Professor Hugh Piggins (BSc, PhD) - research

Appetite and Body Weight Regulation, Chronobiology, Neurophysiology

Neuropeptides and behaviour

My laboratory is interested in the role played by neuropeptides in the neural mechanisms underlying the synchronisation of behaviour with cyclical variation in the environment. It has been established that a structure in the mammalian hypothalamus, the suprachiasmatic nucleus (SCN), contains a clock which generates near 24 hour (ie, circadian) rhythmic variations in both physiology and behaviour. This clock is synchronized (entrained) to changes in environmental illumination (ie, day/night variations) by photic information, which is conveyed directly to the SCN by retinal afferents to the hypothalamus, and indirectly via the lateral geniculate complex. Hence, daily variations in physiology and behaviour are the product of the entrainment of the circadian clock located in the SCN with the environment. The SCN contain a large number of neuropeptides, which are present in various neuronal elements- fibres, terminals, and cell bodies- and distributed in distinguishable patterns in this structure. Evidence suggests that certain neuropeptides may have an important role in circadian rhythms. For example, neuropeptide Y (NPY), which is believed to be the main neurotransmitter of geniculate afferents to the SCN, phase-shifts hamster locomotor activity rhythms when microinjected into the SCN region. In our research programme, we use a number of neuroscience techniques to investigate the peptidergic organization of the SCN, the responses of SCN cells to these peptidergic neuromodulators, and the effect of injecting these peptides into the SCN region on the circadian architecture of behaviour.

The lab's research programme is best illustrated by work we have done with the neuropeptide, gastrin-releasing peptide (GRP). We have developed an in vitro preparation in which the SCN clock can be maintained for up to 72h. We have found that GRP primarily activates rodent SCN neurones and phase-dependently phase-shifts the electrical activity rhythm of SCN cells. Microinjections of GRP into the SCN region in vivo reset rodent activity rhythms in a manner resembling the effects of light on behavioural rhythms. Further, GRP microinjections also induce the expression of the immediate early gene c-fos in the SCN region. Since GRP mimics the effects of light on the SCN clock and because glutamate is believed to be the principal neurotransmitter released from retinal afferent terminals in the SCN, we are currently examining the interaction between these neurochemicals in the determination of the phase of the SCN clock.

More recently, we have begun studying the roles played by VIP and VIP-related peptides in the SCN clock. These studies utilise transgenic knockout mice lacking different classes of VIP receptors to determine how these receptors might contribute circadian rhythm processes. The overall aim of this research is to determine the neurochemical events underlying the synchronisation of the SCN clock with the environment.