RESUMEN
The maternal behaviors shown by a rat that has given birth are not shown by a virgin female rat when she is first presented with young. This absence of maternal behavior in virgins has been attributed to the activity of a neural circuit that inhibits maternal behavior in nulliparae. The medial amygdala and regions of the medial hypothalamus such as the anterior and ventromedial hypothalamic nuclei have previously been shown to inhibit maternal behavior, in that lesions to these regions promote maternal responding. Furthermore, we have recently shown that these and other regions, such as the principal bed nucleus of the stria terminalis, the ventral lateral septum, and the dorsal premammillary nucleus, show higher pup-induced Fos-immunoreactivity in non-maternal rats exposed to pups than during the performance of maternal behavior, indicating that they too could be involved in preventing maternal responsiveness. The current study tested whether the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei in a neural circuit that inhibits maternal behavior, as well as to see what other brain regions could participate in this circuit. Bilateral excitotoxic lesions of the medial amygdala, or of the anterior/ventromedial hypothalamic nuclei, promoted maternal behavior. Unilateral medial amygdala lesions caused a reduction of pup-induced Fos-immunoreactivity in the anterior/ventromedial hypothalamic nuclei in non-maternal rats ipsilateral to the lesion, as well as in the principal bed nucleus of the stria terminalis, ventral lateral septum, and dorsal premammillary nucleus. Finally, unilateral medial amygdala lesions paired with contralateral anterior/ventromedial hypothalamic nuclei lesions promoted maternal behavior, although ipsilateral lesion placements were also effective.Together, these results indicate that the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei in a neural circuit that inhibits maternal behavior, and that the principal bed nucleus of the stria terminalis, ventral lateral septum, and dorsal premammillary nucleus could also be involved in this circuit.
Asunto(s)
Amígdala del Cerebelo/citología , Núcleo Hipotalámico Anterior/citología , Conducta Materna/fisiología , Inhibición Neural/fisiología , Vías Nerviosas/citología , Ratas Sprague-Dawley/metabolismo , Núcleo Hipotalámico Ventromedial/citología , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Animales , Animales Recién Nacidos/fisiología , Núcleo Hipotalámico Anterior/efectos de los fármacos , Núcleo Hipotalámico Anterior/metabolismo , Recuento de Células , Desnervación , Femenino , Lateralidad Funcional/efectos de los fármacos , Lateralidad Funcional/fisiología , Inmunohistoquímica , Conducta Materna/efectos de los fármacos , Inhibición Neural/efectos de los fármacos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/metabolismo , Neurotoxinas/farmacología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Sprague-Dawley/anatomía & histología , Núcleo Hipotalámico Ventromedial/efectos de los fármacos , Núcleo Hipotalámico Ventromedial/metabolismoRESUMEN
Evidence indicates there is a neural system that inhibits maternal behavior in virgin rats. It has been suggested that pregnancy hormones promote the onset of maternal behavior by reducing the behavioral influence of this system. The authors used c-Fos immunocytochemistry to identify brain regions more activated by pup exposure in nonmaternal rats than in maternal rats. Previous experiments indicated that some of these regions, such as the posterodorsal medial amygdala and several medial hypothalamic sites, inhibit maternal behavior. For others, such as the ventral lateral septum, dorsal premammillary nucleus, and principal bed nucleus of the stria terminalis, this is the first indication that they could also inhibit maternal responding. These regions have previously been implicated in promoting defensive behaviors, consistent with the finding that nonmaternal rats actively avoid pups. These findings suggest the existence of a neural circuit through which pup exposure could promote defensive responses in virgin rats, and how pregnancy hormones could reduce such activity to stimulate maternal behavior.
Asunto(s)
Conducta Materna/fisiología , Inhibición Neural/fisiología , Prosencéfalo/fisiología , Proteínas Proto-Oncogénicas c-fos/análisis , Animales , Mapeo Encefálico , Femenino , Técnicas para Inmunoenzimas , Red Nerviosa/fisiología , Embarazo , Prosencéfalo/anatomía & histología , Ratas , Ratas Sprague-DawleyRESUMEN
Progesterone is one of a complex of hormones which influences the occurrence of maternal behavior in rats. The present study provides information on progesterone's mechanism and possible neural site(s) of action with respect to maternal responsiveness. Progesterone can exert cellular effects by acting on membrane receptors or by acting on intracellular receptors. In the first experiment we show that RU 486 can antagonize progesterone's inhibitory effect on maternal behavior. Since RU 486 acts as an antagonist to progesterone's action at its intracellular receptor, these results support the involvement of that receptor in maternal behavior control. The second experiment employs immunocytochemical techniques to detect the number of cells in various forebrain regions which contain intracellular progesterone receptors during different reproductive states. The number of cells which contained progesterone receptors was higher toward the end of pregnancy (progesterone is presumably exerting its effects on maternal behavior at this time) when compared to either early pregnancy or lactation in the following forebrain regions: anteroventral periventricular nucleus of the preoptic area; medial preoptic area; ventral part of the bed nucleus of stria terminalis; ventrolateral division of the ventromedial nucleus; arcuate nucleus; anterior paraventricular nucleus of the hypothalamus; and medial amygdala. The possible involvement of these regions as a site or sites where progesterone might exert its effects on maternal behavior is discussed.
Asunto(s)
Química Encefálica/fisiología , Conducta Materna , Receptores de Progesterona/análisis , Reproducción/fisiología , Análisis de Varianza , Animales , Femenino , Antagonistas de Hormonas/farmacología , Inmunohistoquímica , Mifepristona/farmacología , Embarazo , Ratas , Receptores de Progesterona/antagonistas & inhibidoresRESUMEN
The spatial and temporal pattern of expression of the protein products of immediate early genes (IEGs) c-fos, fos B, and egr-1 were mapped in medial preoptic area (MPOA) and ventral bed nucleus of stria terminalis (VBST) during maternal behavior in rats. Immunocytochemical analysis indicated significant increases in the number of cells expressing c-Fos after 2 h of pup exposure, while Fos B levels showed a delayed response, reaching maximal levels after 6 h.
Asunto(s)
Proteínas de Unión al ADN/biosíntesis , Proteínas Inmediatas-Precoces , Conducta Materna/fisiología , Área Preóptica/metabolismo , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Factores de Transcripción/biosíntesis , Animales , Conducta Animal/fisiología , Proteínas de Unión al ADN/análisis , Proteína 1 de la Respuesta de Crecimiento Precoz , Femenino , Genes Inmediatos-Precoces/fisiología , Área Preóptica/química , Proteínas Proto-Oncogénicas c-fos/análisis , Ratas , Ratas Endogámicas , Factores de Transcripción/análisis , Dedos de Zinc/fisiologíaRESUMEN
Medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (VBST) neurons are involved in maternal behavior, but the neural sites to which the maternally relevant neurons project have not been determined. Since MPOA and VBST neurons express Fos during maternal behavior, we used a double-labeling immunocytochemical procedure to detect both Fos and a retrograde tracer, wheat germ agglutinin (WGA), in order to determine where these Fos neurons project. On Day 4 postpartum, fully maternal females were separated from their litters. On Day 5, WGA was iontophoretically injected into one of the following regions known to receive MPOA and/or VBST input: Lateral septum, medial hypothalamus at the level of the ventromedial nucleus, lateral habenula, ventral tegmental area, retrorubral field, or periaqueductal gray. On Day 7, females received a 2-h test with either pups or candy, after which they were perfused and their brains were processed for the detection of Fos and WGA. As expected, females tested with pups had more Fos-containing neurons in the MPOA and VBST than did females tested with candy. After WGA injections into several brain sites, the number of double-labeled cells observed in the MPOA and VBST was greater for the maternal females when compared to the non-maternal females. Therefore, these results pinpointed neural circuits that were activated during maternal behavior. For the maternal females, Fos-containing neurons in the MPOA projected most strongly to the medial hypothalamus at the level of the ventromedial nucleus and to the lateral septum, while Fos-containing neurons in the VBST projected most strongly to the retrorubral field, ventral tegmental area, and medial hypothalamus. Although relatively few MPOA and VBST neurons which expressed Fos during maternal behavior projected to the periaqueductal gray, these Fos-expressing neurons made up a relatively large proportion of the MPOA and VBST projection to the periaqueductal gray. This study suggests that MPOA and VBST efferents project to a variety of regions to promote full maternal responsiveness.
Asunto(s)
Hipotálamo/fisiología , Conducta Materna/fisiología , Proteínas del Tejido Nervioso/biosíntesis , Neuronas/fisiología , Área Preóptica/fisiología , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Animales , Femenino , Hipotálamo/citología , Inmunohistoquímica , Vías Nerviosas/fisiología , Ratas , Aglutininas del Germen de TrigoRESUMEN
This study used Fos immunocytochemistry to locate neurons within the medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (VBNST) that are tightly associated with the performance of maternal behavior in postpartum rats. In the first experiment, a high degree of Fos activation was observed in these regions if females were allowed to interact fully with pups, but not if they could receive only olfactory, visual, and auditory inputs from pups. The second experiment found that olfactory bulbectomy combined with thelectomy did not eliminate Fos expression in the MPOA and VBNST of females displaying maternal behavior. These Fos-expressing neurons may represent efferent neurons essential for the performance of maternal behavior.
Asunto(s)
Tronco Encefálico/fisiología , Conducta Materna/fisiología , Área Preóptica/anatomía & histología , Proteínas Proto-Oncogénicas c-fos/genética , Sensación/fisiología , Área Tegmental Ventral/fisiología , Animales , Mapeo Encefálico , Vías Eferentes/fisiología , Femenino , Expresión Génica , Técnicas para Inmunoenzimas , Masculino , Bulbo Olfatorio/anatomía & histología , Embarazo , Ratas , Privación Sensorial/fisiología , Olfato/fisiologíaRESUMEN
This study uses Fos immunocytochemistry to show that the medial preoptic area and ventral bed nucleus of the stria terminalis are activated in maternally behaving female rats. In Experiment 1, virgin female rats that showed maternal behavior toward pups had more cells in these regions that expressed Fos-like immunoreactivity than did virgin females that were not maternally responsive. In Experiment 2, postpartum rats that were exposed to pups and showed maternal behavior had more Fos-labeled cells in these regions than did postpartum rats exposed to candy. Evidence also indicated that functional modifications in the medial amygdala were related to the changes in Fos expression observed in the preoptic area and ventral bed nucleus of the stria terminalis.
Asunto(s)
Conducta Materna , Preñez/fisiología , Área Preóptica/fisiología , Proteínas Proto-Oncogénicas c-fos/genética , Amígdala del Cerebelo/fisiología , Animales , Mapeo Encefálico , Femenino , Regulación de la Expresión Génica/fisiología , Técnicas para Inmunoenzimas , Neuronas/fisiología , Embarazo , Ratas , Medio SocialRESUMEN
The inhibitory role of the medial amygdala (MA) in maternal behavior control was explored. Injections of N-methyl-D,L-aspartic acid (NMA), an excitotoxic amino acid, into the MA resulted in a dramatic facilitation of maternal behavior in virgin female rats when pups were presented to them 12 days following the injections. This effect was specific to MA in that NMA injections into the basolateral amygdala were ineffective. The facilitatory effect of NMA injections into MA was found to be hormone dependent in that ovariectomies abolished the effect. Subsequent experiments provided evidence that NMA injections into MA induced a pseudopregnant state lasting about 13 days, and that maternal behavior was greatly facilitated only when pups were presented to such females coincident with pseudopregnancy termination. When pups were presented 24 days following injections of NMA into MA, rather than 12 days, only a modest facilitation of maternal behavior was observed. It was concluded that NMA injections into MA influence maternal behavior in two ways: By inducing an hormonal state stimulatory for maternal behavior and by removing neural inhibition over maternal behavior.
Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Conducta Materna , N-Metilaspartato/farmacología , Inhibición Neural/efectos de los fármacos , Amígdala del Cerebelo/fisiología , Animales , Mapeo Encefálico , Bromocriptina/farmacología , Estro/efectos de los fármacos , Estro/fisiología , Femenino , N-Metilaspartato/fisiología , Inhibición Neural/fisiología , Seudoembarazo/fisiopatología , Ratas , Maduración Sexual/efectos de los fármacos , Maduración Sexual/fisiología , Medio SocialRESUMEN
This study presents evidence supporting the view that preoptic area (POA) projections through the ventral tegmental area (VTA) to lower brainstem regions are important for maternal behavior in postpartum rats. Experiment 1 demonstrated that bilateral coronal knife cuts posterior to the VTA disrupted maternal behavior, and Experiment 2 demonstrated a similar disruption when a unilateral knife cut that severed the lateral connections of the medial POA was paired with a contralateral knife cut posterior to the VTA. In a final anatomical experiment using horseradish peroxidase histochemistry, it was shown that knife cuts posterior to the VTA do sever POA efferents. However, such cuts severed other ascending and descending pathways as well, and these may also be involved in maternal behavior control.
Asunto(s)
Tronco Encefálico/fisiología , Conducta Materna , Área Preóptica/fisiología , Transmisión Sináptica/fisiología , Animales , Mapeo Encefálico , Vías Eferentes/fisiología , Femenino , Lactancia/fisiología , Fibras Nerviosas/fisiología , Comportamiento de Nidificación/fisiología , Neuronas/fisiología , Ratas , Tegmento Mesencefálico/fisiologíaRESUMEN
The lateral connections of the medial preoptic area (MPOA) are essential for maternal behavior in rats. The purpose of this study was to more exactly specify the nature of this pathway. Experiment 1 found that knife cuts that severed the dorsolateral connections of the MPOA were as effective as complete cuts in disrupting maternal behavior, whereas knife cuts that severed the ventrolateral MPOA connections were ineffective. These results suggest that MPOA efferents and afferents critical for maternal behavior leave or enter the MPOA dorsolaterally. Experiment 2 located possible sources of critical afferent input. Lactating rats received MPOA lateral cuts with a horseradish peroxidase (HRP)-coated wire knife. Full lateral cuts and dorsolateral cuts disrupted maternal behavior and labeled more cells with HRP in the nucleus of the solitary tract and the locus coeruleus than did ventrolateral cuts, which did not disrupt maternal behavior.
Asunto(s)
Área Hipotalámica Lateral/fisiología , Conducta Materna , Área Preóptica/fisiología , Animales , Mapeo Encefálico , Femenino , Lactancia/fisiología , Comportamiento de Nidificación/fisiología , Vías Nerviosas/fisiología , Neuronas/fisiología , Embarazo , RatasRESUMEN
In this study we investigated the effects of axon-sparing lesions of the preoptic region on the maternal behavior of postpartum rats. The lesions were produced with the excitotoxic amino acid N-methyl-D,L-aspartic acid (NMA). The first experiment determined that bilateral injections of NMA into the medial preoptic area (MPOA) of fully maternal lactating rats disrupted maternal behavior. In a second experiment, bilateral injections of NMA into the lateral preoptic area and adjoining substantia innominata (LP/SI region) also disrupted maternal behavior. A third experiment, employing horseradish peroxidase histochemistry, provided anatomical evidence that NMA destroys neuronal cell bodies while sparing fibers of passage. These findings were discussed with respect to the view that an MPOA-to-LP/SI-to-ventral tegmental area circuit underlies maternal behavior in the rat.