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Contains fulltext : 133842.pdf (Publisher’s version ) (Closed access) The sequential organization of sexual behavior of the female rat is described, eventually leading to the lordotic posture, shown during mating. A complex set of signals: olfactory, cutaneous sensory as well as genitosensory, is guiding the female to this specific posture, eventually. Genitosensory signals converge in the lumbosacral levels of the spinal cord, from where they are dispersed to a series of supraspinal brain areas, in the brainstem, thalamus, hypothalamus and limbic system. The similarity with the neural activation patterns observed in the male rat is remarkable. In a number of brain areas, however: the midbrain periaqueductal gray, the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) and the medial preoptic-lateral septum regions, specific male-female differences have been observed. Especially the VMHvl is an intriguing area, as it has been shown that the same neurons may be involved in 'opposite behavior' like aggression and the induction of lordosis. The motor mechanisms controlling the lordosis posture in the rat as well as in some other mammals are discussed, as well as some aspects of the reward mechanisms contributing to female sex. We conclude that we have collected a great amount of neurophysiological knowledge over the last 20 years, but that the unresolved questions are still numerous. In this field, there is still much to explore. 01 juni 2014

The neural projection of the lateral septum (LS) to the rostral mesencephalic central gray (MCG) is sexually dimorphic and plays an important role in inhibiting female reproductive behavior. In this experiment, development of the LS-MCG connection from birth to 15 days after birth was examined in female rats by a tract-tracing method with DiI. On the birth day (D1 rat), and 5, 10 or 15 days after birth (D5, D10 or D15 rat, respectively) or 8 weeks after birth (adult), the brain was fixed by perfusion of a mixture of 4% PFA and 0.1% glutaraldehyde. DiI was pasted on the coronally cut-surface of the LS and the sample was incubated in PFA at 40 degrees C for up to 4 months. After incubation, 200-microm frozen parasagittal sections were prepared and observed by fluorescence microscopy. As a result, numerous DiI labeled fibers were found in the preoptic area, the anterior and posterior hypothalamus, and the MCG in adult rats. In D1 rats, several labeled axons extended caudal to the anterior hypothalamic area. In D5 rats, a few labeled fibers reached the MCG. Some labeled fibers were observed in the rostral MCG of D10 rats. In D15 rats, a considerable number of labeled fibers were seen to reach the rostral MCG and relative density of the fibers was comparable to that of adult. These results suggest that the neural pathway from the LS to the rostral MCG develops acutely during the period from 5-10 days up to more than 15 days after birth.

During the 25 years since a motivational systems model was proposed to explain the brain mechanisms of aggressive behavior (D.B. Adams. Brain mechanisms for offense, defense, and submission. Behav. Brain. Sci. 2, (1979a) 200-241) considerable research has been carried out. Updating the model in the light of this research requires several changes. A previous distinction between submission and defense systems is abandoned and, instead, it is proposed that two distinct subsets of the defense motivational mechanism may be recognized, one for anti-predator defense and the other for consociate defense. Similarly, the offense motivational mechanism is now considered to have at least two subsets, one mediating territorial and the other competitive fighting. Data continue to indicate that the defense motivational mechanism is located in the midbrain central gray and adjoining tissue. Also data tend to support the hypothesis that the offense motivational mechanism is located in the hypothalamus at the level of the anterior hypothalamus. Consideration is also given to a motivational system for patrol/marking which is related to aggressive behavior. Research is reviewed that bears on the neural structure of motivating and releasing/directing stimuli and motor patterning mechanisms of offense, defense and patrol/marking, as well as the location of learning and hormonal effects, and attention is given to how the model can be tested.

Sex difference in the number of neurons projecting axons from the lateral septum (LS) to the midbrain central gray (MCG) that are concerned with the lordosis-inhibiting system was investigated by injection of Fluoro-Gold (FG), a retrograde tracer, into the rostral MCG on the right side in male and female rats. Immunohistochemistry for ER- and - was also performed with or without combination with FG immunostaining. All animals were gonadectomized. Lordosis was observed after treatment with E2 in some animals. In the results, lordosis was rare in males, compared with females. FG-immunoreactive (ir) cells were concentrated in the intermediate LS on the right side, and its number in the females was significantly higher than that in the males. There was no sex difference in the distribution and number of ER-ir and ER-ir cells in the LS. Furthermore, the number of ERs-ir cells was not influenced by E2 in either males or females. Double FG-ER-ir cells were less than 20% of total FG-ir cells in the LS in both males and females. These data suggest that the LSMCG connection is sexually dimorphic but that there is no sex difference in the expression of ERs in the LS. (Endocrinology 143: 285–294, 2002)

Reproductive behavior in most mammalian species consists of a highly stereotyped pattern of movements, is elicited by specific sensory stimuli and is sex steroid dependent. The present paper describes a concept of the pathways in the midbrain, brainstem and spinal cord which control the receptive posture of the female cat. The midbrain periaqueductal gray (PAG), which is an important structure in the Emotional Motor System (EMS), receives direct input from a distinct group of neurons in the dorsal horn of the lumbosacral cord. This cell group overlaps with the location of pelvic and to lesser extent, pudendal nerve primary efferents, which convey information from the pelvic viscera and sex organs to the central nervous system. The FAG, in turn, controls various motor components of female receptive behavior using different pathways. For example, immobility, which is one of the characteristics of receptive behavior, might be mediated by a diffuse pathway from the FAG, via the ventral part of the medial medullary tegmentum, to all parts of the spinal ventral hem. More specific components, such as hindlimb treading, lateral deviation of the tail and elevation of the lower back, are thought to be controlled by a circumscribed projection from the FAG to the nucleus retroambiguus (NRA). The NRA is a group of interneurons at the transition between brainstem and spinal cord and projects directly to distinct lumbosacral motoneuronal cell groups, which innervate muscles that are likely to be involved in the female receptive posture. Estrogen induces axonal sprouting of the NRA-lumbosacral pathway in adult female cats, which explains why female cats only display receptive behavior when estrogen levels are high. (C) 1998 Elsevier Science B.V. All rights reserved.

Reproductive behavior in most mammalian species consists of a highly stereotyped pattern of movements, is elicited by specific sensory stimuli and is sex steroid dependent. The present paper describes a concept of the pathways in the midbrain, brainstem and spinal cord which control the receptive posture of the female cat. The midbrain periaqueductal gray (PAG), which is an important structure in the Emotional Motor System (EMS), receives direct input from a distinct group of neurons in the dorsal horn of the lumbosacral cord. This cell group overlaps with the location of pelvic and to lesser extent, pudendal nerve primary efferents, which convey information from the pelvic viscera and sex organs to the central nervous system. The FAG, in turn, controls various motor components of female receptive behavior using different pathways. For example, immobility, which is one of the characteristics of receptive behavior, might be mediated by a diffuse pathway from the FAG, via the ventral part of the medial medullary tegmentum, to all parts of the spinal ventral hem. More specific components, such as hindlimb treading, lateral deviation of the tail and elevation of the lower back, are thought to be controlled by a circumscribed projection from the FAG to the nucleus retroambiguus (NRA). The NRA is a group of interneurons at the transition between brainstem and spinal cord and projects directly to distinct lumbosacral motoneuronal cell groups, which innervate muscles that are likely to be involved in the female receptive posture. Estrogen induces axonal sprouting of the NRA-lumbosacral pathway in adult female cats, which explains why female cats only display receptive behavior when estrogen levels are high. (C) 1998 Elsevier Science B.V. All rights reserved.

In 1995, we discovered a new pathway in the cat, which originates from the nucleus retroambiguus (NRA) and terminates in a distinct set of lumbosacral hindlimb, axial, and pelvic floor motoneuronal cell groups [VanderHorst VG.JM, Holstege G (1995) Caudal medullary pathways to lumbosacral motoneuronal cell groups in the cat: evidence for direct projections possibly representing the final common pathway for lordosis. J Comp Neurol 359:457-475]. The NRA is a compact group of interneurons located laterally in the caudal medulla oblongata. Its projection to lumbosacral moloneurons is thought to represent the final common pathway for male mounting and for female receptive or lordosis behavior. However, females only display lordosis behavior when they are in estrus, which suggests that the NRA-lumbosacral pathway is only active during estrus. This raised the question of whether estrogen affects this pathway. The effect of estrogen on the NRA-lumbosacral projection was studied light microscopically, using wheat-germ agglutinin horseradish peroxidase (WGA-HRP) as a tracer. The rubrospinal pathway served as control. The density of labeled NRA fibers in their target hindlimb motoneuronal cell groups appeared abundant in estrous and very weak in nonestrous cats. Such differences were not found in the rubrospinal pathway. For electron microscopical study, the NRA projection to the semimembranosus motoneuronal cell group was selected. In this cell group, an almost ninefold increase of labeled profiles was found in estrous versus nonestrous cats. Moreover, the semimembranous motoneuronal cell group contained labeled growth cones in estrous, but not in nonestrous, cats. The present study is the first to show that estrogen induces axonal outgrowth of a precisely identified pathway in the adult mammalian central nervous system. The possible mechanisms underlying this outgrowth are discussed.

The effects of stimulating the midbrain central gray matter (CGM) on motoneuronal response in trigeminal nerves were investigated in anesthetized cat. It was found that stimulating the CGM did not induce postsynaptic response in these motoneurones. Conditioning stimulation of the CGM brought about suppression of motoneuronal postsynaptic response to stimulation of tooth pulp and high threshold infraorbital nerve afferents without affecting motoneuronal antidromic response and jaw-opening reflex as induced by stimulating the caudal nucleus of the spinal trigeminal tract. It was thus concluded that stimulating the CGM exerts no direct effect on motoneurons but does have an influence on postsynaptic response — a result of modulation of the afferent spike flow at interneuronal level.

Locomotor stepping in the Nembutal-anesthetized rat was elicited by electrical stimulation of either of two sites in the right or left posterolateral hypothalamus. Essential midbrain loci were identified by reversibly blocking the elicited locomotion through local injections of the anesthetic procaine (15%, 0.5 μl). Two types of critical midbrain sites were found. At ipsilateral block sites (n = 21), procaine blocked only that locomotion elicited by ipsilateral stimulation. These sites could be along the course of a direct descending ipsilateral pathway although a possible bidirectional pathway is not to be excluded. At bilateral block sites (n = 21), procaine blocked locomotion elicited by both ipsilateral and contralateral stimulation. These sites could be involved in functions prerequisite for the initiation of locomotion or in the generation of the stepping pattern. Procaine injections in 35 sites had no effect on locomotion. Ipsilateral and bilateral block sites were intermixed and generally located in regions ventral to the midbrain central gray: chiefly the anterior ventromedial midbrain, the pontis oralis nucleus and the pedunculopon-tine nucleus. Negative sites were located in both the dorsal and ventral midbrain. Ipsilateral block sites were relatively prevalent in the anterior midbrain, indicating that the locomotor initiation signals are lateralized at this level. Bilateral block sites were more prevalent in the posterior levels, suggesting that the initiation signals are proximal to, or interact with, circuits that have a bilateral influence on locomotion.

In 1995, we discovered a new pathway in the cat, which originates from the nucleus retroambiguus (NRA) and terminates in a distinct set of lumbosacral hindlimb, axial, and pelvic floor motoneuronal cell groups [VanderHorst VGJM, Holstege G (1995) Caudal medullary pathways to lumbosacral motoneuronal cell groups in the cat: evidence for direct projections possibly representing the final common pathway for lordosis. J Comp Neurol 359:457-475]. The NRA is a compact group of interneurons located laterally in the caudal medulla oblongata. Its projection to lumbosacral motoneurons is thought to represent the final common pathway for male mounting and for female receptive or lordosis behavior. However, females only display lordosis behavior. However, females only display lordosis behavior when they are in estrus, which suggests that the NRA-lumbosacral pathway is only active during estrus. This raised the question of whether estrogen affects this pathway. The effect of estrogen on the NRA-lumbosacral projection was studied light microscopically, using wheat-germ agglutinin horseradish peroxidase (WGA-HRP) as a tracer. The rubrospinal pathway served as control. The density of labeled NRA fibers in their target hindlimb motoneuronal cell groups appeared abundant in estrous and very weak in nonestrous cats. Such differences were not found in the rubrospinal pathway. For electron microscopical study, the NRA projection to the semi-membranosus motoneuronal cell group was selected. In this cell group, an almost ninefold increase of labeled profiles was found in estrous versus nonestrous cats. Moreover, the semimembranous motoneuronal cell group contained labeled growth cones in estrous, but not in nonestrous, cats. The present study is the first to show that estrogen induces axonal outgrowth of a precisely identified pathway in the adult mammalian central nervous system. The possible mechanisms underlying this outgrowth are discussed.

This study has sought to identify hypothalamic pathways mediating flight behavior in the cat. Flight behavior, characterized by an initial pupillary dilatation and followed by vigorous attempts to leap out of the observation chamber, was elicited primarily by electrical stimulation of the medial preoptic region and dorsomedial hypothalamus, and to a lesser extent from the perifornical region. A [14C]-2-deoxyglucose analysis was utilized to examine brain regions functionally activated by stimulation of hypothalamic sites which elicited flight behavior. In a second series of experiments, [3H]leucine injected into regions surrounding electrode tips from which flight had previously been elicited, permitted identification of pathways arising from such functionally characterized sites. We describe for the first time pathways arising from the hypothalamus which mediate flight behavior. In spite of individual variation in placement of electrodes eliciting flight, a consistent pattern of labeling was observed following injection of either [14C]-2-deoxyglucose systemically or [3H]amino acids into the hypothalamus. The primary rostal target structures receiving inputs from flight electrode sites included the nuclei of the diagonal band, bed nucleus of the stria terminalis, medial amygdaloid nucleus, lateral septal nucleus, and anterior medial preoptico-hypothalamus. Caudal to the level of stimulation, the principal target nuclei involved the centrum medianum-parafascicular complex and the midbrain central gray substance. Possible roles of these nuclear regions in organization and regulation of flight behavior is discussed.

Small lesions in the most posterior portion of the globus pallidus and adjacent internal capsule virtually eliminated fear or defensive reactions in wild Norway rats. Flight to an approaching experimenter, startle reactions to dorsal and vibrissae contacts, defensive attack to a conspecific and reactions to handling by human experimenters were grossly reduced following surgery and for a period of 30 days thereafter. After tail shock, however, some defensive behaviors reappeared. This pattern of behavior changes suggests a striking similarity between effects of the present small lesions and the “amygdala-lesion syndrome” of reduced defensiveness to nonpainful stimuli. It is also similar but not identical to the reduced defensiveness which follows damage to the midbrain central gray, with the difference between the two lesions suggesting that more complex fear-eliciting stimuli are processed at the higher site.

The peroxidase-antiperoxidase immunocytochemical method was used to determine quantitatively the effects of gonadal steroids on the immunoreactive luteinizing hormone-releasing hormone (LHRH) content

Recent studies involving visual and nonvisual discrimination habits suggest that the components of the rodent’s general (nonspecific) learning system (a group of brain structures essential for normal acquisition of a wide range of laboratory tasks) include the regions of the globus pallidus, lateral thalamus, substantia nigra, midbrain central gray, median raphe, and pontine reticular formation. To determine whether these regions play a role in more complex kinds of learning, young rats previously subjected to selective lesions to these brain sites received five trials on each of three “climbing” detour problems. Performance on Trial 1 (a measure of response flexibility) as well as performance on Trials 2–5 (a measure of detour habit formation) of each problem was significantly impaired in those groups with damage to the globus pallidus, substantia nigra, median raphe, or pontine reticular formation. On the other hand, those groups with damage to the lateral thalamus or midbrain central gray failed to display consistent deficits in detour problem-solving behavior. This pattern of results suggests that the latter two structures can no longer be grouped with the globus pallidus, substantia nigra, median raphe, and pontine reticular formation as components of the rodent’s general learning system.

It has been assumed that the components of the rodent’s “general learning system” (a group of brain structures essential for normal acquisition of a wide range of laboratory tasks) can roughly be identified by determining which lesion placements within the rat brain will lead to defective acquisition of a spatial discrimination habit and its reversal as well as a brightness discrimination habit and its reversal. The results of this experiment suggest that the regions of the posterolateral hypothalamus and mesencephalic central gray, but not the regions of the nucleus accumbens, septofornix, medial supraoptic area, or ventromedial hypothalamus, qualify as components of the general learning system.

Rats chronically prepared with single, bipolar electrodes in caudal midbrain central gray matter can be used in successive weeks to demonstrate to laboratory course students: sensory evoked potentials in anesthetized and unanesthetized preparations; self-stimulation and/or escape; and stimulationproduced analgesia to peripheral pain. The preparation and procedures are simple, and accuracy in electrode placement is enhanced by the proximity of this structure to stereotaxic zero. Using the same animal repetitively minimizes time spent in surgical preparation and post-surgical recovery. The central gray matter is a relatively unexplored region, and studying it can lead to original observations.

The effects of stimulating the midbrain central gray matter (CGM) on neuronal response in the ventroposteromedial (VPM) nucleus produced by stimulating tooth pulp, A-alpha and A-delta fibers of the intraorbital nerve and the caudal nucleus of the spinal trigeminal tract (CN STT) were investigated during experiments on cats under thiopental-chloralose anesthesia. It was found that applying trains of stimuli to the CGM produced excitatory responses in a proportion of the test neurons with latencies of up to 30 msec. Application of conditioning stimulus to the CGM led to suppression of response of efferent stimulation in neurons belonging to “low-threshold,” “convergent,” and “high-threshold” groups. Responses produced in 40% of neurons by stimulating tooth pulp and A-delta fibers of the suborbital nerve, as well as those evoked in 26.4% of thalamic VPM cells by stimulating A-alpha fibers of the suborbital nerve were completely suppressed. The inhibitory effect found when stimulating CGM on response in certain neurons, produced by stimulating both the peripheral nerve and the CN STT, would indicate that the CGM could exert an influence on the activity of thalamic VPM neurons directly.

Stimulating the midbrain central gray matter (CGM) with trains of 10–20 stimuli was found to inhibit response to electrical stimulation of infraorbital nerve and tooth pulp A-alpha and A-delta afferents at 100 msec intervals in 65% of the caudal trigeminal nucleus in neurons tested during experiments on cats under chloralose-Nembutal anesthesia. Response was inhibited most effectively in “convergent” neurons (activated by stimulating infraorbital nerve and tooth pulp A-alpha and A-delta afferents) to stimulating tooth pulp (0.76) and, to a somewhat lesser degree, to stimulation of A-alpha afferents (0.6). For “high-threshold” neurons (activated by stimulating infraorbital nerve and tooth pulp A-delta afferents), success rate of inhibiting response under the effects of CGM stimulating measured 0.71 and 0.48 for “low-threshold” cells (activated by stimulating infraorbital nerve A-alpha afferents). Stimulating CGM produced an excitatory response in 10 caudal trigeminal nucleus neurons within 7.5–20 msec; after this neurons showed no reaction to peripheral nerve stimulation for a 200–450 msec period. The possible involvement of these neurons in pressing the mouth-opening reflex produced by CGM stimulation is discussed in this article.

Electrical stimulation via electrodes implanted in the lateral hypothalamus may induce intraspecific aggressive behavior. Small electrolytic lesions placed via these electrodes resulted in a five– to tenfold increase in the current threshold for aggression. Degenerating fibers were stained by means of the Fink-Heimer method and could be followed caudally to the dorsal midbrain central gray and to the mammillary bodies. A few axons could be traced rostrally to the medial septum. Aggression could be induced from 10 of 112 electrodes implanted in the central gray; the other electrodes elicited either locomotion, vocalization, jump, or “alarm-like reactions.” The morphology of the induced aggression was similar to the morphology of the hypothalamically induced aggression, though it was often accompanied with motor disturbances and was less intense. Hypothalamic stimulation was combined with simultaneous central gray stimulation in rats with electrodes both in the hypothalamus and in the central gray. Hypothalamic thresholds for aggression could be lowered by this stimulation of the central gray, even when no aggressive responses were observed during central gray stimulation alone. This suggests that, although aggression is not manifest, electrical stimulation may activate neural tissue involved in aggressive behavior. It is concluded that in rats central gray and hypothalamus are part of the same neural network mediating intraspecific aggression.

Recent studies suggest that lesions to the globus pallidus, lateral thalamus, ventrolateral thalamus, parafascicular thalamus, substantia nigra, or midbrain central gray in adult rats are associated with a nonspecific (generalized) learning impairment. The present study showed that lesions to any one of the foregoing structures, except the ventrolateral and parafascicular thalamus, in 21-day-old rats likewise produce a generalized learning impairment, as evidenced by significant deficits on a white-black discrimination, a nonvisual 11-deg incline-plane discrimination, and a 3-cul maze. A possible brain-injured animal model of mental retardation is discussed.

Behavioral effects of electrical stimulation, mostly in or near the midbrain central gray, were studied as indicators of rewarding, aversive, arousing, and analgesic properties of the stimulation at 32 intracranial sites in rats. Stimulation-produced analgesia was demonstrated at sites which were randomly distributed regarding self-stimulation and escape effects in the same group of electrode placements. But stimulation at sufficient current strength to produce analgesia also typically elicited: arousal reactions; head, body, and locomotor movements; suppression of spontaneously occurring consummatory behaviors; and self-stimulation, if observed at a particular site. Thus, analgesic stimulation in this study was not free of widespread behavioral effects. Of general interest may be the finding that current threshold for arousal effects were significantly lower at escape sites than at self-stimulation sites.

Rats were trained to lever-press for intracranial self-stimulation (ICSS) with electrodes in the midbrain central gray area. The effects of naloxone (0.1–30.0 mg/kg, SC) on a continous reinforcement (CRF) schedule were determined. Rats were then re-trained on higher fixed-ratio (FR) schedules, and naloxone was re-tested at FR: 5, 10, 15 and 20. Only moderate reductions in lever-pressing rates were obtained at the highest dose of naloxone under CRF and FR: 5 schedules. In contrast, pronounced, dose-dependent reductions in ICSS rates occured at FR: 10, 15 and 20. The time-course for this reduction at FR: 20 was consistent with an opiate-antagonistic action of naloxone. The modest decrease in locomotor activity produced by naloxone in a matched group of control rats was not sufficient to account for the effects on ICSS. The threshold of naloxone for reducing the rate of ICSS lever-pressing was lowered by increasing the effort and/or time requirement for each reinforcement.

Cats, who had displayed escape or “fear”-like behavior by electrical stimulation of the midbrain central gray, were trained to interrupt the delivery of electrical stimulation of the midbrain central gray by plate pushing (switch-off behavior). After cats successfully learned to perform this switch-off behavior, they were further subjected avoidance conditioning trials in which neutral stimulus such as bell sound served as conditioned stimulus (CS), and electrical midbrain central gray stimulation as unconditioned stimulus (UCS). After cats reached the criterion of the avoidance learning, that is, appearance of the conditioned avoidance responses (CR) above 80%, then they were subjected extinction trials until they showed no CR. After that, they were given re-conditioning trials and extinction trials.Results are following : 1. Four cats out of seven succeeded in avoidance learning. Their stimulation sites were in the mid-paramedian position of the periaquedual gray matter (see Figs. 1 and 2).2. Two cats showed CR a little. One cat completely failed to show CR. Their stimulation points were in the basic and medial position of the midbrain central gray (see Figs. 1, 3, 4 and 5).These findings suggest differences between learning induced by intracranial stimulation and that induced by peripheral stimulation, and also differences between avoidance learning based on switch-off behavior induced by midbrain stimulation and that induced by hypothalamic stimulation.