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The Structure and Function of the Endocrine Hypothalamus
The neuroendocrine cells in the hypothalamus control all reproductive and homeostatic mechanisms. We are presently studying how the suprachiasmatic nucleus of the hypothalamus ("the biological clock") and its inputs from elsewhere in the brain impose a daily rhythm of activity on a number of different hypothalamic secretory nuclei, notably the supraoptic, the paraventricular and the arcuate nuclei. Information is carried from the suprachiasmatic nucleus to the secretory nuclei by spike activity in the intervening nerve fibres. Since all spikes have the same amplitude, the coding is carried by the intervals between the spikes and recent work has made it possible to start to decode the patterns of spike activity. We also studying how other agents eg melatonin, leptin and gonadal steroids which modify the rhythms of activity seen in the different nuclei controlled by the SCN exert their action and modify the behaviour of neurotransmitter agents such as glutamate and gamma amino butyric acid. We use mainly electrophysiological methods (extracellular recording in vivo and in vitro, whole cell patch recording in vitro) and have developed a method for measuring neural activity based on the analysis of the intervals between spikes (see Bhumbra and Dyball, J Physiol, 555, 281-296; Bhumbra et al J Physiol, 563, 292-307).
We normally use two measures of spike coding in addition to mean spike frequency. The entropy of the probability distribution of the log inter-spike intervals quantifies their variability, and the mutual information between adjacent log inter-spike intervals measures the extent of the occurrence of spike motifs. By musical analogy, if the frequency provides the key of the scale, the log interval entropy quantifies the timbre of the notes that can be played by a particular musical instrument, and the mutual information quantifies the ordering of notes that constitute a tune. Frequency, entropy, and mutual information all convey different information and can vary independently since one cannot be inferred simply from another (see Bhumbra and Dyball, 2004, Bhumbra and Dyball 2005). A tune sounds different when played on a different musical instrument but may be readily recognised regardless of the key in which it is played
LabSpike: The software used in for the discrimination of spikes from noise in recent papers can be downloaded here.
Dr S Lombardelli
Dr K Saeb-Parsy
Dr G S Bhumbra
Prof AN Inyushkin
Dr JA Gonzalez
Saeb-Parsy K, Lombardelli S, Khan FZ, McDowall K, Au-Yong ITH & Dyball REJ (2000) Neural connections of hypothalamic neuroendocrine nuclei in the rat. J Neuroendocrinol. 12, 635-648.
Dyball REJ and McKenzie DN (2000) Synchronised Clusters of action potentials can increase or decrease the excitability of the axons of magnocellular hypothalamic neurosecretory cells. J Neuroendocrinol. 12, 729-735
Saeb-Parsy K. & Dyball R.E.J. (2001) What really happens in the SCN at night. J. Physiol 532, 1
H. Yamashita, Y Ueta and REJ Dyball (2002) Electrophysiological and molecular properties of oxytocin and vasopressin secreting systems in mammals. In: Hormones, Brain and Behaviour Ed DW Pfaff, APArnold, AM Etgen, SE Fahrbach, RL Moss and RR Rubin. Academic Press.
K. Saeb-Parsy and R. E. J. Dyball (2003) Defined Cell Groups in the Rat Suprachiasmatic Nucleus Have Different Day/Night Rhythms of Single-Unit Activity In Vivo. Journal of Biological Rhythms, 18, 26-4
K. Saeb-Parsy and R. E. J. Dyball (2003) Responses of cells in the rat suprachiasmatic nucleus in vivo to stimulation of afferent pathways are different at different times of the light/dark cycle. Journal of Neuroendocrinology, 15, 895-903.
K. Saeb-Parsy and R. E. J. Dyball (2004) Responses of cells in the rat supraoptic nucleus in vivo to stimulation of afferent pathways are different at different times of the light/dark cycle Journal of Neuroendocrinology 16, 131-137 (pdf)
G. S. Bhumbra and R. E. J. Dyball (2004) Measuring Spike Coding in the Supraoptic Nucleus J Physiol, 555, 281-296. (pdf)
G. S. Bhumbra, A. N. Inyushkin and R. E. J. Dyball (2004) Assessment of spike activity in the Supraoptic nucleus. Journal of Neuroendocrinology 16, 390-397 (pdf)
G.S. Bhumbra, A. N. Inyushkin, K. Saeb-Parsy, A. Hon and Dyball REJ (2005) Rhythmic changes in spike coding in the rat suprachiasmatic nucleus. J Physiol, 563, 292-307 (pdf)
G. S. Bhumbra, A. N. Inyushkin, M. Syrimi, R. E. J. Dyball (2005) Spike Coding during Osmotic Stimulation of the Rat Supraoptic Nucleus. J Physiol. 569, 257-274 (pdf)
Gonzalez J. A. and Dyball R. E. J. (2006) Pinealectomy reduces optic nerve but not intergeniculate leaflet input to the suprachiasmatic nucleus at night. Journal of Neuroendocrinology. 18, 146-153 (pdf)
Patrick N. Pallier, Elizabeth S. Maywood, Zhiguang Zheng, Johanna E. Chesham, Alexey N. Inyushkin, Richard Dyball, Michael H. Hastings and A. Jennifer Morton. (2007) Pharmacological imposition of sleep slows cognitive decline and reverses dysregulation of circadian gene expression in a transgenic mouse model of Huntington's disease. Journal of Neuroscience 27, 7869-7878.
A. N. Inyushkin, G. S. Bhumbra, J. A. Gonzalez, R. E. J. Dyball (2007) Melatonin modulates spike coding in the rat suprachiasmatic nucleus. Journal of Neuroendocrinology 19, 671-681
G. S. Bhumbra, H. O. Orlans and R. E. J. Dyball (2008) Osmotic modulation of stimulus-evoked responses in the rat supraoptic nucleus. European Journal of Neuroscience, 27, 1989-1998.
Above: Images of some stages involved in the analysis of the interval patterns seen in spontaneous firing.
Three dimensional representations of phase interval histograms showing responses to low (above) and high (below) intensity stimuli.