Biological Timing:


What makes you tick?
What is the role of Neuropeptide Y in circadian clock function?
The SCN receives photic input from the retina via a direct monosynaptic projection from the retina to the SCN known as the retinohypothalamic tract (RHT). This pathway is thought to utilize glutamate as its primary transmitter to transmit photic information to the SCN. A second indirect pathway to the SCN arises from the intergeniculate leaflet (IGL) of the lateral geniculate nucleus (LGN) and utilizes neuropeptide Y (NPY) as a transmitter. Although glutamate is thought to be the primary transmitter signalling photic information to the SCN, it is likely that NPY modulates the effect of glutamate on the pacemaker.
This is because:
1. Alterations in the pattern of entrainment can be seen after lesions of the IGL.
2. NPY containing fibres from the IGL project to the ventrolateral portion of the SCN which is innervated by the RHT.
3. Neurones activated by stimulation stimulation of the RHT are more likely to respond to application of NPY than those not activated.
4. NPY has been shown to modulate the effect of light pulses in behavioural experiments.
5. Finally NPY alters phase shifts to glutamate in the hypothalamic slice preparation.
This series of experiments which monitors clock output both in vivo and in vitro will provide a comprehensive examination of the mechanism by which NPY influences entrainment, from activity at the single cell level through to neuronal activity rhythms and behaviour. With these experiments we will begin to explore the mechanism by which NPY effects phase shifts to light. We will do this by (1) examining how disruptions or enhancement of NPY activity alter the responses of SCN neurones to glutamate or optic nerve stimulation (2) determining how disruptions or enhancement of NPY activity effects phase shifts to light.
People on the Project:  Gurprit Lall & Ron Blance
        Funding:

        Funding to support this work comes from the Biotechnology and Biological Sciences Research Council, and the
        Scottish Hospital Endowment Research Trust.

 
Related references:

Lall G. & Biello S.M. “Neuropeptide Y, GABA and circadian phase shifts to photic stimuli.” Neuroscience (2003) 120, 915-921.

Lall G. & Biello S.M. “Light induced phase advances and delays in the circadian rhythm of hamsters are
attenuated by neuropeptide y and [leu31, pro34]npy.” Neuroscience (2003) 119, 625-631.

Lall G. & Biello S.M.  “Attenuation of phase shifts to light by activity or neuropeptide y: a time course study.” Brain Research (2002) 957 p109-116.

Biello, S.M., Golombek, D.A., Schak, K.M. and Harrington, M.E., "Circadian phase shifts to neuropeptide y in vitro : Cellular communication and signal transduction." J.Neuroscience, 17 (1997) 8468-8475.

Biello, S.M., Golombek, D.A. and Harrington, M.E., "Neuropeptide Y and glutamate block phase shifts in the suprachiasmatic nucleus in vitro." Neuroscience, 77 (1997) 1049-1058.