title: Olfactory memory and maternal behaviour-induced changes in c-fos and zif/268 mRNA expression in the sheep brain.
abstract: In sheep maternal behaviour and the formation of the selective olfactory, ewe/lamb bond are induced by feedback to the brain from stimulation of the vagina and cervix during parturition. In the present study, we have used in situ hybridization histochemistry to quantify changes in cellular expression of two immediately-early genes, c-fos and zif/268, in order to identify activated brain regions during the induction of maternal behaviour and olfactory bonding as well as regions where plastic changes are occurring during with the formation of the olfactory memory associated with bonding. Three different treatment groups were used. One group gave birth normally, became maternal and were allowed to interact with their lambs for 30 min. A second group received exogenous treatment with oestradiol and progesterone to induce lactation and then received a 5-min period of artificial stimulation of the vagina and cervix (VCS) which reliably induces maternal behaviour but could not interact with lambs. A final control group received exogenous hormone treatment but no VCS or interaction with lambs. Compared to the control group, post-partum animals and animals that had received VCS showed increased c-fos expression in a number of cortical regions (cingulate, entorhinal and somatosensory), the mediodorsal thalamic nucleus and the lateral habenula, the limbic system (bed nucleus of the stria terminalis, lateral septum, medial arnygdala, dentate gyrus and the CA3 region of the hippocampus) and the hypothalamus (medial preoptic area, mediobasal hypothalamus, paraventricular nucleus, supraoptic nucleus and periventricular complex). The group that gave birth and had contact with their lambs for 30 min had significantly enhanced c-fos mRNA expression in the cingulate cortex compared to those receiving VCS and additionally showed significantly increased c-fos mRNA expression in olfactory processing regions (olfactory bulb, piriform cortex and orbitofrontal cortex). Expression of zif/268 was significantly increased in the entorhinal cortex, orbitofrontal cortex and dentate gyrus of the parturition group compared to either the control or the VCS alone groups. These results show a clear differentiation between neural substrates controlling the expression of maternal behaviour and those involved in the olfactory memory process associated with selective recognition of offspring although at the level of the hippocampus and cingulate cortex there may be some degree of overlap. Alterations in zif/268 at tertiary processing sites for olfactory information (orbitofrontal cortex) and the entorhinal cortex and dentate gyrus may reflect plastic changes occurring during the early stages of olfactory memory formation.
authors.affiliation: Department of Neurobiology, Babraham Institute, Cambridge, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Da Costa
authors.forename: K D
authors.initials: KD
authors.lastname: Broad
authors.forename: K M
authors.initials: KM
authors.lastname: Kendrick
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002584:Cervix Uteri / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D017781:Genes, Immediate-Early / Q000235:genetics*; D016762:Genes, fos / Q000235:genetics*; D017403:In Situ Hybridization; D007774:Lactation / Q000187:drug effects; D008425:Maternal Behavior / Q000502:physiology*; D008568:Memory / Q000502:physiology; D009769:Object Attachment; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D012756:Sheep / Q000502:physiology*; D012903:Smell / Q000502:physiology*; D014621:Vagina / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol