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Query: UNIPROT:Q86TM3 (cage)
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Intense depolarizing stimuli induce the expression of the proto-oncogene c-fos which may be useful as a marker of neuronal activity. To determine if mild physical and behavioral stressors may also induce c-fos expression, we subjected rats to an unconditioned stressor (footshock) or a conditioned stressor (a tone previously paired with footshock) and measured c-fos mRNA levels in various brain regions using in situ hybridization. Removing rats from their home cage and exposing them to a tone was sufficient to cause increases in c-fos mRNA in several forebrain areas while further increases in c-fos occurred in the septum, cingulate cortex, and endopiriform nucleus in response to acute footshock stress. Both unconditioned and conditioned stressors increased c-fos mRNA levels in the locus ceruleus which correlated with stress-induced plasma corticosterone concentrations. Unconditioned footshock stress also increased c-fos mRNA in the hypothalamic paraventricular nucleus (PVN). However, neither conditioned nor unconditioned stressors induced c-fos in the PVN in rats which had been previously exposed to footshock. C-fos appears to be a sensitive marker for stress-responsive brain areas and may be important in mediating long-term neurochemical changes that result from stress.
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PMID:Induction of c-fos mRNA in rat brain by conditioned and unconditioned stressors. 151 Dec 71

Levels of c-fos mRNA were measured with in situ hybridization to test for behaviorally dependent changes in neuronal activity in three subdivisions of hippocampus and in components of the olfactory and visual systems. In rats that performed a well-learned nose-poke response for water reward, c-fos mRNA levels were broadly increased, relative to values in home cage-control rats, in visual cortex, superior colliculus, olfactory bulb, and, to comparable levels, regions CA3 and CA1 of hippocampus; hybridization was not increased in the dentate gyrus. In rats first trained on the nose-poke behavior and then required to discriminate between two odors for water reward, the increase in c-fos mRNA was generally not as great and was more regionally differentiated. Thus, in olfactory bulb, hybridization was more greatly elevated in lateral than medial fields, thereby exhibiting regional activation corresponding to the topographic representation of the predominant odor sampled in the discrimination task. In hippocampus of odor-discrimination rats, c-fos mRNA levels were far greater in the region CA3 than region CA1, but remained at cage control values in stratum granulosum. Interestingly, c-fos mRNA levels in each hippocampal subdivision were highly correlated with levels in other regions (e.g., visual cortex) for home cage controls but not for rats in the two behavioral groups. Thus, c-fos mRNA levels in cage-control rats appeared to be regulated by some generalized factor acting throughout much of the brain (e.g., arousal), while odor-discrimination performance changed the pattern of expression within hippocampus, and allowed for a differentiated response by olfactory regions to emerge. These findings suggest that hippocampus possesses multiple modes of functioning and makes contributions to behavior that vary according to task demands.
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PMID:Changes in c-fos mRNA expression in rat brain during odor discrimination learning: differential involvement of hippocampal subfields CA1 and CA3. 762 10

To discern the effects of hyperthermia on working memory, we recorded the ability of rats to discriminate between objects following microwave radiation exposure. Memory changes were evaluated by measuring relative exploration time of a familiar vs. a new stimulus object. A subject that extensively reexplores a stimulus with which it has previous experience is presumed to exhibit memory loss associated with that object. Between training and testing, rats were exposed to various doses of microwave radiation, were sham irradiated, or remained in their home cage. Brain (dural) and rectal temperatures were recorded. To discern brain regions activated or possibly damaged by microwave exposure, we also used immunocytochemistry techniques to identify sites of c-fos protein expression in the brains of several irradiated/sham-irradiated subjects. Rats exposed to > 5 W/kg exhibited hyperthermia when compared to nonirradiated controls. Normothermic control subjects (sham-irradiated rats and rats exposed to 0.1 W/kg) showed a distinct preference for the new object although other microwave-exposed rats (1, 5, 8.5, 9.3, 10 W/kg) did not. Microwave hyperthermia evoked prominent c-fos expression in periventricular strata, hypothalamic nuclei, amygdala, and several areas of the cortex. These data suggest that performance on a putative working memory task may be disrupted by a sufficiently intense microwave-induced hyperthermia. The pattern of expression of the early proto-oncogene c-fos may suggest candidate brain nuclei that mediate the behavioral changes we observed.
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PMID:Disruption of a putative working memory task and selective expression of brain c-fos following microwave-induced hyperthermia. 804 68

The vomeronasal system projects to the accessory olfactory bulb (AOB), to the medial (Me) and posterior medial cortical nuclei (PMCN) of the amygdala, to the bed nucleus of the stria terminalis (BNST), and to other central structures shown to be important in mating behavior, including the medial preoptic area (MPOA). In these experiments c-fos expression was used as a marker of neural activity to identify the contribution of vomeronasal sensory input during mating behavior in male golden hamsters, either intact or with vomeronasal organs removed (VNX). Inexperienced hamsters were either stimulated with a receptive female and allowed to mate, exposed to female hamster vaginal fluid (HVF), which contains stimuli known to act through the VN system, or placed in a clean cage alone. Densely stained Fos-positive nuclei were evident in mated animals in the central VN pathway [AOB, Me, posterior medial BNST (pmBNST)] and a VN target area (MPOA). HVF-exposed animals showed Fos expression in the AOB, Me, and BNST but not MPOA. Unstimulated animals showed almost no activation. Most VNX animals exposed to females did not mate, but performed intense chemoinvestigation. They had few Fos-positive nuclei in any of these areas except the caudal pmBNST. A few VNX animals that did mate had patterns of Fos activation that were similar but less intense than those of intact mating animals, suggesting a selective activation of VN central pathways during mating regardless of VN sensory input. The main olfactory system showed low levels of Fos expression in all animals (stimulated and unstimulated). Fos expression in the MPOA and rostral pmBNST was seen only in mated animals, suggesting that these regions are concerned with mating performance or its consequences, rather than the chemosensory input that triggers it. Fos expression in the caudal encapsulated pmBNST was evident in all groups of animals that performed chemosensory investigation, regardless of VN status or mating, suggesting that this region either directs or responds to chemosensory investigation.
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PMID:c-fos expression in vomeronasal pathways of mated or pheromone-stimulated male golden hamsters: contributions from vomeronasal sensory input and expression related to mating performance. 820 79

To determine the cell groups which are activated by novelty stress, we examined the induction of c-fos mRNA in brain tissues following introduction of male rats to a novel open field. Male Fischer 344 rats were placed in a brightly lit open field and allowed to roam free for 20 min. Control animals were sacrificed upon removal from their home cage. Northern blot analysis revealed a 2.2 kb hybridization signal which increased in density following novelty. In situ hybridization analysis showed that c-fos mRNA was induced in a specific pattern consistent with the behavior. The regions of induction included the medial prefrontal and orbital cortex, cingulate and parietal cortex, hippocampal CA1 and CA3 pyramidal cell regions, dorsal and ventral anterior thalamic n. and paraventricular n. of the hypothalamus. C-fos mRNA also increased in the anterior pituitary gland and this increase correlated with the secretion of ACTH. These data demonstrate the brain areas undergoing genomic activation following complex behavior paradigms such as introduction to a novel environment.
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PMID:Induction of c-fos mRNA in the brain and anterior pituitary gland by a novel environment. 821 31

The two-process model of sleep regulation posits that a homeostatic drive to sleep, referred to as Process S, increases with time spent awake. The purpose of this study was to evaluate whether immediate early gene (IEG) expression increases in the brain in proportion to time spent awake, when Process S would be expected to increase. Rats were deprived of sleep by cage tapping, cage rotation and gentle handling beginning at light onset for 45 minutes, 3 hours or 6 hours. At the end of the deprivation periods, deprived animals and an equal number of controls were decapitated, the brains dissected into subregions and frozen. Northern blots were prepared from cortex, thalamus, cerebellum, pons and hypothalamus and hybridized with cDNA probes to five IEG mRNAs; c-fos, c-jun, junB, NGFI-A and NGFI-B. Basal levels of c-fos mRNA were detectable in all brain regions from all animals. Sleep-deprived animals showed higher expression of c-fos mRNA than control animals following 45 minutes and 6 hours of sleep deprivation in all brain regions examined, with the greatest increases observed in the cerebellum. Surprisingly, only the pons and cerebellum showed clear increases at the 3-hour timepoint. In contrast to c-fos, c-jun mRNA was essentially invariant among the animals while junB mRNA was inconsistently elevated. The expression of NGFI-A and NGFI-B was similar to the c-fos pattern but of lesser magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immediate early gene expression in brain during sleep deprivation: preliminary observations. 845 28

Expression of the immediate-early gene c-fos was used to evaluate the coordinate activation of olfactory bulb neurons by brief exposure to specific odors in the alert rat. In situ hybridization to c-fos mRNA was compared to regional increases in 2-deoxy-D-[14C]glucose incorporation in an adjacent section analysis. Levels of c-fos mRNA in olfactory bulb were high in rats recently removed from their home cage but were low in animals placed in a relatively odor-free chamber for 30 min. Presentation of specific odors to alert rats for as little as 5 min increased c-fos mRNA in radially distributed neuronal ensembles that spanned the lamina of the main olfactory bulb. The complementary RNA (cRNA)-labeled neuronal collectives consisted of cells in the glomerular layer that precisely defined the borders of individual glomeruli and underlying tufted, mitral, and granule cells. The activated fields were much broader in the granule cell layer than in the overlying glomerular layer and thus exhibited a flask-like, as opposed to a columnar, contour. The bulbar distribution of cRNA-labeled cell arrays differed with different odors and, in the glomerular layer, corresponded to focal regions of high 2-deoxy-D-[14C]glucose uptake. Administration of the noncompetitive N-methyl-D-aspartate receptor antagonist MK801 did not attenuate the odor induction of c-fos but, instead, increased c-fos mRNA levels throughout the bulb. We propose that the neuronal ensembles expressing increased c-fos mRNA with odor stimulation represent principal functional units of sensory processing in the main olfactory bulb of the behaving rat.
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PMID:Odor-induced increases in c-fos mRNA expression reveal an anatomical "unit" for odor processing in olfactory bulb. 847 76

The mating-induced preovulatory surge of luteinizing hormone (LH) lasts for at least 12 h in the female ferret. This prolonged increase in circulating LH is presumably accompanied by a corresponding elevation in the activity and output of luteinizing hormone-releasing hormone (LHRH) neurons projecting to the hypothalamic-hypophyseal portal blood vessels and adenohypophysis. We used the protein products of the immediate early genes (IEGs) c-fos, and c-jun as markers of neural activation in order to determine whether a sub-population of LHRH neurons is differentially activated by mating and whether non-LHRH neurons in specific forebrain regions are selectively activated at different times during the mating-induced preovulatory LH surge. In Experiment 1, estrous female ferrets were perfused 0.5, 1.5, 3.0, 6.0 or 12.0 h after receiving one 5-min intromission from a male or after being placed alone in a testing cage for 20 min. Fos-like immunoreactivity (Fos-IR; Oncogene Ab-2 antiserum) and LHRH-like immunoreactivity (LHRH-IR; LR-1 antiserum) were visualized. The percentage of Fos-IR LHRH neurons was significantly augmented 1.5 h after mating but had returned to basal levels by 3.0 h. The double-labeled LHRH neurons were concentrated in the caudal medio-basal hypothalamus. In non-LHRH neurons the number of Fos-IR neural nuclei was significantly increased by mating in the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BNST), medial amygdala (MA), ventrolateral hypothalamus (VLH), and midbrain central tegmental field (CTF) 1.5 h after mating but, as in LHRH neurons, had returned to basal levels by 3.0 h. In Experiment 2, estrous females were perfused 1.5 h or 8.0 h after either receiving one 5-min intromission or being placed alone in a testing cage, and the brains were processed for LHRH and c-Fos-like (DCH-1, Dr Gerard Evan), c-Jun-like (Jun-IR; Oncogene Ab-2) or Egr-1-like (Egr-IR; Santa Cruz) immunoreactivity. The percentage of LHRH neurons colabeled with both Fos-IR and Jun-IR was significantly greater in the 1.5 h group than in the unpaired group. Again, the induction of these IEG products occurred in LHRH neurons in the caudal medio-basal hypothalamus. Mating significantly increased the number of Fos-IR non-LHRH neural nuclei in the MPOA, BNST, MA, VMH and CTF, as well as the number of Egr-IR nuclei in the MPOA, BNST and MA in the 1.5 h group. By contrast, the number of Jun-IR non-LHRH neurons was unaffected by mating. In these Experiments we have identified a sub-population of LHRH neurons which, using Fos and Jun as markers of neural activation, is activated by mating and may be differentially involved in the generation of the preovulatory LH surge. Although the LHRH system is presumably activated throughout the duration of the 12 h preovulatory LH surge, c-Fos and c-Jun immunoreactivity in LHRH neurons is augmented only transiently. Fos-IR and Egr-IR in non-LHRH neurons show a similar time-course. Together, these results suggest that the presence of augmented levels of these proteins is not required for the maintenance or termination of the preovulatory output of LHRH.
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PMID:The temporal pattern of mating-induced immediate-early gene product immunoreactivity in LHRH and non-LHRH neurons of the estrous ferret forebrain. 873 34

The present study examined fetal alcohol effects (FAE) on the induction of the immediate early genes (IEGs) c-fos, jun B, c-jun, and zif268 mRNAs in the prefrontal cortex, hippocampus, and other brain regions after testing in an alternation task. Subjects were female offspring of Sprague-Dawley rats fed either a 35% ethanol-derived calorie diet, pair-fed with sucrose, or control-fed with laboratory chow during the last week of gestation. At 75-85 days of age, rats were food-deprived and trained in a t-maze for food reward. Then rats were tested at 5-sec, 30-sec, or 60-sec delays on each of 6 days. On the day of killing, a subset of rats was tested at the 60-sec delay for 12 trials and killed 30 min after testing. The remaining animals were killed from their home cage and acted as controls. Expression of the four IEG mRNAs was examined in the brains of these animals using in situ hybridization. FAE rats showed a memory deficit at the 60-sec delay (p < 0.05), but not at the 0-sec or 30-sec delays. Testing in the alternation task induced a significant elevation of c-fos, c-jun, jun B, and zif268 mRNA expression in the prefrontal cortex, hippocampal subfields CA1 and CA3, and several cortical areas. However, FAE rats showed a significantly smaller elevation of both c-fos and jun B mRNA levels in the orbital, prelimbic, and anterior cingulate regions of the prefrontal cortex (p < 0.05). FAE animals also showed a lower expression of jun B mRNA in the caudate nucleus. Significant correlations between the mean performance at the 60-sec delay and mRNA expression of c-fos, jun B, and zif268 in the prefrontal cortical regions (p < 0.05) were observed. These findings suggest that fetal alcohol exposure produces changes in the adult prefrontal cortex that may contribute to the behavioral deficit in the alternation task.
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PMID:Fetal alcohol exposure alters the induction of immediate early gene mRNA in the rat prefrontal cortex after an alternation task. 874

In female rats, vaginocervical stimulation induces neuroendocrine responses necessary for pregnancy as well as analgesia to a variety of noxious stimuli. In this study, Fos immunocytochemistry was used to detect vaginocervical stimulation-induced changes in the activity of spinal neurons at levels T11-S3, segments known to receive afferent input from nerves which innervate the reproductive tract. Adult ovariectomized estrogen and progesterone-treated rats were killed 1 h after receiving mating stimulation from males, which included five or 15 intromissions, mounts-without-intromission by use of either vaginal masks or genitally-anaesthetized males, or immediately after being removed from their home cages. At all spinal levels, Fos labelling was lowest in the home cage group (50 +/- 22 cells), intermediate in the groups receiving intromissions (84 +/- 8 and 118 +/- 22 cells) and highest in groups receiving mounts-without-intromission stimulation (187 +/- 21 and 218 +/- 35 cells). Significant increases above control levels following intromissive stimulation were observed at levels L6, S1 and S2. Surprisingly, both groups receiving mounts-without-intromission showed significantly higher numbers of Fos-positive cells than did the fully mated groups at all levels. Analysis of selected spinal segments by Rexed's laminae revealed that intromissive stimulation increased Fos labelling above control levels in laminae II-V and X at L6, and laminae I, II, V and X at S1; vaginocervical stimulation did not increase labelling at L1. The greater Fos responses seen in mounts-without-intromission animals than in control or intromitted animals were apparent at L1, L6 and S1 within the same laminae (II-V and X). These results suggest that stimulation of the uterine cervix initiates activity within L6-S2 neurons which receive pelvic nerve afferents and that such stimulation suppresses activity at all levels within populations of neurons normally activated by cutaneous somatic inputs received from male mounts. As antinociceptive agents are known to suppress c-fos expression, vaginocervical stimulation received during natural mating may be capable of initiating spinal and/or brain mechanisms of analgesia.
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PMID:Vaginocervical stimulation suppresses the expression of c-fos induced by mating in thoracic, lumbar and sacral segments of the female rat. 884 89


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