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PubMed1990

Lesion of the anteroventral third ventricle region abolishes the beneficial effects of hypertonic saline on hemorrhagic shock in rats.

The effect of intravenous infusion of hypertonic saline (HS, 7.5% NaCl) on the recovery of mean arterial pressure (MAP) during hemorrhage was studied in sham-operated rats and in rats with electrolytic lesion in the anteroventral third ventricle (AV3V) region. After intravenous infusion of 7.5% NaCl (4 ml/kg b.wt.), MAP increased from about 60 to 90 mmHg in sham rats and became stable at this level during all the time of observation (30 min). In AV3V-lesioned rats, after the same infusion, the MAP increased to 80 mmHg, but returned to the pre-infusion levels within 30 min. These results show that the integrity of the AV3V region is important for the beneficial effect of HS during hemorrhagic shock in rats. The AV3V lesion disrupts neural pathways involved in the maintenance of fluid balance and these changes probably abolish the effect of hypertonic saline.

Animals↗

PubMed1991

Projections from the subfornical organ to the supraoptic nucleus in the rat: ultrastructural identification of an interposed synapse in the median preoptic nucleus using a combination of neuronal tracers.

The subfornical organ, along with other regions of the lamina terminalis, may contain osmoreceptors and is likely to be a site of action of blood-borne angiotensin II. The neural pathways by which these stimuli lead to vasopressin secretion, have been suggested to extend from the subfornical organ to hypothalamic sites of vasopressin production either directly or via synapses in an intervening nucleus such as the median preoptic nucleus. In the present study, cholera toxin conjugated to horseradish peroxidase (CT/HRP) or colloidal gold (CT/Au) has been injected, respectively, into the subfornical organ and supraoptic nucleus of the same animal. The anterograde and retrograde transport of the toxin from these two sites has made possible the identification, at the ultrastructural level, of a synapse in the median preoptic nucleus interposed in the pathway between the subfornical organ and the supraoptic nucleus. Moreover, the presence of retrogradely transported CT/HRP and CT/Au in the same neurone in the median preoptic nucleus indicates that some neurones in this nucleus have axons with collateral branches to both the subfornical organ and supraoptic nucleus. Either or both of these pathways may transmit information related to the tonicity of the blood or circulating levels of angiotensin II to sites in the hypothalamus.

Animals↗

PubMed1991

Carbon filament implants promote axonal growth across the transected rat spinal cord.

Significant regeneration of neural pathways following complete transection of the spinal cord has yet to be demonstrated. In the present study, we analyzed the ability of carbon filaments to function as a scaffold for the regrowth of injured axons in the rat spinal cord. Through the use of three different axonal tracing methods, severed spinal axons were observed growing on and between carbon filaments implanted into the completely transected rat spinal cord. Carbon filaments, by providing a favorable adhesive surface and also a possible guiding function, may prove useful in the treatment of spinal cord injury.

Animals↗

PubMed1992

A species-specific population of tyrosine hydroxylase-immunoreactive neurons in the medial amygdaloid nucleus of the Syrian hamster.

The medial amygdaloid nucleus (Me) is part of a neural pathway that regulates sexual behavior in the male Syrian hamster. To characterize the neurochemical content of neurons in this nucleus, brains from colchicine-treated adult male and female hamsters were immunocytochemically labeled using antibodies that recognize the catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT), as well as dopamine. A large population of TH-immunoreactive (TH-IR) neurons was observed throughout Me of male and female hamsters, primarily concentrated in the midrostral and caudal portions of the nucleus. The somata were generally small to medium in size and bipolar. Brains from animals that did not receive colchicine contained a limited number of TH-IR neurons in Me as reported previously. The DBH and PNMT antisera did not label any cells in Me of colchicine-treated animals, and the dopamine antiserum labeled neurons in the same location as the caudal group of TH-IR cells. Therefore, these caudal TH-IR neurons are interpreted to be dopaminergic. The rostral group of TH-IR neurons, on the other hand, may be producing only the immediate precursor of dopamine, L-3,4-dihydroxyphenylalanine (L-DOPA). The TH-synthesizing neurons in Me of the Syrian hamster appear to be a species-specific group of cells located outside of the previously described catecholaminergic cell groups.

Amygdala↗

PubMed1992

Brown adipose tissue temperature responses following electrical stimulation of ventromedial hypothalamic and lateral preoptic areas or after norepinephrine infusion to Long Evans or Sprague-Dawley rats.

Thermoregulatory (brown adipose tissue temperature) experiments were conducted in age-matched anesthetized, male Sprague-Dawley and Long Evans rats kept at 37 degrees C given unilateral electrical stimulation of the ventromedial hypothalamic nucleus or the lateral preoptic area or after intravenous infusion of norepinephrine HCl (50 micrograms/kg total dose). Unilateral electrical stimulation (0.5 ms pulses of 250 microA at 50 Hz for 30 s) of the ventromedial nucleus or lateral preoptic area caused significant rises (greater than 0.6 degrees C) of intrascapular brown adipose tissue temperature in the Long Evans group only. Norepinephrine infusion (0.1 ml/min for 10 min), or intravenous bolus injection of propranolol HCl (2.5 mg/kg) caused significant yet similar increases (greater than 1.0 degrees C) and decreases (greater than -0.3 degrees C), respectively, of intrascapular brown adipose tissue temperature from pre-administration control temperatures in both Long Evans and Sprague-Dawley groups. The results demonstrate that intrascapular brown adipose tissue sensitivity towards exogenous norepinephrine or propranolol administration is similar between Sprague-Dawley and Long Evans rats acclimated to 21 degrees C as determined by increases in temperature in the intrascapular brown adipose tissue pad. However, intrascapular brown adipose tissue thermogenesis of 21 degrees C-acclimated Long Evans rats is also activated after CNS electrical stimulation of the ventromedial nucleus or lateral preoptic area, an activation not seen in Sprague-Dawley rats suggestive that the latter group has some inhibition of neural pathways that activate brown adipose tissue thermogenesis.

Adipose Tissue, Brown↗

PubMed1993

Peptide-induced grooming behavior and caudate nucleus dopamine release.

We simultaneously measured the display of grooming behavior and, by monitoring the extracellular dopamine concentration via transversal microdialysis, the release of dopamine in the caudate nucleus in freely moving rats after i.c.v. administration of 1 micrograms adrenocorticotropic hormone-(1-24) (ACTH-(1-24)). During a period of 1 h after administration of the peptide, the incidence of excessive grooming behavior was increased. Concomitantly, the concentration of dopamine in the caudate nucleus dialysates was significantly increased (maximal effect 151% of basal release) whereas that of its metabolite DOPAC was unchanged. The potent alpha-melanocyte stimulating hormone (alpha-MSH) receptor agonist, [Nle4,D-Phe7]alpha-MSH, induced grooming behavior and stimulated caudate nucleus dopamine release (maximal effect 148% of basal release) whereas ACTH-(7-16)-NH2 did neither induce grooming behavior nor cause an increase in caudate nucleus dopamine release. Single-dose tolerance was observed for ACTH-induced grooming but not for ACTH-induced dopamine release. These data are in support of the proposed involvement of brain dopamine systems in grooming behavior of the rat but at the same time suggest that the effect of ACTH/MSH-like peptides on dopaminergic transmission in the caudate nucleus is proximal to the final neural pathway involved in ACTH-induced grooming behavior.

Animals↗

PubMed1993

NMDA and non-NMDA antagonists infused into the nucleus reticularis pontis caudalis depress the acoustic startle reflex.

The neural pathway that mediates the acoustic startle reflex has been proposed; however, the pharmacology underlying this reflex is less well known. The present study examined the role of excitatory amino acid receptors at the level of the nucleus reticularis pontis caudalis, a brainstem nucleus obligatory for the whole body startle reflex and implicated as the locus where extrinsic systems such as the amygdala may act to modulate acoustic startle. Twenty-nine rats, chronically implanted with bilateral cannulae aimed at the nucleus reticularis pontis caudalis, were tested to assess the effects of gamma-D-glutamylglycine (DGG), DL-2-amino-5-phosphonopentanoic acid (AP5), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on the amplitude of the acoustic startle reflex. Local infusion of each of the 3 compounds significantly reduced startle amplitude by as much as 70-80%. AP5 and CNQX attenuated startle over a dose range which indicated that the reticularis pontis caudalis may be much more sensitive to these compounds than other nuclei along the primary startle pathway. These results suggest that, at the level of the nucleus reticularis pontis caudalis, an excitatory amino acid neurotransmitter may mediate acoustic startle, and that both NMDA and non-NMDA receptor subtypes may be important for the expression of the acoustic startle reflex.

2-Amino-5-phosphonovalerate↗

PubMed1993

The effect of rhizotomy on NADPH diaphorase staining in the lumbar spinal cord of the rat.

In the L6-S1 spinal segments of the rat NADPH diaphorase fiber-like staining extending along the lateral edge of the dorsal horn to the sacral parasympathetic nucleus was eliminated 1-3 weeks following dorsal-ventral L6-S1 rhizotomy. However, other NADPH diaphorase staining in the dorsal horn was not affected by rhizotomy. Rhizotomy also doubled the number (5 versus 10 cells/section) of NADPH diaphorase positive neurons in the region of the sacral parasympathetic nucleus (SPN). These data indicate that NADPH diaphorase is present in primary afferent projections to the SPN and that NADPH diaphorase activity in SPN neurons can be enhanced by neuronal injury. The functional significance of the NADPH diaphorase histochemical stain remains to be determined; however, if NADPH diaphorase is nitric oxide synthase then this would suggest that NO has an important role in the neural pathways to the pelvic viscera.

Amino Acid Oxidoreductases↗

PubMed1994

The structural and functional development of muscle spindles and their connections in fetal sheep.

In this paper we have studied the structural and functional development of hindlimb muscle receptors and the connections of their afferent fibres in fetal sheep (n = 26) from 67-143 days of gestation (term = 146 days). By recording extracellular discharges in dorsal root ganglia (L7, S1) we have shown that muscle spindle afferents first respond to a ramp-and-hold stretch at mid-gestation (approximately 75 days). Silver-stained preparations of muscle spindles revealed that afferent fibres are just beginning to form annulospiral windings at this age. It therefore appears that the annulospiral formation is not a necessary requirement for the generation of the response. By 87-92 days some receptors had developed a discharge at resting muscle length. Discharges were generally more robust and easier to elicit and static and dynamic components could be identified in the response to stretch. Although static sensitivity was generally low it was more evident than dynamic sensitivity. By 107-115 days it was possible to clearly distinguish between muscle and tendon afferents and to tentatively classify muscle responses as originating from primary or secondary afferent spindle endings. With increasing gestational age there was a progressive increase in the length and complexity of the spindle innervation in parallel with the maturation of functional activity. Biocytin injections into the dorsal root ganglia revealed afferent projections to the motoneuron pools by 67 days. Silver-staining of muscles showed that innervation of extrafusal fibres was also present by this age. We therefore conclude that the neural pathways necessary for reflex activity involving muscle spindles are present and functional from early in gestation and could contribute to early fetal movements.

Afferent Pathways↗

PubMed1995

Estrogen-receptive neurons in the anteroventral periventricular nucleus are synaptic targets of the suprachiasmatic nucleus and peri-suprachiasmatic region.

The anteroventral periventricular nucleus (AVPv) in the rat preoptic area is a key site underlying control of the steroid dependent preovulatory gonadotropin surge. Estrogen and progesterone receptor-containing neurons in the preoptic/hypothalamic continuum, particularly those in the AVPv, are believed to transduce steroidal signals and, in turn convey this information to the LHRH system, which lacks steroid receptors. In addition to the influence of the gonadal steroids, the precise timing of the preovulatory gonadotropin surge is believed to be regulated by the hypothalamic suprachiasmatic nucleus (SCN). The SCN and peri-SCN neurons send efferent projections rostrally to the anterior preoptic area suggesting that circadian signals are communicated synaptically to steroid-responsive neurons in the AVPv. To test this hypothesis, ultrastructural double label immunocytochemistry was conducted to determine whether SCN efferents contact estrogen receptor-immunoreactive neurons in the AVPv. Brain sections with SCN injections of phaseolus vulgaris leucoagglutinin (PHA-L) were immunostained for estrogen receptors and PHA-L. Light and electron microscopic data show that the anterior preoptic area received robust PHA-L-immunoreactive efferents from SCN neurons and immediately adjacent subparaventricular zone. In particular, the AVPv contained abundant labeled fibers and terminal boutons. Ultrastructurally, SCN- and subparaventricular zone-derived terminals synaptically contacted the perikaryon of many estrogen receptor-immunoreactive neurons in the AVPv. The perikarya of unlabeled neurons were also contacted, but the majority of the labeled contacts were observed upon neuronal processes. These results demonstrate that estrogen responsive AVPv neurons are regulated by SCN efferents. Furthermore, the present data provide strong support to the idea of collective control of pituitary gonadotropin release by steroid sensitive and circadian signal neural pathways.

Animals↗

PubMed1995

Involvement of cyclic AMP at the level of the nucleus reticularis pontis caudalis in the acoustic startle response.

Rats were implanted with cannulas in the nucleus reticularis pontis caudalis (PnC), an obligatory part of the neural pathway that mediates the acoustic startle reflex. Following at least 1 week of recovery, rats were tested for acoustic startle amplitude before or after infusion of compounds known to alter the second messenger, adenosine cyclic 3', 5'-monophosphate (cAMP). Local infusion into the PnC of the cAMP analog, 8-bromo cAMP (0.125-1.0 micrograms), increased the amplitude of the acoustic startle response in a dose-dependent manner. In addition, local infusion of a phosphodiesterase inhibitor, rolipram (10 micrograms) or the water soluble adenylate cyclase activator, forskolin-DHA (2.5 micrograms), produced a significant enhancement of startle amplitude. These effects probably resulted from intracellular actions because cAMP itself, which does not readily penetrate lipid membranes, had no effect. Moreover, the effects seemed somewhat specific because the precursor of cAMP, ATP or 8-bromo cGMP, also failed to alter startle at doses where 8 bromo-cAMP did. The fact that a phosphodiesterase inhibitor elevated startle suggests that cAMP serves to tonically elevate startle at this level of the pathway. Hence, treatments that either increase (fear, sensitization) or decrease (habituation, pre-pulse inhibition) startle at the level of the PnC may do so via release of neurotransmitters either positively or negatively coupled to cAMP, which in turn may alter either sound evoked transmitter release, excitability of PnC neurons or both.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Retrograde transfer of replication deficient recombinant adenovirus vector in the central nervous system for tracing studies.

We assessed the application of a replication deficient recombinant adenovirus vector as a retrograde tracer in neural pathway studies. The adenovirus vector, Ad. RSV betagal, containing the intracellular marker gene, beta-galactosidase, was injected directly into the laterodorsal striatum of rats. The retrograde transport of the vector from the injection site was clearly visible in the cerebral cortex, thalamic nucleus, and substantia nigra. No evidence for anterograde transport of the vector was found. When the vector was injected into the genu of the corpus callosum, little uptake of the vector by fibers was noted which suggested that uptake by fibers-of-passage should not be a problem in tracing studies. The present study demonstrates that adenoviral vectors can be useful retrograde tracers in the study of afferent connections within the central nervous system.

Adenoviruses, Human↗

PubMed1996

The glycine/NMDA receptor antagonist HA-966 impairs visual recognition memory in rhesus monkeys.

Recent studies have shown that strychnine-insensitive glycine binding sites positively modulate the N-methyl-D-asparate (NMDA) subclass of glutamate receptors, which are important in neural pathways involved in cognitive function. We examined the effect of (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), a highly specific antagonist of this glycine modulatory site on the NMDA receptor, on visual recognition memory in four rhesus monkeys performing a computer-automated version of delayed nonmatching-to-sample (DNMS) with a list length of 20 trial-unique graphic symbols. In addition, the effect of HA-966 was compared with that of (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (dizocilpine; MK-801), a noncompetitive NMDA channel blocker. Administration of HA-966 (0.1-10 mg/kg, i.m.) 30 min before testing impaired DNMS performance dose-dependently, starting at doses of 3.2 mg/kg; the memory deficity following the highest dose (10 mg/kg) was associated with prolonged response latencies. Similar impairments in recognition memory were observed following treatment with MK-801, though at much lower doses (3.2-32 micrograms/kg) than those at which HA-966 was effective. Administration of low doses of HA-966 (1 mg/kg) and MK-801 (10 micrograms/kg), each of which had no significant effect on performance when given alone, also failed to impair performance when given concurrently. Combined administration of both drugs, each at amnesia-producing doses (3.2 mg/kg of HA-966 plus 32 micrograms/kg of MK-801), markedly impaired performance in an additive, not a synergistic, manner. From these results, we propose that the recognition memory impairment observed in our monkeys following HA-966 administration is via an action on the glycine modulatory site of the NMDA receptor complex.

Animals↗

PubMed1984

Cell lineage analysis of neural induction: origins of cells forming the induced nervous system.

Horseradish peroxidase (HRP) was used as an intracellular lineage tracer in two experiments designed to reveal the sites of origin of cells that formed the duplicate embryo which developed in relation to an organizer grafted in the ventral marginal zone (VMZ) of Xenopus laevis embryos. In the first experiment a dorsal blastoporal lip fully labeled with HRP was grafted in the VMZ of an unlabeled embryo at the beginning of gastrulation. This resulted in development of a second embryo in which labeled cells, of graft origin, formed the notochord, and parts of the somites, endoderm, and neural tube. The second experiment was designed to show the sites of origin of the host's cells that formed parts of the induced embryo. HRP was injected into individual blastomeres in a series of Xenopus embryos at the 32-cell stage and each embryo received an unlabeled organizer graft in the VMZ at the beginning of gastrulation. In these embryos the lineages that contributed to the host's primary neural tube did not contribute any cells to the induced neural tube. All the cells in the induced neural tube which originated from the host were descendants of ventral blastomeres that did not contribute to the neural tube normally. This shows that the second neural tube is formed as a result of the action of the organizer on cells in its immediate vicinity which would not normally have entered neural pathways of differentiation.

Animals↗

PubMed1987

Programmed death of peripheral pioneer neurons in the grasshopper embryo.

The Ti1 pioneer neurons arise at the distal tip of the metathoracic leg in the grasshopper embryo, and are the first neurons in the limb bud to extend axons to the central nervous system (C. M. Bate (1976) Nature (London) 260, 54-56; H. Keshishian (1980) Dev. Biol. 80, 388-397). By providing a neural pathway along which growth cones of later arising neurons migrate, these pioneer axons establish the route of one of the major nerve trunks in the leg (Keshishian, 1980; R. K. Ho and C. S. Goodman (1982) Nature (London) 297, 404-406; D. Bentley and H. Keshishian (1982) Science 218, 1082-1088). Here, we demonstrate that at the 55-59% stage of development, the two Ti1 pioneer neurons undergo programmed death. The role which these pioneers serve in establishing a nerve route appears to be their only function, and may be important for the normal development of the peripheral nervous system. The Ti1 pioneers provide an example of a previously hypothesized class (J. W. Truman (1984) Annu. Rev. Neurosci. 7, 171-188) of programmed neuron death: obsolete neurons whose function was developmental rather than behavioral.

Animals↗

PubMed1990

Embryonic development of the innervation of the locust extensor tibiae muscle by identified neurons: formation and elimination of inappropriate axon branches.

Intracellular dye fills have been used to reveal the pattern of embryonic growth of each of the four neurons which innervate the extensor tibiae muscle (ETi) of the hind leg of the locust. The growth cone of the slow extensor tibiae motoneuron (SETi), the first of the four neurons to leave the central nervous system, pioneers nerve 3 (N3). The fast extensor motoneuron (FETi), the next neuron to grow out, follows earlier outgrowing motoneurons into the periphery in nerve 5 (N5) and then rejoins SETi in N3. As it transfers from N5 to N3, it is transiently dye-coupled to the Tr1 pioneer neuron which spans the gap between the two nerves. It then follows SETi onto the ETi muscle in the femur. The common inhibitory neuron and the dorsal unpaired median neuron (DUMETi) follow SETi and FETi in nerves 3B2 and 5B1, respectively. SETi's growth cone requires almost twice as long to reach ETi as those of the three later motoneurons, all of which follow preexisting neural pathways. At least three of the four developing motoneurons form one or more axon branches not found in the adult. These branches may occur (1) at segmental boundaries; (2) where the nerve, which the growth cone is following, itself branches or the growth cone encounters another nerve; or (3) when the axon continues to grow beyond its target muscle. These findings contrast with the apparent absence of inappropriate axon branches in another developing locust neuromuscular system and during the innervation of zebrafish myotomes, but resemble in some ways the transient production of inappropriate axonal branches reported for embryonic leech motoneurons.

Animals↗

PubMed1980

Brain stem auditory evoked potentials: significant latency differences between ipsilateral and contralateral stimulation.

A number of electrical potentials can be recorded from the human scalp following acoustic stimulation. The potentials which occur within 10 msec of the stimulus onset have been termed the brain stem auditory evoked potentials (BAEPs). Latency appears to be the most stable measure and in consequence knowledge of the exact limits of normal latency of each wave is important. In this study the effects of ipsilateral and contralateral stimulation on BAEP latencies have been investigated in 23 normal subjects. The exact limits of normal latency of each wave have been established. It has been shown that significant latency differences exist between ipsilateral and contralateral stimulation. Possible hypotheses are put forward to explain the findings which demonstrate that different neural pathways are followed by ipsilateral and contralateral stimuli and that their respective responses can be investigated separately in man using BAEP recordings.

Brain Stem↗

PubMed1987

Modulation of reflex and voluntary EMG activity in wrist flexors by stimulation of digital nerves in hemiplegic humans.

Changes in EMG activity in the wrist flexor muscles were studied in response to electrical stimulation of digital nerves and to sudden extension perturbations at the wrist produced by a torque motor in human subjects with unilateral cerebral hemisphere lesions. With the subjects maintaining a steady voluntary contraction against a constant load, digital nerve stimulation produced a series of excitatory and inhibitory changes in tonic EMG activity from the wrist flexors in both the normal and paretic arm. The most consistent response was a period of EMG inhibition beginning approximately 38 msec after the stimulus and lasting approximately 35 msec. With relatively weak electrical stimuli, there was less EMG inhibition in the paretic arm than in the normal arm; with stronger stimuli, the inhibitory response was similar in the two arms. The electrical stimuli and mechanical perturbations were then delivered together, with the interval between them adjusted so that the expected period of inhibition following electrical stimulation coincided with either the early (M1) or the long latency (M2) components of the stretch reflex. In the normal arm electrical stimulation produced more inhibition of the M2 component than of the M1 component. In the paretic arm, inhibition during the M2 component was less marked and similar in degree to that which occurred during M1. These results are compatible with the view that M1 and M2 are normally mediated by separate neural pathways. The long latency EMG activity evoked by muscle stretch in the paretic arm of hemiplegic patients may be generated by pathways or mechanisms different from those in the intact arm.

Electric Stimulation↗