We. Cullinan et al., PATTERN AND TIME-COURSE OF IMMEDIATE-EARLY GENE-EXPRESSION IN RAT-BRAIN FOLLOWING ACUTE STRESS, Neuroscience, 64(2), 1995, pp. 477-505
The pattern and time course of brain activation in response to acute s
wim and restraint stress were examined in the rat by in situ hybridiza
tion using complementary RNA probes specific for transcripts encoding
the products of the immediate early genes c-fos, c-jun and zif/268. A
widespread pattern of c-fos messenger RNA expression was detected in r
esponse to these stressors; surprisingly, the expression patterns were
substantially similar following both swim and restraint stress. A dra
matic induction of c-fos messenger RNA was observed in numerous neo- a
nd allocortical regions, the lateral septal nucleus, the hypothalamic
paraventricular and dorsomedial nuclei, the anterior hypothalamic area
, the lateral portion of the retrochiasmatic area, the medial and cort
ical amygdaloid nuclei, the periaqueductal gray, and the locus coerule
us; however, a prominent induction of c-fos was also seen in numerous
additional subcortical and brainstem regions. Although not as widely e
xpressed in response to stress as c-fos, induction of zif/268 messenge
r RNA was also detected throughout many brain areas; these regions wer
e largely similar to those in which c-fos was induced, although in a n
umber of regions zif/268 was expressed in regions devoid of c-fos mess
enger RNA. Few brain areas showed increased expression of c-jun follow
ing stress; these regions also showed induction of c-fos and/or zif/26
8. The time courses of expression of all three immediate early genes w
ere similar, with peak levels observed at the 30 or 60 min time point,
and a markedly reduced signal evident at 120 min post-stress. However
, in a number of cases a delayed and/or prolonged induction was noted
that may be indicative of secondary neuronal activation. A number of r
ecent studies have attempted to define neural pathways which convey st
ress-related information to the hypothalamic-pituitary-adrenal axis. T
he present results reveal a widespread pattern of neuronal activation
in response to acute swim or restraint stress. These findings may aid
in the identification of stress-specific neural circuits and are thus
likely to have important implications for our understanding of neurona
l regulation of the stress response.