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M Numan

Publications and source records attributed to M Numan.

At least 19 recordsLinked to original sources

Evidence that the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei to inhibit maternal behavior in rats.

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.

Amygdala↗

Using c-Fos immunocytochemistry to identify forebrain regions that may inhibit maternal behavior in rats.

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.

Animals↗

The temporal course of expression of c-Fos and Fos B within the medial preoptic area and other brain regions of postpartum female rats during prolonged mother--young interactions.

Maternal behavior is associated with an increase in the expression of c-Fos and Fos B within neurons of the medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (vBST). Whether this increase wanes as the duration of mother-young interaction increases is unknown. By varying the length of mother-young interactions in postpartum rats, the authors found that within the MPOA/vBST, the levels of both c-Fos and Fos B, once elevated, remained significantly above control levels through 47 hr of pup exposure. The persistence of c-Fos and Fos B within the MPOA/vBST of females that remained with pups was almost unique in that only one other neural area, the anterior magnocellular part of the paraventricular hypothalamic nucleus, showed such a response. Because MPOA/vBST neurons are essential for maternal behavior, the results suggest that c-Fos and Fos B expression within these regions may be necessary to maintain their normal functional activity.

Animals↗

Expression of intracellular progesterone receptors in rat brain during different reproductive states, and involvement in maternal behavior.

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.

Analysis of Variance↗

Expression of c-fos, fos B, and egr-1 in the medial preoptic area and bed nucleus of the stria terminalis during maternal behavior in rats.

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.

Animals↗

Microinjection of the tachykinin neuropeptide K into the ventromedial hypothalamus disrupts the hormonal onset of maternal behavior in female rats.

The medial amygdala exerts an inhibition of maternal behavior in virgin rats, but neither the site to which it projects to exert this effect nor the neurotransmitter used in such a pathway is known. There is also evidence that the ventromedial nucleus of the hypothalamus exerts an inhibition of maternal behavior, and the medial amygdala projects to this nucleus, suggesting that it may receive a projection from the medial amygdala which is inhibitory for maternal behavior. Tachykinin injection into the hypothalamus inhibits reproductive behavior in male rats, and there is a tachykininergic projection from the medial amygdala to the ventromedial hypothalamus. Consequently, the present study was conducted to evaluate the hypothesis that the tachykinin neuropeptide K can inhibit maternal behavior after injection into the ventromedial hypothalamus. Female rats were primed to be maternal by pregnancy termination and estrogen injection. Four doses of the peptide (279 pmol, 186 pmol, 116 pmol, and 66 pmol) were bilaterally injected into the ventromedial hypothalamus, and all were effective in delaying the onset of maternal behavior. Evidence that neuropeptide K disrupts maternal behavior in animals that have already begun to be maternal is also presented. Site specificity of neuropeptide K's effect to within the region of the ventromedial hypothalamus was supported, as injection into the mediodorsal thalamus was without effect. Some possibly relevant neuroendocrine effects are addressed, as well as the possibility that tachykinins may act within the ventromedial hypothalamus to promote virgin female rats' fear of pup odors.

Animals↗

Projection sites of medial preoptic area and ventral bed nucleus of the stria terminalis neurons that express Fos during maternal behavior in female rats.

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.

Animals↗

A lesion and neuroanatomical tract-tracing analysis of the role of the bed nucleus of the stria terminalis in retrieval behavior and other aspects of maternal responsiveness in rats.

The ventral part of the bed nucleus of the stria terminalis forms a junctional region between the medial and lateral preoptic areas. Previous work has shown that the neurons in this region express Fos-like immunoreactivity during maternal behavior, suggesting their involvement in maternal behavior control. Supporting this hypothesis, the first experiment shows that excitotoxic amino acid lesions of the bed nucleus of the stria terminalis disrupt retrieval behavior and other aspects of maternal responsiveness in postpartum rats. The second study traces the efferent projections of the ventral bed nucleus with the anterograde tracer Phaseolis vulgaris leucoagglutinin. The following regions receive strong projections: lateral septum, substantia innominata, paraventricular hypothalamic nucleus, ventral premammillary nucleus, supramammillary nucleus, paraventricular thalamus, ventral tegmental area, periaqueductal gray, retrorubral field, and the region surrounding the locus coeruleus.

Animals↗

Importance of pup-related sensory inputs and maternal performance for the expression of Fos-like immunoreactivity in the preoptic area and ventral bed nucleus of the stria terminalis of postpartum rats.

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.

Animals↗

Expression of Fos-like immunoreactivity in the preoptic area of maternally behaving virgin and postpartum rats.

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.

Amygdala↗

A neural circuitry analysis of maternal behavior in the rat.

This article reviews work that shows that the medial preoptic area of the hypothalamus plays a crucial role in controlling the occurrence of maternal behavior in rats. A primary goal of this report is to fit the medial preoptic area into a larger neural circuitry, examining its critical inputs and outputs. Lesions of the medial preoptic area disrupt maternal behavior and estradiol and prolactin injections into this region activate maternal behavior. The medial amygdala, which is located in the limbic telencephalon, sends a neural projection to the preoptic region. Research indicates that this projection influences maternal behavior by relaying olfactory input to the medial preoptic area. The output of the preoptic area influences maternal behavior through descending projections to the brain stem. One of the influences of such projections might be to regulate neural circuits involved in controlling specific maternal responses, such as retrieval (carrying of pups) behavior.

Algorithms↗

Excitotoxic amino acid injections into the medial amygdala facilitate maternal behavior in virgin female rats.

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.

Amygdala↗

Preoptic-brainstem connections and maternal behavior in rats.

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.

Animals↗

Long-term effects of preoptic area knife cuts on the maternal behavior of postpartum rats.

Knife cuts severing the lateral connections of the medial preoptic area disrupt maternal behavior in postpartum rats. In these studies the knife cuts were produced 1-2 days prior to behavioral testing. The present study examined whether preoptic area knife cuts produce long-term deficits in maternal behavior. Nulliparous Charles River CD rats received knife cuts severing the lateral connections of the medial preoptic area or sham cuts. Approximately 2 weeks later they were mated. All females delivered young 22-23 days after mating, and litter size did not differ between the groups. Females with preoptic knife cuts cleaned their young, built nests (albeit of inferior quality), crouched over their young in a nursing posture, and lactated. The major deficit shown was the near total elimination of retrieval behavior. Females with preoptic knife cuts, however, were capable of performing the oral-motor responses associated with hoarding behavior. These results show that severing the lateral connections of the medial preoptic area does produce long-term deficits in maternal behavior, particularly with respect to maternal retrieving.

Animals↗

Dorsolateral connections of the medial preoptic area and maternal behavior in rats.

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.

Animals↗

Central prolactin infusions stimulate maternal behavior in steroid-treated, nulliparous female rats.

A series of experiments were conducted to determine whether and under what conditions central prolactin (PRL) administration would stimulate the onset of maternal behavior in female rats and to identify possible neural sites of PRL action. In each experiment ovariectomized, nulliparous rats whose endogenous PRL levels were suppressed with bromocriptine were tested for maternal behavior toward foster young. In experiments 1, 2, and 4, females were also exposed to pregnancy-like levels of progesterone (days 1-11) followed by estradiol (days 11-17). In experiment 1 infusions (days 11-13) of four doses of ovine PRL (400 ng, 2 micrograms, 10 micrograms, or 50 micrograms, but not 80 ng) into the lateral ventricle resulted in a rapid onset of maternal behavior (behavioral testing, days 12-17). The stimulatory action of these doses of PRL appears to be central, since subcutaneous injections of 50 micrograms of ovine PRL failed to affect maternal responsiveness (experiment 2). Experiment 3 indicated that the stimulatory effect of intracerebroventricularly administered PRL is steroid dependent. Infusions of either 10 micrograms of ovine PRL or 10 micrograms of rat PRL failed to induce maternal behavior in nonsteroid-treated animals. In the final experiment (no. 4) bilateral infusions of 40 ng of ovine PRL into the medial preoptic area of steroid-treated rats resulted in a pronounced stimulation of maternal behavior. These findings demonstrate a central site of PRL action in the stimulation of maternal responsiveness and point to the medial preoptic area as a key neural site for PRL regulation of maternal behavior.

Animals↗