net gain in daytime sleep relative to controls. To test whether misexpression of this protein and/or the accompanying sleep changes affect memory consolidation, they tested groups of flies in an olfactory avoidance test. Sustained overexpression over 2-7 days resulted in a 45% improvement in population learning of the transgenic flies relative to the control population. The improvement in olfactory avoidance was highly correlated with overexpression levels and with increased sleeping.

In their discussion, the authors caution that they do not know if their overexpression of this gene directly affects the long-term memory process in these flies, or if rather the increase in daytime sleep seen in overexpressors resulted in an indirect performance advantage in the test. Toward distinguishing these two, it would be very interesting to force overexpression of Fabp7 in flies with genetic disturbances of affecting sleep or memory in isolation. I think the promise of this type of approach is the genetic tractability of flies as well as the ability to make precise measurements on large numbers of creatures.