[3] In the lab of Colin Pittendrigh,[4][5] the father of research on biological clocks, Menaker studied the endogenous circadian rhythm of bats (Myotis lucifugus).
[7] When Menaker joined faculty at University of Texas at Austin in 1962,[4] he transitioned to studying circadian rhythms in the house sparrow (Passer domesticus)[8] and the golden hamster (Mesocricetus auratus).
[5] In 1968, Menaker provided evidence for the existence of extra-retinal photoreceptors that were sufficient for photoentrainment by measuring rhythmic locomotor behavior as the output signal of the house sparrows (Passer domesticus) circadian clock.
He demonstrated that photoentrainment could occur in the absence of optic neurons, evidence for the presence of an extra-retinal photoreceptor(s) coupled to the House Sparrow circadian clock.
He tested three possible confounding variables for entrainment: (1) temperature fluctuation, (2) post-enucleation retinal fragments remaining in the eye, and (3) ectoparasites that might transfer light information through their movements in the birds' skin.
To study the effects of temperature on circadian rhythms, Menaker exposed the enucleated sparrows to an electroluminescent panel.
Menaker treated sparrows with Dry-Die, an anti-parasitic agent, to eliminate any possible effects of light transferring by ectoparasites.
These results demonstrate that retinal light receptors are not necessary for photoentrainment, indicating there is an extra-retinal photoreceptor(s) contributing to circadian locomotor activity.
Menaker's findings in enucleated sparrows were consistent with Aschoff's Rule, and he concluded that the retinae and the extra-retinal receptor(s) both contribute to the photoentrainment process.
In 1988, Martin Ralph and Menaker serendipitously came across a tau mutant male golden hamster in a shipment from their commercial supplier, Charles River Laboratories, that was observed to have a circadian period significantly shorter than what is characteristic of that breed.
[15] That same year, Gianluca Tosini and Menaker also determined that hamster retinas cultured in vitro produced a consistent circadian rhythm, as measured by melatonin levels.
[17] GDRDA works by first generating polymorphic genetic markers for a monogenic trait (which the tau has already been proven to be) that can be directly identified in the genome.
This hypothesis states that the spontaneous consumption of MAP in drinking water by rodents results in lengthened bouts of activity, followed by sleep.
[20] Menaker and colleagues investigated if MASCO affected the molecular feedback loop underlying the currently accepted model for circadian rhythmicity in mammals.
All of these mutants continued to respond and exhibit changes in free-running rhythms in the presence of MAP, despite mutational breaks in the feedback loop for circadian oscillation.
In these arrhythmic animals, regardless of mutation or knockout of critical clock genes, MAP restored rhythm of circadian properties.
Menaker discovered another mutant hamster, this time showing a free-running period of 25 hours in conditions of constant darkness.