Expression Of Fos-like Protein Research Articles

C57BL/6J offspring mice reared by a single-mother exhibit, compared to mice reared in a biparental parenting structure, distinct neural activation patterns and heightened ethanol-induced anxiolysis.

Parenting experiences with caregivers play a key role in neurodevelopment. We recently reported that adolescents reared by a single-mother (SM) display an anxiety-prone phenotype and drink more alcohol, compared to peers derived from a biparental (BP) rearing condition. To investigate if SM and BP offspring infant mice exhibit differential sensitivity to ethanol-induced locomotor activity and differential activity patterns in brain areas related to anxiety response. We also analyzed anxiety response and ethanol-induced anxiolysis in SM and BP adolescents. Mice reared in SM or BP conditions were assessed for (a) ethanol-induced locomotor activity at infancy, (b) central expression of Fos-like proteins (likely represented mostly by FosB, a transcription factor that accumulates after chronic stimuli exposure and serves as a molecular marker of neural plasticity) and cathecolaminergic activity, and (c) anxiety-like behavior and ethanol-induced anxiolysis in adolescence. Infant mice were sensitive to the stimulating effects of 2.0g/kg alcohol, regardless parenting structure. SM mice exhibited, relative to BP mice, a significantly greater number of Fos-like positive cells in the central amygdala and basolateral amygdala nuclei. Ethanol treatment, but not parenting condition, induced greater activation of dopaminergic neurons in ventral tegmental area. SM, but not BP, adolescent mice were sensitive to ethanol-induced anxiolysis. These results highlight the complex relationship between parenting experiences and neurodevelopment. The SM parenting may result in greater neural activation patterns in brain areas associated with anxiety response, potentially contributing to increased basal anxiety and alcohol sensitivity.

Loss of dexras1 Alters Nonphotic Circadian Phase Shifts and Reveals a Role for the Intergeniculate Leaflet (IGL) in Gene-Targeted Mice

Loss of Dexras1 in gene-targeted mice impairs circadian entrainment to light cycles and produces complex changes to phase-dependent resetting responses (phase shifts) to light. The authors now describe greatly enhanced and phase-specific nonphotic responses induced by arousal in dexras1−/− mice. In constant conditions, mutant mice exhibited significant arousal-induced phase shifts throughout the subjective day. Unusual phase advances in the late subjective night were also produced when arousal has little effect in mice. Bilateral lesions of the intergeniculate leaflet (IGL) completely eliminated both the nonphotic as well as the light-induced phase shifts of circadian locomotor rhythms during the subjective day, but had no effect on nighttime phase shifts. The expression of FOS-like protein in the suprachiasmatic nucleus (SCN) was not affected by either photic or nonphotic stimulation in the subjective day in either genotype. Therefore, the loss of Dexras1 (1) enhances nonphotic phase shifts in a phase-dependent manner, and (2) demonstrates that the IGL in mice is a primary mediator of circadian phase-resetting responses to both photic and nonphotic events during the subjective day, but plays a different functional role in the subjective night. Furthermore, (3) the change in FOS level does not appear to be a critical step in the entrainment pathways for either light or arousal during the subjective day. The cumulative evidence suggests that Dexras1 regulates multiple photic and nonphotic signal-transduction pathways, thereby playing an essential role modulating species-specific characteristics of circadian entrainment. (Author correspondence: ralph@psych.utoronto.ca)

Differential effects of stress and amphetamine administration on Fos‐like protein expression in corticotropin releasing factor‐neurons of the rat brain

Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine.

Effects of antipsychotic drugs on neurotoxicity, expression of fos-like protein and c- fos mRNA in the retrosplenial cortex after administration of dizocilpine

In this study, we examined the effect of clozapine, olanzapine, risperidone and haloperidol on the neuropathology (i.e. neuronal vacuolization) and the expression of Fos-like protein and c- fos mRNA in the retrosplenial cortex of female Sprague–Dawley rats induced by the NMDA receptor antagonist dizocilpine. Pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, blocked the neuronal vacuolization produced by dizocilpine (0.5 mg/kg, s.c.) in the rat retrosplenial cortex in a dose-dependent manner. Furthermore, pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, significantly attenuated the expression of Fos-like protein in the retrosplenial cortex induced by dizocilpine (0.5 mg/kg, s.c.) in a dose-dependent manner. The marked expression of c- fos mRNA in the rat retrosplenial cortex induced by the administration of dizocilpine (0.5 mg/kg, s.c.) was significantly attenuated by pretreatment (15 min) with clozapine (10 mg/kg) or olanzapine (10 mg/kg), but not risperidone (10 mg/kg) or haloperidol (10 mg/kg). The present results suggest that pharmacologically relevant doses of clozapine or olanzapine, but not risperidone or haloperidol, block the neuropathological changes and the expression of Fos-like protein and c- fos mRNA in the rat retrosplenial cortex elicited by the administration of dizocilpine. It is possible that the blockade of dizocilpine-induced neuropathological changes by clozapine and olanzapine may be related to the unique antipsychotic actions of these drugs in schizophrenic patients, although this remains to be verified.

Light exposure activates retina ganglion cell lysophosphatidic acid acyl transferase and phosphatidic acid phosphatase by a c-fos-dependent mechanism.

We previously reported that the biosynthesis of phospholipids in the avian retina is altered by light stimulation, increasing significantly in ganglion cells in light and in photoreceptor cells in dark. In the present work, we have determined that light significantly increases the incorporation of [3H]glycerol into retina ganglion cell glycerophospholipids in vivo by a Fos-dependent mechanism because an oligonucleotide antisense to c-fos mRNA substantially blocked the light-dark differences. We also studied in vitro the enzyme activities of phosphatidate phosphohydrolase (PAPase), lysophosphatidate acyl transferase (AT II), and phosphatidylserine synthase from retinas of chickens exposed to light or dark. Higher PAPase I and AT II activities were found in incubations of retinal ganglion cells from animals exposed to light; no increase was observed in preparations obtained from light-exposed animals treated with the c-fos antisense oligonucleotide. No light-dark differences were found in phosphatidylserine synthase activity. These findings support the idea that a coordinated photic regulation of PAPase I and AT II is taking place in retina ganglion cells. This constitutes a reasonable mechanism to obtain an overall increased synthesis of glycerophospholipids in stimulated cells that is mediated by the expression of Fos-like proteins.

Fos protein expression induced by intracerebroventricular injection of vasopressin in unconditioned and conditioned mice

Arginine 8–vasopressin (AVP) has been shown to improve memory consolidation in various mnemonic tasks. Our previous studies have pointed out the involvement of the hippocampus in memory consolidation and retrieval processes during discriminative learning by mice. The present study attempts to determine what other brain areas besides the hippocampus might be involved in the enhancing effect of intracerebroventricularly (i.c.v.) injected AVP on memory consolidation in a visual discrimination task using a polyclonal antibody that acts against Fos and Fos-like proteins. For behavioral testing, AVP was i.c.v. injected at the behaviorally active dose of 2 ng after the last learning session and improvement in consolidation processes was assessed in a retention session. Changes in Fos and Fos-like protein expression were determined in non-conditioned and conditioned mice. In non-conditioned mice, AVP i.c.v. injected at a dose of 2 ng evoked a time-dependent increase in Fos and Fos-like protein expression in the dentate gyrus (DG), CA1 and CA3 hippocampal fields, lateral septum (LS), bed nucleus of the stria terminalis, and basolateral and central amygdaloid nuclei, with a peak 120 min after the injection in most of the these brain areas. In contrast, in conditioned mice, an increase in the level of Fos expression, assessed 120 min after the end of learning and the injection of AVP, was detected only in the DG, ventral CA3 hippocampal field, and LS. Thus, the pattern observed after post-training injection of AVP was not the same as that evoked by AVP alone, since among the limbic structures activated following AVP alone, only the DG, the CA3 hippocampal field, and the LS seem to be involved in the enhancing effect of AVP on memory consolidation in discriminative learning.

Effects of Age on Pilocarpine-Induced c- fos Expression in Rat Hippocampus and Cortex

The effect of age on pilocarpine-induced expression of the immediate-early gene c- fos was examined in the hippocampus and cortex of Long-Evans rats. Rats were treated with either pilocarpine (25 mg/kg) or saline, and sacrificed 90 min. following injection. The level of c- fos mRNA and Fos-like protein expression was determined using in situ hybridization histochemistry, and immunocytochemistry, respectively. In saline-treated animals, comparable levels of c- fos mRNA and Fos-like protein were observed in the hippocampus and cortical regions of young (6 month) and aged (24–26 months) rats. The expression of Fos-like protein following pilocarpine treatment was increased, however, in frontal, retrosplenial, and cingulate cortex of aged compared to young rats. In frontal and retrosplenial cortex, the changes in Fos-like protein were accompanied by changes in c- fos mRNA expression. In contrast, no age difference was detected in the hippocampus or parietal cortex of pilocarpine-treated rats. These regionally-specific age differences in response to pilocarpine administration suggest that mechanisms localized to those areas play an important role in determining the response to cholinergic stimulation mediated through post-synaptic muscarinic receptors.

Cortically Driven Immediate-Early Gene Expression Reflects Modular Influence of Sensorimotor Cortex on Identified Striatal Neurons in the Squirrel Monkey

Current understanding of basal ganglia function emphasizes their involvement in the focal, context-dependent release of motor and cognitive circuits in the brainstem and frontal lobes. How such selective action can arise despite the existence of massively convergent inputs from the cerebral cortex is unknown. However, anatomical work has suggested that specificity could be achieved in corticostriatal circuits by modular patterns of convergent and divergent cortical inputs to striatal projection neurons. To test for such modular activation of striatal neurons, we electrically microstimulated physiologically identified sites in the primary somatosensory (SI) and primary motor (MI) cortex of the squirrel monkey. We compared the efferent fiber distributions anterogradely traced from these sites to the distributions of striatal neurons activated by microstimulation to express Fos- and Jun B-like immediate-early gene proteins. We show that the microstimulation of sensorimotor cortex induces Fos and Jun B expression in localized cell clusters in the putamen and that these clusters match the anatomical input fiber clusters (matrisomes). The modular activation of striatal neurons by sensorimotor cortex seems likely. Unexpectedly, >75% of the Fos-positive nuclei in densely labeled cell clusters were in enkephalin-immunoreactive neurons. This expression pattern suggests that the primate sensorimotor cortex exerts a differential influence on the enkephalinergic (indirect pathway) as opposed to the substance P/dynorphin (direct pathway) projection neurons of the putamen. The densely labeled clusters of Fos-labeled enkephalinergic neurons occurred within larger zones containing sparsely distributed Fos-labeled parvalbumin neurons. Moreover, when the cortical stimulation induced expression of Fos-like protein only in sparsely distributed neurons, almost every putamenal neuron expressing Fos was a parvalbumin-containing (GABAergic) interneuron. These patterns suggest a model in which the primate sensorimotor cortex can target parvalbumin-containing inhibitory interneurons, which in turn depress the remaining neuronal activity within and around matrisomes in a feed-forward manner until sufficient coherent cortical input can overcome the inhibition to influence selectively enkephalinergic projection neurons in the activated matrisomes. Tuning of cortical input by striatal interneurons thus may be an important mechanism by which broader anatomical connections are dynamically adjusted to achieve selective flow of information through the basal ganglia.

C-Fos expression as a molecular marker in corticotropin-releasing factor-induced seizures.

Expression of Fos-like protein has been shown to increase after seizures in several types of experimentally induced epilepsies. The intracerebroventricular (icv) injection of murine corticotropin-releasing factor (CRF) in rats (10 micrograms), shows an electroencephalographic (EEG) spiking activity restricted to the amygdaloid-hippocampal area. This EEG seizure pattern represents a unique model of localized epileptic activity induced by a neuropeptide. C-fos expression after icv CRF has been considered a useful tool in mapping areas involved in stress and in seizure activity. Our results show that 1 microgram and 10 micrograms CRF are able to induce c-fos activation in several brain areas. Moreover, the present study not only details c-fos expression increase in brain areas directly involved in spiking activation, such as the amygdaloid-hippocampal region, but also maps the possible contribution of other regions to seizure manifestations.

Neuronal expression of Fos-like protein along the afferent pathway of the milk-ejection reflex in the sheep

This study was designed to reveal the relay stations of the afferent branch of the milk-ejection reflex in the sheep, by examining the effect of nipple stimulation on the expression of Fos protein along the spino-hypothalamic axis. Immunocytochemical detection of Fos protein after manual nipple stimulation in nonlactating ewes revealed intmunolabeled neurons located exclusively ipsilaterally in the 3rd and4th lumbar spinal ganglia, the medial part of laminae I–III of the 3rd and 4th lumbar spinal segments, the lateral cervical nucleus, the dorsal column nuclei, and bilaterally in the hypothalamic paraventricular nucleus. These findings selectively demonstrate for the first time those cell groups mediating the neuroendocrine effects of nipple stimulation.

Involvement of the noradrenergic afferents from the nucleus tractus solitarii to the supraoptic nucleus in oxytocin release after peripheral cholecystokinin octapeptide in the rat.

Activation of abdominal vagal afferents by peripheral injection of cholecystokinin octapeptide induces oxytocin release into the circulation. To test the hypothesis that cholecystokinin increases oxytocin release via activation of noradrenergic afferents from the brainstem, we injected rats with 5-amino-2,4-dihydroxy-alpha-methylphenylethylamine, a selective neurotoxin to noradrenergic fibres, into a lateral cerebral ventricle. The neurotoxin treatment reduced the noradrenaline content in the hypothalamus by 75% and reduced the oxytocin secretion in response to cholecystokinin by over 90%. In separate experiments, the neurotoxin was injected unilaterally in the vicinity of the supraoptic nucleus to test whether direct noradrenergic afferents to the supraoptic nucleus are involved in the response to cholecystokinin. The injection reduced the immunoreactivity for dopamine beta-hydroxylase in the supraoptic nucleus and significantly decreased the number of the supraoptic neurons expressing Fos-like protein after cholecystokinin but not after hypertonic saline. In further experiments, rhodamine-conjugated latex microspheres were injected into the supraoptic nucleus to retrogradely label afferent neurons, and the brains were processed with double-immunohistochemistry for tyrosine hydroxylase and Fos-like protein. In the C2/A2 but not the C1/A1 region of the brainstem, cholecystokinin increased the expression of Fos-like protein in the population of retrogradely-labelled catecholaminergic cells. In the C2/A2 region, the majority of retrogradely labelled cells expressing Fos-like protein after cholecystokinin were catecholaminergic. We conclude that noradrenergic afferents from the A2 but not from the A1 region of the brainstem to the hypothalamus mediate, at least in part, oxytocin release following cholecystokinin.

Brain FOS-like expression in developing and adult honeybees.

This study was undertaken to examine the expression of the protooncogene c-fos in an invertebrate, the honeybee. We investigated first the expression of Fos-like proteins, testing different methodologies (immunohistochemistry, immunocytochemistry, immunoblotting). These studies were carried out at the embryonic, nymphal and adult stages. We found immunoreactive bands at approximately 30 kD and 57 kD. The first ones are revealed at the embryonic, nymphal and adult stages. The approximately 57 kD proteins are present at the adult stage. Beside this qualitative variation, intensive modification occurs with a burst of protein expression a few days after the insect emergence. The results suggest that Fos-like proteins are found in the developing and maturing nervous system. Basal level of expression is found in the olfactory pathway, convincing to explore the protooncogene c-fos expression in the cellular and molecular analyses of olfactory plasticity.

Expression of fos-like protein in brain following sustained hypertension and hypotension in conscious rabbits

The purpose of this study was to examine comprehensively and quantitatively the effects of sustained hypertension and hypotension on neuronal expression of Fos, the protein product of the proto-oncogene c- fos, in the brain of conscious rabbits. Hypertension or hypotension was produced by continuous intravenous infusion of phenylephrine or nitroprusside, at a rate sufficient to increase or decrease, respectively, arterial pressure by 20–30 mmHg, maintained for a period of 60 min. In comparison with a sham control group of rabbits that were infused with the vehicle solution alone, hypertension induced a significant increase in Fos immunoreactivity in the area postrema, the nucleus tractus solitarii, the caudal and intermediate ventrolateral medulla, the lateral parabrachial nucleus and the central nucleus of the amygdala. Double-labelling for tyrosine hydroxylase and Fos immmunoreactivity showed that few (approximately 5%) of the Fos-positive neurons in the caudal and intermediate ventrolateral medulla in this group of animals were also positive for tyrosine hydroxylase. Hypotension also produced a significant increase in Fos immunoreactivity in the above regions, as well as in the rostral ventrolateral medulla, the A5 area, the locus coeruleus and subcoeruleus, the paraventricular nucleus, the supraoptic nucleus, the arcuate nucleus and the medial preoptic area. Approximately 65% of neurons in the rostral, intermediate and caudal ventrolateral medulla that expressed Fos following hypotension were also positive for tyrosine hydroxylase. Similarly, in the pons, approximately 75% of Fos-positive cells in the locus coeruleus, subcoeruleus and A5 area were positive for tyrosine hydroxylase. In the hypothalamus, 92% of Fos-positive neurons in the supraoptic nucleus, and 37% of Fos-positive neurons in the paraventricular nucleus, were immunoreactive for vasopressin. Our results demonstrate that hypertension and hypotension induce reproducible and specific patterns of Fos expression in the brainstem and forebrain. The distribution patterns and chemical characteristics of Fos-positive neurons following sustained hypertension or hypotension are significantly different. In particular, hypotension, but not hypertension, caused Fos expression in many tyrosine hydroxylasepositive cells within all pontomedullary catecholamine cell groups.

Induction of c- fos and CRF mRNA by MK-801 in the parvocellular paraventricular nucleus of the rat hypothalamus

The non-competitive N-methyl- d-aspartate (NMDA) receptor antagonist dizocilpine maleate (MK-801) stimulates the secretion of adrenocorticotropin hormone (ACTH). As corticotropin-releasing factor (CRF) represents the primary modulator of this secretion, we tested the hypothesis that the ability of MK-801 to activate the hypothalamic-pituitary-adrenal (HPA) axis was modulated through actions at the hypothalamic level that modulate the secretion of CRF. Induction of the immediate-early gene c- fos, as well as of CRF mRNA within the paraventricular nucleus (PVN) of the rat hypothalamus, was examined following the intraperitoneally administration of MK-801 (1 mg/kg). MK-801 markedly increased the expression of Fos-like protein in parvocellular nerve cells of the PVN within 60 min of systemic treatment, and double labeling immunocytochemistry indicated that Fos was primarily localized in CRF-containing neurons of the PVN. MK-801 also significantly increased CRF biosynthesis as detected by in situ hybridization, thus suggesting that c- fos could be involved in the regulation of CRF genes. Taken together, these results suggest that MK-801 stimulates the rat HPA axis probably through the neuronal gene expression of PVN CRF. The significance of these data is discussed in terms of hypothalamic NMDA receptor blockade and subsequent transcriptional regulation of CRF by immediate-early genes.

Temporal regulation of light-induced fos and fos-like protein expression in the ventrolateral subdivision of the rat suprachiasmatic nucleus

We measured c- fos messenger RNA levels and Fos protein immunoreactivity in the suprachiasmatic nucleus of rats as a function of light and time of day. Immunohistochemistry demonstrated a daily rhythm of immunoreactive Fos in the ventrolateral subdivision of the suprachiasmatic nucleus of animals entrained to a 12 h/12 h light-dark cycle; expression was low during the dark phase, peaked about 2 h after light onset at dawn, and remained elevated at an intermediate level for the remainder of the light phase. Immunoblots of nuclear extracts showed a 54,000 mol. wt band that increased in density from the dark phase to the early light phase and decreased again during the late light phase. In situ hybridization using a radiolabeled cDNA probe revealed a c- fos messenger RNA signal that was detected as early as 15 min after dawn, prominent at 30 min, and absent by 2 h. The expression of c- fos messenger RNA and Fos immunoreactivity in the suprachiasmatic nucleus depended on the presence of ambient light. In rats entrained to two daily 1-h light pulses corresponding to dawn and dusk (“skeleton” photoperiod) instead of the complete light-dark cycle, immunoreactive Fos was elicited by the dawn pulse alone and was less persistent than during the complete photoperiod. In rats free-running in constant darkness, c- fos messenger RNA and Fos immunoreactivity were stimulated by 2-h light pulses administered only during the subjective night and early subjective day, but not by light pulses during the middle or late subjective day or in the absence of light pulses.

Regional Effects of NMDA Receptor Antagonists on the Induction of Striatal c-fos by Fenfluramine

Induction of the immediate early gene c-fos occurs in striatal nerve cells in response to psychotropic drugs affecting the dopaminergic system. Although this nuclear induction is mediated in part through D 1 receptors, the involvement of N-methyl- d-aspartate (NMDA)-sensitive receptors has been also demonstrated. In the experiments reported here, we examined the effects of the noncompetitive NMDA receptor antagonists ketamine (2 mg/kg; as an anesthetic mixture) and dizocilpine (MK-801; 1 mg/kg), as well as the competitive NMDA receptor antagonist, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 5 mg/kg), on the expression of fos-like protein induced by d l-fenfluramine (20 mg/kg), in the rat caudate putamen. Systemic (IP) administration of the above receptor antagonists 30 min prior to fenfluramine exposure resulted in the blockade of c-fos immunoreactivity. Although the ketamine mixture totally abolished the expression of the immediate early gene, MK-801 and CPP only partially blocked such expression. In addition, pretreatment with the D 1 receptor antagonist SCH 23390 (0.5 mg/kg) also partially suppressed the induction of c-fos by fenfluramine. These findings suggest the participation of NMDA as well as dopamine-sensitive receptors for the induction of striatal c-fos by an indirect serotonergic (5-HT) agonist. The significance of these results is discussed in terms of a possible glutamatergic and dopaminergic mechanism.

Photic induction and circadian expression of Fos-like protein. Immunohistochemical study in the retina and suprachiasmatic nuclei of hamster

Fos-immunohistochemistry was performed in the retina and at four rostro-caudal levels of the suprachiasmatic nuclei (SCN) in hamsters. Animals were sacrificed at four circadian times (CT) relative to activity onset (CT12): CT07, 11, 14, 19 either in permanent darkness (DD) or 1 h after light stimulation. Quantification of immunoreactive nuclei showed (i) endogenous CT related changes exclusively within the rostral SCN with maximum immunoreactivity at CT07, (ii) CT related responses to light in retinal displaced amacrines, ganglion cells and caudal SCN (maximum at CT19), (iii) expression differences in four subsets of SCN cells according to CT. The rostral subset could be implicated in the endogenous clock mechanism since it exhibited a fluctuation of Fos immunoreactivity in DD and expression of Fos protein at CTs 06 and 18 when light provokes transients in the free-running period. In the caudal SCN, a ventro-laterally localized set responded to light at CTs 13 and 18, a dorsal crescent of cells responded only at CT18 and a group located laterally between these two responded at CT18. These cellular subsets may have different functions in the light-entrainment mechanism since light stimuli at CT13 induced phase-delays and, at CT18, phase-advances in the onset of the free-running locomotor activity rhythm.

On the expression of Fos-like protein in the subthalamic nucleus and basal ganglia output systems following kainic acid injections into the rodent striatum

By immunohistochemistry, Fos-like protein induced in response to intrastriatal kainic acid injections was explored in the basal ganglia and the ventrolateral thalamic nucleus of the rat. In the globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata, subthalamic nucleus and ventrolateral thalamic nucleus, Fos was expressed in neuronal cell nuclei showing the maximal number at 4 h and disappeared within 48 h. The substantia nigra pars compacta neurons lacked prominent Fos induction, suggesting that a different mechanism may operate for changes of dopamine systems. Concurrent Fos expression noted in selected regions suggests the link of relay and output stations of the basal ganglia with the ventrolateral thalamus at the early stage of striatal cell degeneration.

Chapter 13 Neurochemically specialized projection neurons of the striatum respond differentially to psychomotor stimulants

The projection neurons of the striatum are uniformly GABAergic, and are of the densely spiny category. Despite their morphological similarities and the commonality of principal neurotransmitter expressed by these neurons, different subtypes of striatal projection neurons have been identified in a wide variety of species through examination of neuropeptide cotransmitters/modulators expressed by these cells: enkephalin-like peptide, neurotensin, and substance P and dynorphin. Not only do different groups of striatal projection neurons express different neuropeptides, they also express, to different degrees, D l -like and D 2 -like dopamine receptor mRNAs. D 1 receptor mRNA expression is prominent in substance P/dynorphin-positive neurons, but D 2 receptor mRNAs are expressed in enkephalinergic projection neurons. In the course of studying the effects of psychomotor stimulants on immediate-early gene expression in the rat striatum, it is noted that even the highest doses of drugs used did not induce Fos-like immunoreactivity in every striatal neuron. This observation leads to the question whether psychostimulants affect only a particular and identifiable subtype of striatal neurons. This chapter tests for such selectivity by analyzing the expression of Fos-like protein in different kinds of striatal interneurons and projection neurons identified with immunostains and histochemical stains.

Expression of Fos-like proteins in gonadotropin-releasing hormone neurons of Syrian hamsters: effects of estrous cycles and metabolic fuels.

In female mammals, reproduction is sensitive to the availability of metabolic fuels, and food deprivation has been shown to suppress pulsatile LH secretion, attenuate the preovulatory LH surge, and prevent ovulation. It has been suggested that food deprivation impairs fertility by reducing the secretion of GnRH by GnRH-producing neurons in the forebrain. A series of experiments tested this hypothesis by examining the effects of estrous cycles and manipulations of metabolic fuel availability on the expression of Fos-like proteins (Fos-IR) in GnRH-immunoreactive (GnRH-IR) neurons in the forebrain of Syrian hamsters. GnRH-IR neurons were detected in several areas, including the diagonal band of Broca (DBB), medial septum (MS), rostral medial preoptic area (mPOA), and caudal POA. In the more rostral regions (DBB and MS/mPOA), GnRH-IR neurons expressed Fos-IR almost exclusively on day 4 of the cycle, just after the preovulatory LH surge. However, in the caudal POA, GnRH-IR neurons expressed Fos-IR across the entire cycle, including days 1-3, when LH secretion is pulsatile. Food deprivation on days 1 and 2 of the cycle, which attenuates the LH surge and blocks ovulation in hamsters, significantly reduced the proportion of GnRH-IR neurons that expressed Fos-IR on days 2 and 4 (caudal POA) or only on day 4 (DBB and MS/mPOA). Suppression of fuel availability with insulin or 2-deoxy-D-glucose on day 1 of the cycle mimicked the effects of food deprivation and reduced the proportion of caudal POA GnRH-IR neurons that expressed Fos-IR. The results of these experiments suggest that in Syrian hamsters, there are separate populations of GnRH-IR neurons associated with pulsatile and surge modes of LH secretion. In addition, the fact that manipulations of metabolic fuel availability cause changes in the expression of Fos-IR in both populations of GnRH-IR neurons provides strong support for the hypothesis that nutritional infertility is due in part to decreased GnRH secretion.