CROSS-SPECIES TRANSPLANTATION OF CIRCADIAN BEHAVIOR

The long term goal of this research is to furnish an understanding of the
complex neural substrates underlying the regulation of circadian behavior
by utilizing a cross-species neural transplantation model. Increased
knowledge of the functional organization of the hypothalamus and the
circadian timing system is relevant to problems of sleep, jet lag and
some kinds of serious affective disorders. The suprachiasmatic nucleus (SCN) of the anterior hypothalamus has been
identified as a circadian oscillator and as an integral component of the
endogenous biological timing system. However, the extent to which the
SCN functions as an autonomous pacemaker, determining the period of
expressed circadian behaviors, remains to be established. The specific
aim of this proposal is to transplant the SCN from one species into an
SCN-lesioned, arrhythmic host of a different species to determine whether
the restored circadian behavior exhibits the species-typical behavior of
the donor, the host, or a donor/host intermediate. The restoration of
donor-specific circadian behavior will firmly establish the autonomy of
SCN as a circadian pacemaker. The behavioral -marker assayed is the species-typical circadian period of
wheel-running activity. Upon establishing host base-line circadian
behavior, the host is rendered arrhythmic by lesioning the SCN. After
monitoring post-lesion behavior, the SCN from a fetal donor of a
different species is implanted into the lesion site of the host and
behavior is monitored to assay the period of the restored activity.
Behavioral analysis determines the functional capabilities of the graft.
Histochemical procedures will verify the absence of the host SCN and
immunocytochemical analysis at the light and electron microscopic level
with species-specific monoclonal antibodies and antibodies for SCN
peptides establish the extent of graft-host integration.