[Abstract Title]. - Society for Neuroscience

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 282.5/OO12
Topic: E.06.d. Cellular actions of stress
Title: Activation of locus coeruleus neurons projected from corticotropin-releasing factor
neurons in the hypothalamic paraventricular nucleus is involved in arousal response
accompanied by yawning behavior in rats
Authors: *N. KUBOTA, T. OTSUKA, S. YANAGITA, C. MOTOKI, I. KITA;
Tokyo Metropolitan Univ., Hachioji, Japan
Abstract: Our previous studies have showed that an arousal response accompanied by yawning
behavior can be evoked by electrical and chemical stimulation of the hypothalamic
paraventricular nucleus (PVN) in rats. Furthermore, we have suggested that activation of
corticotropin-releasing factor (CRF) neurons in the PVN is involved in a stereotyped yawning
response, which was characterized by a single large inspiration, an initial fall blood pressure
(BP), and an arousal shift in the electrocorticogram (ECoG), using c-Fos immunohistochemistry
in rats. Recently, we found that intracerebroventricular (icv) administration of CRF antagonist
attenuates arousal response accompanied by yawning behavior in rats. Although these findings
suggest that CRF neurons in the PVN are primarily responsible for the arousal response during
yawning, the CRF-containing pathway involved in the arousal response accompanied by
yawning evoked by the PVN stimulation is still unknown. CRF is known to serve as an
excitatory neurotransmitter in the locus coeruleus (LC), which is one of the neuronal aggregates
within the brainstem reticular formation responsible for cortical activation and one of the major
sources of noradrenalin (NA) in the central nervous system. Several neuroanatomical studies
have suggested that the LC receives CRF afferents from PVN, and projects to various brain areas
including regions of cortex. Therefore, it is possible that activation of the noradrenergic system
by the PVN CRF neurons projecting to the LC is responsible for the arousal response during
yawning induced by PVN stimulation. In the present study, we examined the involvement of LC
neurons projected from PVN CRF neurons in the arousal response during yawning with doublestaining
for c-Fos and CRF in the PVN, and for c-Fos and NA in the LC after CRF antagonist
(icv) in anesthetized, spontaneously breathing rats. In addition, we also recorded the ECoG to
evaluate the effect of CRF antagonist on arousal responses during yawning. Microinjection of Lglutamate
into the PVN induced a frequent yawning accompanied by an arousal shift in the
ECoG even after CRF antagonist (icv), but the arousal response was significantly suppressed
compared to that after saline (icv). The effect of CRF antagonist (icv) on arousal response during
yawning was associated with c-Fos expression in the LC, and with activation of the CRF neurons
in the PVN. These results suggest that the arousal response accompanied by yawning behavior
might be mediated by LC neurons projected from PVN CRF neurons.
Disclosures: N. Kubota, None; T. Otsuka, None; S. Yanagita, None; C. Motoki, None; I.
Kita, None.