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PubMed2000

Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome.

Rearing rats in isolation has been shown to be a relevant paradigm for studying early life stress and understanding the genesis of depression and related affective disorders. Recent studies from our laboratory point to the relevance of studying the social isolation syndrome as a function of home caging conditions. Accordingly, the present series of experiments assessed the contribution of each condition to the expression of the prepulse inhibition of the acoustic startle, food hoarding and spontaneous locomotor activity. In addition, ex vivo neurochemical changes in the brains of isolated and grouped rats reared either in sawdust-lined or in grid-floor cages were determined by measuring dopamine and serotonin as well as their major metabolites in a "psychosis circuit" that includes mainly the hippocampus and selected hippocampal efferent pathways projecting towards the anterior cingulate and infralimbic cortices, nucleus accumbens, dorsolateral caudate nucleus, amygdala and entorhinal cortex. The results of the present study demonstrate that rearing rats in isolation (i) produces a syndrome of generalized locomotor hyperactivity; (ii) increases the startle response; (iii) impairs prepulse inhibition; (iv) tends to increase food hoarding behavior; (v) increases basal dopamine turnover in the amygdaloid complex; (vi) decreases basal dopamine turnover in the infralimbic part of the medial prefrontal cortex; and (vii) decreases basal turnover of serotonin in the nucleus accumbens. In the entorhinal cortex, dopamine neurotransmission seemed to be more sensitive to the caging conditions since a decreased basal turnover of dopamine was observed in grid-reared animals. Plasma corticosterone levels were also increased in grid-reared animals compared with rats reared in sawdust cages. Finally, isolates reared on grids showed a significant positive correlation between plasma corticosterone levels and dopamine in the left nucleus accumbens.Altogether, these results support the contention that there is a link between social isolation, attention deficit, spontaneous locomotor hyperactivity and reduced dopamine turnover in the medial prefrontal cortex. Furthermore, our data demonstrate that rearing rats in grid-floor cages represents a form of chronic mild stress associated with increased corticosterone levels, decreased basal turnover of entorhinal dopamine and increased dopamine activity in the left nucleus accumbens. Finally, a significant and selective decrease in the basal turnover of serotonin in the nucleus accumbens of isolated rats may be linked to the isolation-induced locomotor hyperactivity.

Acoustic Stimulation↗
PubMed2002

Distinct pattern of c-fos mRNA expression after systemic and intra-accumbens amphetamine and MK-801.

Pharmacological manipulation of both dopamine and glutamate systems affects motor responses in laboratory animals. The two systems, however, seem to act in opposite ways, since direct or indirect activation of dopamine receptors induces similar stimulatory effects to those seen following blockade of N-methyl-D-aspartate receptors. In the present study we compared the pattern of c-fos activation induced by systemic and intra-accumbens administration of the non-competitive N-methyl-D-aspartate antagonist MK-801 and the indirect dopamine agonist amphetamine. Systemic MK-801 induced c-fos mRNA expression in the motor cortex and preferentially in the motor thalamus, i.e. ventrolateral nucleus. Systemic amphetamine, on the other hand, enhanced c-fos mRNA expression in the shell of the accumbens and in limbic thalamic nuclei such as the anteroventral and anterodorsal nuclei. The main effect observed after intra-accumbens administrations of either drug was enhanced c-fos expression in the thalamus, somewhat similar to what seen following systemic administration. In fact also in this case there was a preferential activation of the limbic thalamus by amphetamine and the motor thalamus by MK-801. The present results confirm that different neural substrates underlie behavioral effects induced by systemic administrations of N-methyl-D-aspartate receptor antagonists and dopamine agonists. Further they suggest that intra-accumbens manipulation of the two neural systems could affect different efferent pathways from this structure activating different thalamic targets.

Amphetamine↗
PubMed2001

Activation of the subfornical organ enhances extracellular noradrenaline concentrations in the hypothalamic paraventricular nucleus in the rat.

Experiments were carried out to investigate whether angiotensinergic efferent pathways from the subfornical organ (SFO) regulate the noradrenergic system in the region of the hypothalamic paraventricular nucleus (PVN). Intracerebral microdialysis techniques were utilized to quantify the extracellular content of noradrenaline (NA) in the PVN area. In urethane-anaesthetized male rats, electrical stimulation (5-20 Hz, 600 microA) of the SFO significantly increased the NA concentration in the region of the PVN, and the increase was significantly prevented by pretreatment with the angiotensin II (ANG II) antagonist saralasin (Sar, 5 microg), into the third ventricle (3V). Injections of ANG II (5 microg) into the 3V significantly enhanced NA release in the PVN area. These results suggest that the angiotensinergic pathways from the SFO to the PVN may act to enhance NA release in the region of the PVN.

Angiotensin II↗
PubMed2002

Vestibular-evoked myogenic potentials: a method to assess vestibulo-spinal conduction in multiple sclerosis patients.

Vestibular-evoked myogenic potentials (VEMPs), elicited by acoustic stimulation, have been proposed in the assessment of the vestibulo-cervical reflex pathways. The procedure has been previously validated in several otovestibular disorders. The aim of this study was to investigate patients affected by multiple sclerosis (MS) in the attempt to clarify the underlying physiopathogenetic mechanisms and the clinical utility of VEMPs in detecting vestibulospinal involvement in this disease. VEMPs were obtained according to the technique described by Colebatch and Halmagyi [Neurology 42 (1992) 1635]. We averaged the surface tonic electromyogram from right and left sternocleidomastoid muscle, after bilateral click stimulation (click duration 0.1 ms, repetition rate 3 Hz, intensity 140 dBSPL, 256 stimuli, repeated at least twice). In all cases, we obtained the biphasic, initially positive, p13-n23 wave pattern. P13 peak latency was bilaterally or unilaterally delayed in 8 out of 15 patients (mean delay: 2.2 ms; p < 0.01 on right and <0.05 on left side) and peak-to-peak amplitude significantly reduced (mean amplitude loss: 130 microV; p < 0.01 on right and <0.05 on left side). Their overall diagnostic yield resulted in 60%. In conclusion, the present findings prove that VEMPs are delayed in p13 component and altered in amplitude in MS patients. We hypothesise that these changes might be the result of a conduction impairment in vestibulo-spinal fibres, producing a morphologic alteration of the myogenic responses.

Acoustic Stimulation↗
PubMed1997

Behavioral regulation of gonadotropin-releasing hormone production.

In vertebrates reproductive readiness requires coordination between the sexes. Behavioral interactions with potential mates can initiate the neuroendocrine events that are required for successful copulation, ovulation, and fertilization. Regardless of the efferent pathway used, their targets are the neurons that produce and secrete gonadotropin-releasing hormone (GnRH). Several excellent animal models are currently under use to study the relationship between behavior and GnRH. In the musk shrew (Suncus murinus) starting 15 h after mating, prior to ovulation, GnRH-ir cell numbers are elevated along with GnRH content in brain and estradiol in plasma. Immunoreactive GnRH cell numbers also change in brains of female musk shrews sacrificed during, and directly after, brief interactions with males. These rapid changes in GnRH-ir cells are not correlated with measurable increases in GnRH content or elevations in plasma concentrations of estradiol. To determine which aspect(s) of the behavioral interaction is salient for the change in GnRH-ir, studies have been conducted in which interactions with males and their sensory cues were restricted during a 1-h interaction. In this study, behavioral interactions with an awake male behind a screen barrier resulted in a decrease in the numbers of GnRH-ir cells in the forebrain. Further studies with this animal model will help determine how behavioral inputs stimulate processing and release of GnRH.

Animals↗
PubMed1998

Responses of raphe nucleus projecting subfornical organ neurons to angiotensin II in rats.

The subfornical organ (SFO) is an important central site of action of circulating angiotensin II (ANG II). Although neuroanatomical tracing studies have identified the efferent pathways from the SFO to the midbrain raphe nucleus (RN), the functional role of the pathways is unknown. The present study was carried out to examine the responses of SFO neurons projecting to the dorsal RN (DRN) to microiontophoretic application or intracarotid injection of ANG II in male rats under urethane anesthesia. Twenty-three neurons in the SFO were antidromically identified by electrical stimulation of the midbrain DRN. Of these identified units, 13 were excited by ANG II applied iontophoretically, while 10 were unresponsive. ANG II-induced excitation was prevented by the ANG II antagonist saralasin (Sar) applied iontophoretically. The activity of seven out of 10 units that displayed this excitation to iontophoretically applied ANG II was also enhanced by intracarotid injection of ANG II. These results suggest that SFO neurons projecting to the DRN may monitor the circulating level of ANG II and carry the information to the DRN.

Angiotensin II↗
PubMed2000

Prevalence and ultrastructural morphology of axosomatic synapses on spiral ganglion cells in humans of different ages.

Axosomatic synapses were found on human spiral ganglion cells (HSGCs). Ultrastructural characterization and calculation of the prevalence of these synapses were performed by electron microscopic semi-serial sections of both type I and type II HSGCs, in specimens from subjects of ages 1 day, 14 days, 21 years and 51 years. Synapses on type I HSGCs were extremely rare. In contrast, axosomatic synapses were present on approximately 50% of type II HSGCs of a young adult. This prevalence seemed to vary by age. Thus, no synapses were found in a 1-day old neonate, few in a 14-day old, and on approximately 15% of the type II SGCs from a 51-year old specimen. The origin of the nerve fibers synapsing on the type II HSGCs could not be determined. In view of the fact that some of the fibers projected from the intraganglionic spiral bundle, which is known to contain olivocochlear efferents, these fibers may represent an efferent pathway to the spiral ganglion. However, since there was morphological evidence of more than one type of nerve fiber synapsing on type II HSGCs, other neural origins must be considered. Although the physiological function of these synapses is unknown, they may mediate pre-synaptic neural modulation of the type II HSGCs at the level of the spiral ganglion.

Adult↗
PubMed1998

Noise-induced threshold shift dynamics measured with distortion-product otoacoustic emissions and auditory evoked potentials in chinchillas with inner hair cell deficient cochleas.

Chinchillas (n = 6) were treated with carboplatin and, following a 30-day recovery period, were exposed to a 115 dB peak SPL impact noise presented at a rate of l/s for 6 h/day for 10 days. A second group (n = 6) received only the noise treatment. Cubic distortion product otoacoustic emissions (2f1-f2) and auditory evoked potential (AEP) detection thresholds in response to tone bursts were measured before and 30 days after drug treatment and following the first and 10th day of the noise exposure. Thirty days after the final exposure day, permanent changes in AEP detection thresholds and emissions were measured and cochleograms constructed. The drug treatment eliminated over 80% of the inner hair cells (IHC) in the cochlea, leaving the outer hair cell (OHC) population essentially intact prior to the interrupted noise exposure. The drug treatment alone had very little or no effect on AEP detection thresholds and emission metrics. Following the noise exposure, the IHC-deficient animals showed clear 'toughening' effects in the AEP and emission measures which were the same as measured in the group receiving only the noise. After a 30-day post-exposure recovery period. AEP thresholds were elevated about 10 dB at the low frequencies in the drug-noise group whereas emissions returned to near normal despite the massive IHC losses. These results are consistent with the idea that an intact OHC population is required for toughening. However, sound-evoked efferent pathways activated by the few remaining IHCs (approximately 20%) which, in this preparation, are distributed throughout the cochlea, may still contribute significantly to the toughening phenomena.

Animals↗
PubMed1986

Neural activities in the monkey basal ganglia related to attention, memory and anticipation.

Discharges of single neurons were recorded in the caudate nucleus of an awake monkey. The monkey was trained to perform a series of behavioral tasks which required him to fixate on a spot of light on a screen and if the spot jumped to another location to make a saccade to refixate it. A significant portion of the neurons in the head and body of the caudate nucleus showed increases in their activities in relation to the behavioral tasks. While some neurons responded to the visual stimulus (light spot), others showed activities preceding a saccade. Another group of neurons showed activities not directly related to such sensory or motor events but presumably related to monkey's cognitive states. Even the visual or saccade-related activities were highly dependent on the behavioral context in which a given visual stimulus was presented or a given saccade was elicited. This report presents typical examples of caudate neural activities related to selective attention, short-term memory and anticipation of future events, and explains how such complex signals in the caudate are converted to oculomotor outputs through a major efferent pathway of the basal ganglia, namely caudate--substantia nigra pars reticulate--superior colliculus.

Animals↗
PubMed1990

[Hypertonic sodium chloride and hemorrhagic shock].

Numerous experimental studies on the effects of hypertonic saline in haemorrhagic shock have been published and controlled clinical studies are now beginning to be reported. Animals suffering from an otherwise lethal haemorrhagic shock survived when given hypertonic sodium chloride solution (7.5%, 2,400 mosmol.1-1). In most studies, this solution was more efficient than isotonic fluids in treating controlled haemorrhage. Although the mechanisms involved are not yet fully understood, they certainly include the following: 1) plasma volume expansion due to osmotic fluid shifts into the vascular compartment from intra- and extra-cellular fluid reservoirs, as hypertonic saline induces hypernatraemia and hyperosmolarity, both effects linked to the sodium load; 2) non specific precapillary vasodilation of renal, coronary and splanchnic vessels; 3) arterial and venous vasoconstriction in muscle and skin, due to a vagal reflex set off by the lung osmoreceptors, the efferent pathway of which is likely to be the sympathetic nervous system; 4) increased myocardial contractility. Hypertonic saline also decreases intracranial pressure, and improves lung function during resuscitation of haemorrhagic shock. However, hypertonic saline should not yet be used routinely in man, except in controlled clinical studies. Indeed, there are as yet not enough data concerning humans. Moreover, during uncontrolled haemorrhage, hypertonic saline increased blood pressure, and therefore bleeding, thus reducing survival rates. Further clinical studies are required before hypertonic saline could be safely recommended for treatment of haemorrhagic shock.

Animals↗
PubMed2003

Contribution of the adrenal glands and splenic nerve to LPS-induced splenic cytokine production in the rat.

Both the hypothalamic pituitary adrenal axis (HPAA) and the sympathetic nervous system (SNS) can inhibit immune function and are regarded as the primary efferent pathways for neural-immune interactions. To determine if this relationship is maintained in vivo in response to an inflammatory stimulus, rats were injected intravenously (iv) with various doses of lipopolysaccharide (LPS) and splenic cytokine mRNA and protein levels were measured at several dose and time intervals post-injection. The spleen was chosen as the target organ because both the neural and hormonal inputs to the spleen can be selectively removed by splenic nerve cut (SNC) and adrenalectomy (ADX), respectively. Data from our dose response studies established that maximum levels of splenic cytokines were induced in response to relatively low doses of LPS. Minimal changes in LPS-induced splenic cytokine levels were observed in response to ADX, SNC, or a combination of the two procedures across several doses of LPS. These results suggest that there are aspects of immune regulation that are functionally removed from these central modulatory systems and that the counter-regulatory responses induced by LPS have minimal impact on the concurrent induction of cytokines by this inflammatory stimulus. The conceptual model of neural-immune regulation as an inhibitory feedback system, at least with regards to the early activational effects induced by an inflammatory stimulus, was not supported by these studies.

Adrenal Glands↗
PubMed2002

The superior olivary complex of the hamster has multiple periods of cholinergic neuron development.

Cholinergic neurons of the superior olivary complex share a common embryological and phylogenetic origin with brainstem motor neurons and serve as the major descending efferent pathway either to the cochlea as part of the olivocochlear system or to the cochlear nucleus. In this study, we investigated the developmental expression patterns of choline acetyltransferase (ChAT) and its co-localization with calcitonin gene-related peptide within the superior olivary complex and neighboring brainstem motor nuclei. At embryonic day 12, neurons in the ventral nucleus of the trapezoid body were first to express ChAT. The temporal expression pattern of both ChAT mRNA and immunoreactivity in this periolivary region mimicked motor neurons in the facial and trigeminal motor nuclei. Just before birth, shell neurons surrounding the lateral superior olive expressed ChAT. Neither ChAT-positive periolivary neurons nor shell neurons co-expressed calcitonin gene-related peptide during development or in the adult. Immediately following birth, intrinsic neurons within the lateral superior olive expressed ChAT but not calcitonin gene-related peptide. However, a transient increase in the number of ChAT-positive neurons in the lateral superior olive coincided with the onset of the calcitonin gene-related peptide co-expression within these neurons. We conclude that ChAT expression appears first in periolivary regions containing medial olivocochlear neurons, precedes the expression of calcitonin gene-related peptide in the superior olivary complex, and is co-expressed with calcitonin gene-related peptide within the lateral superior olive containing lateral olivocochlear neurons. These data suggest that the lateral olivocochlear system co-expresses ChAT and calcitonin gene-related peptide, whereas the medial olivocochlear system does not.

Animals↗
PubMed1989

Control of blood and extracellular volume.

Blood and extracellular fluid volume are maintained within narrow limits despite considerable daily variations in the intake in salt and water. As summarized schematically in Figure 15, the urinary excretion of salt and water responds to changes in blood volume and arterial pressure. Volume-sensitive receptors located predominantly in the cardiac atria and arterial tree sense acute changes in the filling of the blood volume compartment, and urinary sodium excretion is adjusted in response to these detector mechanisms by virtue of alterations in both glomerular filtration rate and tubular sodium reabsorption. The reabsorption of sodium by the tubule responds to changes in extracellular fluid volume as well as to changes in filtered sodium load. Glomerular filtration rate and tubular reabsorption of sodium are influenced importantly by physical properties of the plasma in glomerular and peritubular capillaries and by the composition of the tubular fluid. The renal arterial perfusion pressure is a major factor regulating tubular reabsorption of sodium and water as signalled via changes in renal interstitial hydrostatic fluid pressure. Renal nerves and a variety of systemic and local hormones also influence tubular reabsorption of sodium and water directly by effects on transepithelial sodium transport and/or indirectly by altering renal medullary haemodynamics and the pressure-natriuresis-diuresis relationships. Thus, utilizing a variety of overlapping effector mechanisms that influence renal sodium and water excretion, mammalian organisms have achieved a high degree of stability of body fluid volumes. The fundamental relationship between arterial pressure and renal excretion appears to be the major mechanism which provides for the long-term control of body fluid volume. The sensitivity of the pressure-natriuresis-diuresis relationship is modified by the efferent pathways of the rapid-acting reflex and mechanoreceptor detectors of volume. Working together, these mechanisms provide a remarkable degree of rapid and long-term extracellular and blood volume stability.

Animals↗
PubMed1992

Perineal motor potentials to magnetic stimulation, pudendal evoked potentials and perineal reflex in women.

Motor potentials to transcranial and lumbar magnetic stimulation were recorded from the perineum in 14 healthy women. The response to transcranial stimulation presented an onset at 20.2 +/- 1.3 ms and a negative peak at 25.1 +/- 1.9 ms. Lumbar responses presented an onset at 5.1 +/- 0.8 ms, and the motor central conduction time measured 14.4 +/- 1.5 ms. Perineal reflex, cortical and lumbar pudendal evoked potentials were recorded after electrical stimulation of the labia minora. These tests are of possible clinical use in the evaluation of sphincter disturbances as they investigate the afferent and efferent pathways concerning pudendal nerve function.

Adult↗
PubMed1995

Cascade of metastatic colorectal carcinoma from the liver to the anterior diaphragmatic lymph nodes.

RATIONALE AND OBJECTIVES: Metastases of colon carcinoma from the liver to porta hepatis and celiac axis lymph nodes constitute a contraindication to hepatic metastatic resection. Our objective was to determine the frequency of anterior diaphragmatic lymph node (ADLN) enlargement, another efferent pathway of hepatic lymphatic drainage, in patients with colon carcinoma. METHODS: Abdominal computed tomography scans from 50 patients with colon carcinoma in whom hepatic metastases were either present (n = 25) or absent (n = 25) were reviewed. ADLNs greater than or equal to 5 mm were considered enlarged. RESULTS: Thirteen of 25 patients with hepatic metastases had ADLNs greater than or equal to 5 mm; three of 25 patients without hepatic metastases had ADLNs greater than or equal to 5 mm. The difference was statistically significant (p = .002). CONCLUSION: Metastases of colon carcinoma from the liver to the ADLNs probably are not rare. ADLN involvement would obviate hepatic resection. The ADLNs should be assessed preoperatively in surgical candidates with hepatic metastases of colon carcinoma.

Adult↗
PubMed1997

Elicitation, modification, and conditioning of the rabbit nictitating membrane response by electrical stimulation in the spinal trigeminal nucleus, inferior olive, interpositus nucleus, and red nucleus.

Elicitation of responses by electrical brain stimulation (EBS) was related to the synaptic distance of the target nucleus from the accessory abducens. Specifically, responses to EBS in the spinal trigeminal nucleus (TRIG) and red nucleus (RN) increased as a positive function of stimulation parameters. Responding to EBS in the interpositus nucleus (IP) was lower, and responding to EBS in the inferior olive (IO) was negligible. EBS in the TRIG, IP, and RN nuclei was then paired with a tone conditioned stimulus (CS). The CS modified responses for EBS in RN and TRIG but not IP. CS-EBS pairings yielded conditioned response (CR) acquisition, in which Groups TRIG, IP, and RN reached asymptotes of 90%, 70%, and 43% CRs, respectively. Thus, contrary to previous findings, EBS in the efferent pathway can support CR acquisition. The results are discussed with respect to the role of projections from the RN to the cerebellar cortex and the TRIG nucleus.

Abducens Nerve↗
PubMed1980

Host genotype influences immunomodulation by interferon.

Interferon influences both afferent and efferent pathways of delayed-type hypersensitivity (DH) in the mouse. In animals previously sensitised to picryl chloride, sheep red blood cells (SRBC) or Newcastle disease virus (NDV), and treated with interferon just before challenge with any of these antigens, the antigen-elicited reaction, as measured by the ear-swelling (picryl chloride) or footpad swelling (SRBC and NDV) test, is either decreased or completely inhibited, depending on the dose of interferon administered. In addition to this action on expression of the sensitised state, interferon decreases or inhibits sensitisation to SRBC or NDV when administered 24 h before immunisation. These effects were recently confirmed using electrophoretically pure mouse interferon, thus ruling out the possibility that they are caused by other proteins present in the previously used partially purified interferon preparations. For the effect on sensitisation, the timing of interferon administration is crucial, and when interferon is administered a few hours after the antigen, sensitisation can actually be enhanced, as reported here; the enhancement of sensitisation by interferon is influenced by the dose of antigen and by the genotype of the mice that are sensitised.

Animals↗