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PubMed1990

A comparison of preparation-related neuronal activity changes in the prefrontal, premotor, primary motor and posterior parietal areas of the monkey cortex: preliminary results.

Single-unit activity of prefrontal (PF), premotor (PM), primary motor (MI) and posterior parietal (PP) cortical areas was analysed from 3 monkeys trained to perform visually guided arm movements in a between-arms choice reaction time (RT) task. Percentages of preparation-related units, i.e. units whose change in activity during the preparatory period was correlated with RT, were 19% in PF, 31% in MI, 46% in PM and 68% in PP, respectively. These data support the hypothesis that neural pathways connecting PP association areas to MI, via PM, are involved mainly in movement planning.

Animals↗

PubMed1994

Intracranial action of corticosterone facilitates the development of behavioral inhibition in the adrenalectomized preweanling rat.

We tested the hypothesis that in preweanling rats central administration of exogenous corticosterone (CORT) is sufficient to facilitate the development of behavioral inhibition. 28-gauge cannulae containing varying concentrations of CORT (0, 25, 50 and 100%) were implanted unilaterally into the lateral ventricles of 9-day-old rat pups. After a 24-h postoperative recovery period, pups were adrenalectomized. At 14 days of age, pups were tested for behavioral inhibition which consisted of removing the pup from the nest and exposing it to an unfamiliar adult male rat. Pups implanted with cannulae containing 0, 25 and 50% concentrations of CORT spent significantly less time in freezing postures than pups implanted with cannulae containing 100% CORT. These freezing pups also tended to emit fewer ultrasonic vocalizations than pups in the other three implant conditions, albeit the level obtained was not statistically significant. RIAs indicated that, in general, hormone-filled cannulae produced no detectable concentrations of plasma CORT on the day of the test or on days preceding testing. Results suggest that in the early postnatal period endogenous CORT acts centrally to facilitate the development of neural pathways involved in the ontogenetic expression of behavioral inhibition.

Adrenalectomy↗

PubMed1996

Stimulation of the medial preoptic area of the hypothalamus in the rat elicits increases in intracavernous pressure.

Penile erection can be elicited by various stimuli integrated in the spinal cord and/or higher central nervous structures. The medial preoptic area (MPOA) of the hypothalamus is known to play a key role in the regulation of the male sexual behavior. In anesthetized male rats we performed MPOA stimulation via stereotaxically implanted electrodes or canulae delivering L-glutamate. An erectile response, assessed by an increase of intracavernous pressure (ICP), was recorded during electrical stimulation of the MPOA. Stimulating the posterior region of the MPOA elicited a greater erectile response than stimulation applied to the anterior region. Microinjections of L-glutamate also elicited an ICP increase. Stimulation of MPOA neurons therefore elicits activation of neural pathways controlling penile erection.

Analysis of Variance↗

PubMed1983

Bombesin-like immunoreactivity in sympathetic ganglia.

Nerve fibres showing immunoreactivity for bombesin have been observed in prevertebral sympathetic ganglia of the rat and guinea-pig. The distribution of bombesin immunoreactive fibres was compared with the distribution of the structurally-related peptide substance P. Dense networks of varicose bombesin immunoreactive fibres were observed, and in the rat coeliac ganglion the density exceeded that of the substance P immunoreactive fibres. Extracts of rat and guinea-pig coeliac ganglion contained material cross-reacting in radioimmunoassays for bombesin tetradecapeptide. Similar concentrations of bombesin and substance P were found in the guinea-pig ganglion, whereas in the rat the concentration of bombesin was about 20 times as high as that of substance P. Two molecular forms of immunoreactive bombesin were identified, neither of which corresponded exactly to synthetic bombesin. The two components were also distinguishable from synthetic substance P. A potential role of a bombesin-like peptide in neural pathways between the gut and prevertebral ganglia is suggested.

Animals↗

PubMed1984

Spinal substance P transmits bradykinin but not osmotic stimuli from hepatic portal vein to hypothalamus in rat.

Peripheral osmo - and bradykinin-sensitive receptors which have been previously localised within the hepatic portal vein area, activate the hypothalamo-neuro-hypophysial system through a neural pathway projecting to the lower thoracic spinal cord. In this paper we attempted to identify the spinal transmitter(s) involved and to answer the question whether osmoreceptors are in fact chemosensitive nociceptors. The portal vein of anesthetised rats was superfused with 0.2 ml of 4% NaCl or 1 microM bradykinin, and hypothalamo-neurohypophysial responses were measured either electrophysiologically or by radioimmunoassay of arginine vasopressin. Responses to bradykinin, but not to hypertonic saline, were abolished in rats pretreated 2 wks previously with capsaicin s.c., and immunocytochemistry for substance P in these animals showed that substance P was strongly depleted both in the dorsal thoracic spinal cord and in the portal vein. The spinal injection of 8 microliter 0.1 mM capsaicin at T8-T9 elicited a pronounced hypothalamo-neurohypophysial response, and diminished reversibly the response to bradykinin superfusion of the portal vein. Spinal capsaicin had no effect on responses to hypertonic saline. Similarly, the spinal (T8-T9) injection of 8 micrograms substance P antagonist, the [D-Pro4, D- Trp7 ,9,10, Val8 ]substance P (4-11), reduced reversibly the responses to bradykinin by about 50% without affecting those to hypertonic saline. The spinal injection of 8 micrograms substance P, at the same site where substance P antagonist was applied, elicited within 4 s a prolonged response (several min). A slightly longer delay between stimulus and neurophysiological response was observed for spinal capsaicin and for bradykinin superfusion. Responses to hypertonic saline superfusion of the portal vein, however, occurred within 1-2 s. The results show that portal vein osmoreceptors are distinct from chemo-sensitive nociceptors, and suggest that substance P may be a spinal mediator for chemo-sensitive portal vein nociceptors. The spinal transmitter for osmosensitive afferents, and the physiological importance of the portal vein area in chemosensation remain to be established.

Animals↗

PubMed1987

A stain for ischaemic or excessively stimulated neurons.

Loyez' myelin stain sometimes impregnates the perikarya and processes of neurons. This is rare in normal adult mice, but can be provoked by various means including electrical stimulation and mild ischaemia shortly before fixation. Passing a direct current or a train of pulses across the dura of the cerebral cortex produces a patch at the site of stimulation in which the neurons, but not the glia, are Loyez-impregnated; pulse-trains evoke such impregnation even at remote sites, presumably through orthodromic and/or antidromic activation. The strength and duration of stimulation necessary to provoke impregnation are below the threshold for causing an overt lesion. Local ischaemia produced by irreversibly occluding a small subarachnoid artery for as little as 7 min evokes a small patch of impregnated neurons in the superficial layers adjacent to the occluded artery. After slightly longer-lasting (e.g. 17 min) ischaemia, the impregnated zone spans most of the cortical depth. Mild global ischaemia produced by irreversibly occluding one or both common carotid arteries 30 min before fixation causes large numbers of neurons to be impregnated in many parts of the brain. That interventions as different as electrical stimulation and arterial occlusion both lead to neuronal impregnation may most plausibly be explained by the fact that they both cause cells to be depolarized. The method will be useful for visualizing overstimulated or ischaemic neurons, and may be applicable to the tracing of neural pathways.

Animals↗

PubMed1988

The patterns of [14C]2-deoxyglucose uptake in female rat brain produced by electrical stimulation of hypothalamic and limbic brain areas.

The aim of this study was to investigate the pattern of [14C]2-deoxyglucose uptake in anaesthetized rat brain produced by electrical stimulation of brain areas implicated, by previous electrical stimulation studies, in the neural control of pituitary hormone and especially gonadotrophin secretion. Stimulation of the median eminence led to a significant increase in the relative metabolic activities of the arcuate, ventromedial hypothalamic, supraoptic and paraventricular nuclei and the preoptic area. Stimulation of the suprachiasmatic or paraventricular nuclei or the medial preoptic area, anterior hypothalamic area, the dorsal or ventral hippocampus or amygdala led to an increase in the relative metabolic activity of many brain regions known to have direct connections with these areas, but in addition produced increases in the relative metabolic activity of areas which have secondary connections. Hippocampal stimulation confirmed previous neuroanatomical findings of major intrinsic functional connections between different fields of the ipsilateral and contralateral hippocampus. Stimulation of the amygdala, unexpectedly, did not change the relative metabolic activity of the arcuate nucleus and medial preoptic area which have neuroanatomical connections with the amygdala. Similarly, stimulation of the medial preoptic area did not change significantly the relative metabolic activity of the mamillary body and dorsomedial thalamic area. The effect of preoptic area stimulation on the relative metabolic activity of several brain regions was changed by ovariectomy and by injection of oestradiol benzoate. Stimulation of the preoptic area and suprachiasmatic nuclei, but not the anterior hypothalamic area or other brain regions, increased significantly the plasma concentrations of luteinizing hormone. These results show that (i) electrical stimulation of brain areas concerned with the control of gonadotrophin and other pituitary hormone secretion changes the metabolic activity of nuclei and neural pathways extrinsic as well as intrinsic to the hypothalamic-pituitary system, (ii) the [14C]2-deoxyglucose method can detect changes in antidromic as well as orthodromic activity and in multi-synaptic pathways, (iii) neuroanatomical pathways are not always activated metabolically by electrical stimulation, and (iv) the preoptic-suprachiasmatic nucleus gonadotrophin control system is discrete and is little affected by increased metabolic activity of the hypothalamus produced by stimulation of the anterior hypothalamic area or other brain areas.

Animals↗

PubMed1989

Developmental and regeneration-associated regulation of the limbic system associated membrane protein in explant cultures of the rat brain.

In the present study we have examined the topographic and temporal patterns of expression of the limbic system associated membrane protein by light and electron microscopic immunocytochemistry in organotypic cultures of the rat brain. The regional, cellular and subcellular distribution of staining in young cultures was similar to that in the intact brain of corresponding age. Since the tissue in vitro is isolated both from afferents and targets, short-term protein expression appears to be regulated by factors intrinsic to the neuron. In culture, the protein was present on the surface of neurons which are physiologically interconnected, such as neurons belonging to the septohippocampal system (cholinergic neurons in the septum and pyramidal and granule cells in the hippocampus). It was also present on the surface of axons and growth cones during process outgrowth. Thus, the limbic system associated membrane protein is expressed in an appropriate spatial and temporal pattern for mediating interactions between growing axons and their targets. The expression of the protein in culture showed some important differences as compared to the intact brain. With increasing age, there was an increasing scattering and disappearance of immunoreactivity in cultures fixed with paraformaldehyde/glutaraldehyde. The decreased immunoreactivity in aged cultures does not appear to reflect decreased protein synthesis, because unfixed and acetone-fixed explants continued to show immunostaining. Furthermore, dot-blot assays showed similar amounts of immunoreactivity in culture as in the intact brain of corresponding age. Thus, the age-dependent decrease of immunoreactivity may reflect altered insertion of the protein into the membrane or a modification of the epitope recognized by the antibody. There was a rapid increase (within 1 hour) of immunostaining on the surface of sprouting processes following mechanical lesion of mature, unstained axons. The altered distribution after tissue injury could be a means of ensuring specificity of connectivity during nerve fiber regeneration. On the basis of the reported findings, we suggest that system-specific membrane proteins, including the limbic system associated membrane protein, may mediate the formation of specific connections in the brain. Furthermore, we suggest that the reinnervation processes taking place after central nervous system injury may exhibit a similar molecular basis to the development of neural pathways.

Animals↗

PubMed1990

Differential target dependence in the developing brain: implications for mental retardation.

During development of the brain, many neurons exhibit a dependence on other neuronal populations for their survival and differentiation (target dependence). Evidence suggests that some neural pathways are much more dependent on single target neuronal populations for their survival than are others (differential target dependence). This phenomenon has important implications both for animal models of congenital human brain damage and for ideas concerning the aetiology of behavioural abnormalities associated with human mental retardation. Predictions of the neuronal deficits likely to arise from exposure to cytotoxic agents (e.g. ionizing radiation, hyperthermia, viral infection) at a particular time must take differential target dependence into account. It is known that target dependence affects corticopetal pathways involved with the discriminative senses (e.g. vision), more than monoaminergic and cholinergic corticopetal pathways which are believed to be involved with arousal, selective sensory attention, sleep, memory and cortical vasomotor function. Following prenatal damage to superficial layers of the cerebral cortex, this effect of differential target dependence leads not only to a relative hyperinnervation of the cortex with monoaminergic and cholinergic projections, but a specific deficit in visual pathways. The implications of this combined deficit for the behaviour and rehabilitation of the mentally retarded are considered.

Animals↗

PubMed1990

Infantile autism and Wernicke's encephalopathy.

In this paper I discuss evidence that brain damage in infantile autism may involve the same complex of brainstem nuclei that are damaged by alcohol abuse, thiamine deficiency, and asphyxia. These are metabolically the most active structures in the brain, which makes them vulnerable to many injurious factors. It is my belief that the high metabolic rate in the brainstem nuclei could support a control function for multiplexing of neural pathways, and that if this control is lost it may result in the defects of awareness and responsiveness seen in autistic children.

Asphyxia Neonatorum↗

PubMed1994

Prolactin in winter depression.

Women with winter depression have low serum prolactin concentration that is independent of both season and efficient bright light treatment administered in winter. A defect of neural pathways afferent to the paraventricular nucleus may explain these findings. Estrogen is thought to play a key role in modulation of the rhythmic responses in winter depression.

Afferent Pathways↗

PubMed1983

A simpler retractable wire knife.

A detailed description is presented for the construction of a simple and inexpensive retractable wire knife and holder/adjuster for stereotaxically placed transections of neural pathways. The accuracy and reliability of the knife are supported by experimental data demonstrating the ability of bilateral parasagittal hypothalamic knife cuts to induce excessive food intake and body weight gain in female rats.

Animals↗

PubMed1990

Taste responses in the parabrachial pons of ovariectomized rats.

Since the early 1970s it has been known that female rats prefer higher concentrations of sweet stimuli compared with males. Recent data have revealed that electrophysiological responses to sweet tastes recorded in the parabrachial nucleus of the pons (PbN), the second relay in the neural pathway for taste, are larger in diestrus female rats compared with those in males. Because it has been shown that ovariectomized rats have lowered preferences for saccharin compared with intact females, it is possible to predict that responses to sweet stimuli in the PbN of ovariectomized rats might be smaller than those in intact females. To investigate this hypothesis, electrophysiological responses to representatives of the 4 basic taste qualities, i.e., salty, sour, sweet and bitter, were recorded in the PbN of ovariectomized rats. Gustatory stimuli included NaCl (0.1 M), HCl (0.01 M), sucrose (0.5 M), quinineHCl (0.01 M) and Na-saccharin (0.004 M). Comparison of taste responses of 49 PbN units in ovariectomized rats with those in the PbN of intact female and male rats showed that responses to sweet stimuli were of comparable magnitude to those in female rats but elevated compared with those in male rats. However, responses of PbN units to quinine appeared to be larger in ovariectomized rats compared with those in the PbN of both intact female and male rats. These results suggest that decreased saccharin preference in ovariectomized rats may reflect a greater sensitivity to the bitter components of the taste of saccharin. Moreover, these data provide evidence that taste responses in the PbN are influenced by both the activational and organizational actions of ovarian hormones.

Animals↗

PubMed1993

NPY and galanin in a hibernator: hypothalamic gene expression and effects on feeding.

Neuropeptides such as neuropeptide Y (NPY) and galanin may play a role in regulating the pronounced seasonal changes in food intake shown by golden-mantled ground squirrels (Spermophilus saturatus). We used in situ hybridization histochemistry to localize the expression of NPY and galanin mRNA in the hypothalamus of normally feeding animals. NPY mRNA was abundantly expressed in the arcuate nucleus, while galanin mRNA was concentrated in both the arcuate nucleus and the dorsomedial nuclei. When NPY (0.1, 0.5, 2, and 8 micrograms) or galanin (0.1, 0.5, 2, and 8 micrograms) were injected into the third cerebral ventricle, food intake was significantly and dose-dependently increased over the subsequent 30 min. NPY stimulated significant increases in food intake for up to 2 h whereas galanin's effect did not extend beyond 30 min. Our results suggest that hibernating and nonhibernating rodents share common neural substrates for the regulation of food intake. Seasonal modulation of these neural pathways may contribute to annual cycles of food intake in hibernating mammals.

Analysis of Variance↗

PubMed1994

Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain.

We and others have reported that c-fos protein is induced in the hypothalamus and brain stem of the rat following central and peripheral injections of endotoxin (lipopolysaccharide; LPS). We have now examined possible mechanisms through which LPS induces c-fos protein. The cyclooxygenase inhibitor indomethacin and the glutamate NMDA antagonist MK801 inhibited c-fos protein in the paraventricular nucleus (PVN), supraoptic nucleus (SON), and the A1/A2 regions of the brain stem induced by IP or IV injections of LPS (40 micrograms). The H1 histamine antagonist diphenhydramine, but not the H2 histamine antagonist cimetidine, reduced the amount of c-fos labeling. MK801 also attenuated the effects of stress (foot shock) on c-fos protein; however, indomethacin had no effect on c-fos protein induced by stress. We next examined the importance of visceral afferent innervation on the response to LPS or stress. Subdiaphragmatic vagotomy completely blocked the induction of c-fos protein following IP injections of LPS; however, vagotomy had a minimal effect on c-fos protein induced in the PVN and SON following IV injections of LPS, but potentiated c-fos induction following foot shock. Thus, prostaglandin synthesis, glutamate release, histamine receptors, and visceral afferents represent functional biochemical and neural pathways through which endotoxin activates c-fos protein in specific autonomic and neuroendocrine regulatory nuclei. Activation of NMDA glutamate receptors may represent a final common pathway for the induction of c-fos protein in the brain induced by both endotoxin and stress.

Animals↗

PubMed1992

Estrogen influences auditory brainstem responses during the normal menstrual cycle.

We evaluated the impact of the menstrual cycle on auditory brainstem response (ABR) latency in nine normally cycling women. Subjects (age 23-40 years) using no hormonal therapy were recruited and underwent ABR testing during four different phases of the same menstrual cycle: early follicular (cycle days 1 to 3); mid-cycle (cycle days 12 to 15); mid-luteal (cycle days 17 to 22), and premenstrual (cycle days 25-27). Cycles were verified by basal body temperature, and serum estrogen (E2), progesterone (P), and gonadotropin levels. A control group of nine women (age 23-40 years) on oral contraceptives (Nordette-28) was also studied four times during a pill cycle. Results show a significant increase in the latency of wave III and wave V peak latencies and in the I-V interpeak interval associated with a high estrogen state at the mid-cycle phase. No statistically significant variations in latency were found in the birth control pill group. These data suggest the existence of brainstem auditory neural pathways that are sensitive to fluctuations in E2 levels during the menstrual cycle.

Adult↗

PubMed1992

Contributions of medial geniculate body subdivisions to the middle latency response.

Ongoing studies in our laboratory, concerned with identifying the neural pathways responsible for the auditory middle latency response (MLR), have involved analysis of surface and intracranial potentials following pharmacologic inactivation (with lidocaine) of small regions in the guinea pig brain. Previous studies indicate that MLR surface waves recorded over the temporal lobe originate from pathways anatomically distinct from those that generate MLR waves recorded over the midline. The medial geniculate body (MG) contributes to both MLR responses. At issue here are the relative contributions of ventral and caudomedial subdivisions, which have been linked to primary and non-primary auditory pathways, respectively. Ventral and caudomedial subdivisions contributed to the surface-recorded MLR in a distinctive manner. Lidocaine injections to both areas reduced the amplitude of the surface temporal response. Caudomedial injections had a much greater effect on the surface midline responses than did injections in the ventral portion. Thus, the ventral division, a part of the primary auditory pathway, contributes chiefly to the temporal response. The caudomedial portion, which may be linked to non-primary auditory pathways, contributes to both responses.

Acoustic Stimulation↗

PubMed1992

Relation between stimulation site of cardiac afferent nerves by adenosine and distribution of cardiac pain: results of a study in patients with stable angina.

OBJECTIVES: The purpose of this study was to establish whether stimulation of cardiac sensory receptors in different myocardial regions results in different distributions of cardiac pain. BACKGROUND: Previous studies have shown that adenosine provokes cardiac pain through stimulation of sensory receptors in the absence of myocardial ischemia. In this study adenosine was used to obtain a regional stimulation of cardiac sensory receptors. METHODS: Increasing doses of adenosine (0.25, 0.5 and 1 mg/min) were selectively infused into the right and then into the left coronary artery in 26 patients with stable angina. RESULTS: No patient developed ischemic electrocardiographic changes during either adenosine infusion. Eighteen patients experienced cardiac pain during both infusions. Despite the stimulation of sensory receptors in different myocardial regions, 13 patients experienced cardiac pain in the same body area. Adenosine-induced pain was always similar to the anginal pain. By contrast, the remaining five patients experienced adenosine-induced cardiac pain in different body areas. In two of these patients, the distribution of anginal pain was similar to that experienced during one of the two adenosine infusions. In the remaining three patients, the distribution of anginal pain was similar to that experienced during adenosine infusion into the right coronary artery during some anginal episodes and to that experienced during adenosine infusion into the left coronary artery during other episodes. CONCLUSIONS: During stimulation by adenosine of sensory receptors in different myocardial regions, the majority of patients experience cardiac pain in the same body area; only a few experience pain in different areas. These differences might be caused by different organizations of the ascending neural pathways to the cortex. Our results suggest that in the same patient different distributions of pain during anginal attacks are probably due to ischemia in different myocardial regions.

Adenosine↗