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At least 1,009 records · Page 56Linked to original sources
PubMed1990

In-vivo brain dialysis of neurotransmitters.

Centrally acting drugs interfere with the function of central neurotransmitter systems. This often requires intact neuronal connections and is therefore best studied in vivo. Here, Gaetano Di Chiara describes the technique of brain dialysis, which permits direct in-vivo sampling of neurotransmitters and their metabolites in the brain extracellular fluid. This technique is now providing insight correlating the interaction of drugs with neurotransmission in specific brain areas with their effects on behaviour.

Animals↗
PubMedDate not supplied

A functional role for REM sleep in brain maturation.

The biological function of REM sleep is defined in terms of the functions of neural processes that selectively operate during the REM sleep state. The high amounts of REM sleep expressed by the young during a period of central nervous system plasticity suggest that one function of REM sleep is in development. The phenomenon of activity-dependent development has been clearly shown to be one mechanism by which early sensory experience can affect the course of neural development. Activity-dependent development may be a ubiquitous process in brain maturation by which activity in one brain region can influence the developmental course of other regions. We hypothesize an ontogenetic function of REM sleep; namely, the widespread control of neuronal activity exerted by specific REM sleep processes help to direct brain maturation through activity-dependent developmental mechanisms. Preliminary tests of the hypothesis have been conducted in the developing feline visual system, which has long been known to incorporate information derived from visual experience in establishing neuronal connectivity. We find that suppression of REM sleep processes by an instrumental REM deprivation procedure results in a significant enhancement of the effects of altered visual experience by monocular occlusion. Bilateral brainstem lesions that selectively block the occurrence of ponto-geniculo-occipital (PGO) waves are sufficient to produce similar results. These data indicate that the propagation of phasic influences during REM sleep interacts with other processes subserving neural development. This source of influence appears not to derive from the environment but rather stems from an intrinsic source of genetic origin. Examination of the neural activity associated with PGO waves in the lateral geniculate nucleus reveals a distribution of facilitatory influence markedly different from that induced by visual experience. We conclude that REM sleep directs the course of brain maturation in early life through the control of neural activity.

Animals↗
PubMed1996

Use of a two-hybrid system to investigate molecular interactions of GAP-43.

We used the 'interaction trap' (two-hybrid system) to identify polypeptides that interact with the neuronal phosphoprotein, GAP-43, in an intracellular environment. GAP-43 (neuromodulin, B-50, F1), a protein kinase C (PKC) substrate important for the growth and plasticity of neuronal connections, has been implicated in vitro in several signal transduction pathways. In the yeast-based cloning system, the only strong interaction that was detected between GAP-43 and the calcium effector protein, calmodulin (CaM). PKC phosphorylates GAP-43 on serine 41. When we changed this serine to an aspartate residue to mimic constitutive phosphorylation, the interaction with CaM was blocked. Surprisingly, the N-terminal third of GAP-43 alone bound CaM more strongly than did intact GAP-43, suggesting that the protein's C-terminus may play a role in modulating the interaction with CaM. These results, along with other recent findings, suggest a novel role for the interaction between GAP-43 and CaM.

Calmodulin↗
PubMedDate not supplied

Peptide influences on the development and regeneration of motor performance.

ACTH 1-39 (0.2 U IP daily for up to 18 days) has a beneficial effect on the functional reorganization of regenerating motor units of the extensor digitorum longus (EDL) in the adrenalectomized adult rat following crushing of the peroneal nerve. Motor unit activity (maximum twitch tension amplitude/mean increment in twitch tension as voltage is increased by 0.1 V gradations) and nerve-muscle efficiency (tetanic tension from indirect stimulation/tetanic tension from direct stimulation of EDL) were enhanced by ACTH 1-39. Other electrophysiological and contractile parameters were unaffected by the peptide. Spontaneous motor activity in cold stressed 13 day old rats was prolonged by Org 2766, a substituted analogue of ACTH/MSH 4-9, (0.1 microgram/kg daily) but unaffected by the same dosage of ACTH/MSH 4-10. The responsiveness of developing and regenerating motor systems to neuropeptides indicates a plasticity of neuronal connections, which depends on peptide sequence, dosage and the physiological state of the animal (normal, depressed, regenerating or developing, at rest or stressed).

Action Potentials↗
PubMedDate not supplied

Neuropeptide and monoamine components of the parabrachial pontine complex.

The present investigation examined the distributions of immunoreactive neurotensin (NT), cholecystokinin octapeptide (CCK), substance P (SP), methionine enkephalin (ENK), vasoactive intestinal polypeptide (VIP), somatostatin (SS), rat neurophysin II (RNP II), vasopressin (VP), oxytocin (OXY), tyrosine hydroxylase (TH), and serotonin in the parabrachial nuclear complex (PB) of the rat. All of these substances were localized to the PB and they appeared to be chemoarchitecturally organized within the complex. The lateral subdivision (PBL) was organized medial-lateral and ventral-dorsal. Specifically NT, CCK, and SP immunoreactive fibers were found to be the most dense in the ventral aspect of the PBL. The distribution of NT-containing fibers was similar to the pattern of CCK-containing fibers and these were localized primarily to the central zone of the PBL. Immunoreactive SP fibers and cells were found in the external and internal zones ventrally and surrounding the dorsal and dorsolateral nuclei in the PBL. Somatostatin, ENK and VIP were found to be the most dense in the dorsal PBL. Serotonin- and TH-containing cells and fibers were found in both the PBL and PBM. These results, coupled with the observations of neuronal connections of the PB and the known functions of this region, underscore the potential involvement for these neuropeptides and monoamines in limbic-brainstem mechanisms of autonomic control.

Animals↗
PubMed1991

Selective delayed alternation deficits in dominantly inherited olivopontocerebellar atrophy.

In order to characterize more completely the nature of the frontal lobe-type cognitive changes in patients with dominantly inherited olivopontocerebellar atrophy (OPCA) we administered two tasks sensitive to frontal system dysfunction, delayed alternation (DA) and delayed response (DR), to 12 patients from one OPCA family. Affected members from this family have previously been shown to have a marked and widespread cerebral (including frontal) cortical cholinergic reduction as severe as that observed in Alzheimer's disease. Performance on DA, but not on DR, was significantly impaired in the OPCA patients compared to that in the controls. We suggest that the DA deficits in OPCA could be a consequence of a loss of cholinergic innervation to orbitofrontal or possibly temporal cortical areas and/or damage to the integrity of the cerebello-frontal neuronal connections.

Adult↗
PubMed1987

Hypothalamic pathology in Alzheimer's disease.

The hypothalamus was examined in 3 cases of Alzheimer's disease and 3 control brains, using combined acetylcholinesterase (AChE) and thioflavin-S staining. Neurons undergoing neurofibrillary degeneration were restricted to 3 AChE-positive cell populations (lateral tuberal, lateral posterior and tuberomammillary) that have been found in the rat and monkey to project to the cerebral cortex. Our results suggest that the neurofibrillary degeneration in the hypothalamus involves primarily neurons that innervate cortical areas involved by Alzheimer's disease. This finding is consistent with the hypothesis that Alzheimer's disease is transmitted from neuron to neuron via normal neuronal connections.

Acetylcholinesterase↗
PubMed1991

Bihemispheric organization of amygdalo-cortical projections in the rat.

Two fluorescent dyes were injected symmetrically into the prefrontal cortices of the left and right hemisphere. A consistent number of amygdaloid neurons was labeled from the injection in the contralateral cortex. Each nucleus of the basolateral amygdaloid complex showed a specific pattern of contralaterality. The highest degree of bihemisphericity was observed in the ventral basolateral nucleus. A significant number of neurons connected with the cortex of both hemispheres by means of axon collaterals was observed in the anterior basolateral nucleus. These anatomical findings indicate that the basolateral amygdaloid complex could act as subcortical link for interhemispheric communication.

Amidines↗
PubMed1996

Is there a direct retina-raphe-suprachiasmatic nucleus pathway in the rat?

Possible pathways from the retina to the suprachiasmatic nucleus (SCN) relaying in the dorsal raphe nucleus (DRN) were investigated in rats using combined anterograde and retrograde tracing with immunohistochemistry. After injection of wheat germ agglutinin-conjugated horseradish peroxidase-colloidal gold complex into the SCN, many neurons were retrogradely labeled in the middle levels of the DRN. Approximately one half of these neurons contained serotonin. After injection of cholera toxin B subunit into the eyes, a few anterogradely labeled afferent fibers were detected in the rostral DRN, however, not in contact with retrogradely labeled neurons. Our findings provide direct evidence that serotonergic projections to the rat SCN stem from the DRN nuclei. They also suggest that retina-raphe-SCN projections, a presumed third visual input to the mammalian circadian pacemaker, may include further neuronal connections or brain sites.

Animals↗
PubMed1985

Specific patterns of fibre outgrowth from transplants to host mice hippocampi, shown immunohistochemically by the use of allelic forms of Thy-1.

Foetal mouse hippocampal primordia from mice homozygous for the Thy-1.1 allele were transplanted into the hippocampal region of adult histocompatible mice, homozygous for the Thy-1.2 allele. After survival periods of two months to one year the transplants consisted of a discrete tissue mass, well fused with the host, and distinguished from it by an intense Thy-1.1 immunoreactivity of the neuropil. The host hippocampus was entirely negative for Thy-1.1 immunoreactivity except for well defined projections arising from the transplant. These projections had three different patterns of distribution in the host: (1) a mossy-fibre-like distribution (to the stratum lucidum of field CA3); (2) a fimbria-like distribution (to the stratum oriens and stratum radiatum of fields CA1 and CA3), and (3) a commissural/association-like distribution (to the inner stratum moleculare of the dentate gyrus). Analysis of the position of the transplants and their component cell types indicated that, for each of the three distribution patterns, three conditions had to be fulfilled: (1) the transplant had to contain the appropriate type of cell (granule cells for mossy fibre projections, and larger pyramid-like cells for the other two); (2) the transplant neurons giving rise to the projection had to lie in direct contact with the host field to be innervated, and (3) the terminal field had to be specifically denervated. Thus, for three fibre systems the patterns of transplant-to-host projections observe rules of organization comparable to those of the normal hippocampal circuitry. This implies that in the adult host brain there remain (or there can be elicited) the molecular cues capable of establishing patterns of neuronal connectivity comparable to those formed during normal development.

Animals↗
PubMed1989

Capsaicin-induced stimulation of polymodal nociceptors is antagonized by ruthenium red independently of extracellular calcium.

The dual effect of capsaicin on primary afferent neurons, excitation and stimulation of transmitter release, its dependence on extracellular calcium and its modulation by Ruthenium Red have been investigated in the rabbit ear. Injection of capsaicin into the central artery of the isolated perfused ear with intact neuronal connection induced a reflex fall in systemic arterial blood pressure of the anaesthetized rabbit. Addition of Ruthenium Red (0.6-20 microM) to the perfusate of the ear reversibly attenuated this response in a dose-dependent manner. Perfusion of the ear with a Ca2+-free, 3 mM EGTA-containing physiological salt solution enhanced the capsaicin-evoked depressor reflex but did not prevent the inhibitory action of Ruthenium Red. Perfusion of the isolated rabbit ear with capsaicin (10 microM)-containing physiological salt solution induced the release of substance P-like immunoreactivity which was inhibited by Ruthenium Red (0.6-20 microM) and by omission of extracellular Ca2+. The results demonstrate that capsaicin-evoked transmitter release is dependent on extracellular calcium while capsaicin-evoked excitation is not reduced in a Ca2+-free perfusate. Both effects of capsaicin are potently inhibited by Ruthenium Red. The fact that capsaicin-induced excitation of primary afferents is antagonized by Ruthenium Red also in the absence of extracellular Ca2+ suggests this inhibitory action of Ruthenium Red is not only mediated by inhibition of transmembrane Ca2+ fluxes.

Animals↗
PubMed1991

Sex differences in the development of learning abilities in primates.

The role of steroid gonadal hormones in promoting sex differences in reproductive behaviors has been thoroughly studied in numerous mammalian species. More recent experiments have indicated that the presence or absence of steroid hormones during the critical period of brain differentiation likewise might promote the development of sex differences in cognitive abilities. Studies in infant rhesus monkeys have demonstrated that there exist sex differences in learning abilities that can be altered by perinatal hormonal manipulations, suggesting that testosterone might be a crucial factor responsible for the development of sex differences in cognitive styles. In addition, neonatal lesion studies have shown that the cortical areas mediating specific learning abilities mature at different rates in male and female infant monkeys. These findings support the view that the perinatal hormonal environment can affect the rate of brain maturation by influencing neuronal connectivity at the cortical level. The combined data from sex differences in learning abilities in human infants and their reversibility in endocrinological syndromes suggest that testosterone may affect the maturation of the human brain in a manner similar to that demonstrated in nonhuman primates.

Animals↗
PubMed1991

The physiological role of the pineal gland as the masterswitch of life, turning on at birth breathing and geared to it the function of the autonomic nervous system. The cause of SIDS examined in this context.

The proposition is that the masterswitch of life and death is invested in the physiological role of the pineal gland which by its neurohormonal influence and its neuronal connections in the brain gears hypothalamic noradrenaline levels to which the function of the autonomic nervous system (ANS) and breathing are integrated. Sudden death in an apparently healthy infant can be compared to a well known event, to what happens to a plant if you close the masterswitch which distributes energy. The plant stops to function. It is not yet realized that the human plant also functions only as long as the masterswitch of its biological organization in the brain in charge of energy substrate availability--BOESA--to which breathing, the need of O2, is also geared, is functioning.

Aging↗
PubMed1992

Alzheimer's disease and metal-containing glia.

Considerable evidence suggests that in Alzheimer's disease, olfactory bulb damage may be a primary factor, causing degeneration and neurofibrillary tangles primarily in neurons connected with this brain area. Also, deposits of amyloid may involve an improper regulation of the cleavage of a precursor protein by glia. Finally, toxic effects of aluminium may be an etiological factor. This review proposes that all these seemingly unrelated aspects of Alzheimer's disease could be related to a disturbed function of metal-containing glia. Such a disturbance, initiated by or aggravating toxic effects of aluminum, may underlie initial damage in the olfactory bulb and/or other brain areas with a weakened blood-brain barrier and may be responsible for amyloid deposition.

Aluminum↗
PubMed1986

Ontogeny of adrenomedullary responses to hypoxia and hypoglycemia: role of splanchnic innervation.

Adrenals of neonatal rats were denervated at 3 days of age (just before functional neuronal connections are ordinarily made). At 14 days of age, rats with denervated adrenals did not secrete catecholamines in response to a neurogenic reflex stimulus (insulin-induced hypoglycemia), confirming that innervation had failed to develop; sham-operated littermates were fully responsive to insulin. In contrast, hypoxia was still able to cause depletion of adrenal catecholamines in the denervated group, indicating the persistence of a non-neurogenic secretory mechanism well past the age at which it should have disappeared (8 days). Prolonged deprivation of neural input in adult rats also led to the re-emergence of non-neurogenic capabilities. Twenty-one days after surgery in adulthood, adrenal responses to insulin were still not present but those to hypoxia were. Thus, the development of neural stimulation itself is responsible for the ontogenetic loss of the immature type of adrenal catecholamine release mechanism and does so by suppressing the non-neurogenic component; consequently the mechanism can reappear when nerve traffic is interrupted for extended periods.

Adrenal Glands↗
PubMed1993

Area postrema: gastric vagal input from proximal stomach and interactions with nucleus tractus solitarius in cat.

The responses of neurons in the area postrema (AP) during electrical stimulation of the gastric vagal branches that serve the proximal stomach were evaluated in halothane-anesthetized cats. The evoked orthodromic responses were localized bilaterally in the AP and had a mean latency of 272 ms (SD +/- 53.1). Convergence of gastric vagal input on single AP units from afferents in the ventral and dorsal vagal trunks serving the proximal stomach was observed on 13% of gastric vagally evoked neurons. Reciprocal connections between neuronal populations in the nucleus tractus solitarius and the AP were identified electrophysiologically by direct microstimulation of the former structure. Spontaneously AP discharging units showed an increase in frequency after NTS microstimulation. Our study provided evidence that the AP neurons received vagal input from the proximal stomach and suggested a potential role of the AP in the regulation of food intake.

Afferent Pathways↗
PubMed1988

The effects of intrauterine growth retardation on the development of the Purkinje cell dendritic tree in the cerebellar cortex of fetal sheep: a note on the ontogeny of the Purkinje cell.

The development of the fetal sheep cerebellum at 80, 100, 120 and 140 days gestation (term = 146 days) and 3 months postnatally was studied using Nissl stained sections and rapid Golgi preparations. The most rapid expansion of the Purkinje cell dendritic tree occurred between 100 and 120 days of gestation (5-6 fold increase in area). By 140 days it had acquired its adult form after which time growth continued mainly in the vertical direction. The effects of intrauterine growth retardation on the growth of granule and Purkinje cell dendrites in the cerebellar cortex of fetal sheep (140 days) were investigated in Golgi preparations. Compared with control cerebella the length (but not the number) of granule cell dendrites was reduced by 14% (P less than 0.01); the area of the Purkinje cell dendritic field was reduced by 20% (P less than 0.01); the branching density was reduced by 8% (P less than 0.01); the total branch length was reduced by 27% (P less than 0.002); the density of dendritic spines per row was not affected. These factors resulted in a decrease of 26% (P less than 0.002) in the total number of dendritic spines per row per Purkinje cell. These findings show that the growth of granule cell dendrites and the Purkinje cell dendritic tree have been significantly affected by chronic intrauterine deprivation. Such structural abnormalities could affect the pattern of neuronal connectivity and could be associated with functional deficits.

Animals↗
PubMed1988

Evolution of neurotransmitter-related markers in the vertebrate telencephalon. Comparative microchemical study in discrete brain regions of a frog and a turtle.

1. Neurochemical markers related to cholinergic, GABAergic and glutamatergic/aspartatergic neurotransmission have been measured in telencephalic areas obtained by microdissection from frog (Rana esculenta) and turtle (Pseudemys scripta elegans) brain. 2. In both species, pallial areas showed remarkably higher levels of synaptosomal D-3H-aspartate high affinity uptake than basal regions. Conversely, striatal and septal areas possessed higher levels of the GABAergic marker glutamate decarboxylase (GAD) than the pallium. 3. A differential distribution of GAD was noticed in striatal regions, highest levels of the enzyme being present in the ventral striatum, followed by the nucleus accumbens and the dorsal striatum. 4. Cholinergic markers choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were rather uniformly distributed in the frog telencephalon, while, in the turtle, cholinergic markers were several-fold higher in the basal telencephalon, particularly in the striatum, than in the pallium. 5. The turtle dorsal ventricular ridge possessed ChAT levels more similar to the striatal than to the cortical ones. On the contrary, D-3H-aspartate uptake in the dorsal ventricular ridge was close to the highest levels found in cortical areas. 6. The quantitative neurochemical approach adopted for the present study appears to be a useful tool to investigate the problem of homologies and to gain new information on the evolution of neuron populations and neuronal connections in the vertebrate telencephalon.

Acetylcholinesterase↗