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A Contestabile

Publications and source records attributed to A Contestabile.

At least 91 records · Page 5Linked to original sources
PubMed1984

Evidence for a neurotransmitter role of aspartate and/or glutamate in the projection from the torus longitudinalis to the optic tectum of the goldfish.

Different experimental approaches have been used to demonstrate that aspartate and/or glutamate is a transmitter(s) in the projection from the torus longitudinalis to the marginal layer of the optic tectum in the goldfish. Slices of the optic tectum incubated in vitro in the presence of D-[3H]aspartate and processed for light microscopic autoradiography, demonstrated a preferential accumulation of the labeled compound in the marginal layer. Under the same experimental conditions several neurons in the central part of the torus longitudinalis selectively accumulated D-[3H]aspartate. Synaptosome-enriched preparations from the optic tectum showed high-affinity uptake for D-[3H]aspartate and the rate of the uptake was significantly decreased after disconnection from the ipsilateral torus longitudinalis. The same subcellular preparations showed Ca2+-dependent release of previously accumulated D-[3H]aspartate under high potassium stimulation. This release was significantly reduced in preparations from optic tecta 5 days after cutting their connection with the ipsilateral torus longitudinalis. Finally, D-[3H]aspartate injected in the optic tectum retrogradely labeled the fiber systems connecting the marginal layer with the ipsilateral torus longitudinalis as well as neuronal cell bodies in the torus longitudinalis itself. From autoradiographic experiments it was, in addition, noticed that several tectal neurons selectively accumulated D-[3H]aspartate in the cell bodies as well as in main dendritic trunks. This observation suggests tht aspartate and/or glutamate may be a transmitter(s) in some intrinsic circuits and extrinsic projections of the optic tectum.

Animals↗
PubMed1984

Ultrastructural study of colchicine neurotoxicity in septohabenulointerpeduncular system.

Colchicine is selectively neurotoxic towards some neuronal populations and causes the death of sensitive neurons. Electron microscopic examination of the neural damage caused by stereotaxic injections of colchicine has been used to demonstrate neuroanatomical connections in the septohabenulointerpeduncular system of the rat brain. Colchicine injections in the medial habenula were selectively neurotoxic towards some neurons of the medial habenula and resulted in degeneration of S and crest terminals, the most common type of interpeduncular synapses. Control injections in the stria medullaris, rostral to the habenular complex, caused only sparse degeneration in the interpeduncular nucleus and did not involve S and crest terminals. Colchicine injections that caused neuronal degeneration in the supracommissural septum resulted in substantial terminal degeneration in the interpeduncular nucleus. A large number of degenerated terminals was also present, in these cases, in the medial habenula. Colchicine administration in the various areas caused, to a different extent, lesion or minor ultrastructural damage to axons crossing the injected area. The potential usefulness of colchicine neurotoxicity for neuroanatomical purposes is discussed and the limitation derived from damage of fibers of passage is considered. Colchicine can be confidently used in experimental studies only when erroneous interpretation caused by damage of fibers of passage can be excluded. In the present investigation, this prerequisite could be achieved either by controls made possible by the peculiar arrangement of neuronal circuits or by comparison with known anatomical data.

Animals↗
PubMed1984

Colchicine neurotoxicity demonstrates the cholinergic projection from the supracommissural septum to the habenula and the nucleus interpeduncularis in the rat.

Colchicine injections in the supracommissural septum of the rat caused degeneration of several neurons in the nucleus triangularis septi and the nucleus septofimbrialis. The lesions resulted in significant decreases of choline acetyltransferase in the habenula (-34%) and in the nucleus interpeduncularis (-36%), thus demonstrating the existence of a major cholinergic projection to these nuclei from the supracommissural septum. A large fall in choline acetyltransferase was also noticed in the dorsal hippocampus as a consequence of colchicine damage to the fimbria-fornix fibers crossing the injected area.

Animals↗
PubMed1983

Autoradiographic labeling of the cholinergic habenulo-interpeduncular projection.

The transmitter-specific autoradiographic method has been used to retrogradely trace the habenulo-interpeduncular cholinergic projection. [3H]Choline injection in the interpeduncular nucleus resulted in remarkable labeling of the fasciculus retroflexus and in very strong accumulation of silver grains in the medial habenula. Brainstem nuclei sending non-cholinergic projections to the interpeduncular nucleus were not labeled. The present findings strongly support the notion of a cholinergic medial habenula-interpeduncular nucleus projection in agreement with recent immunohistochemical evidence, but in contrast to previous immunocytochemical and pharmacohistochemical results.

Animals↗
PubMed1983

Cholinergic and GABAergic forebrain projections to the habenula and nucleus interpeduncularis: surgical and kainic acid lesions.

The forebrain cholinergic and GABAergic projections to the habenula and nucleus interpeduncularis have been investigated by means of surgical and kainic acid lesions. Bilateral transection of the stria medullaris caused a 50% decrease of choline acetyltransferase in both the habenula and nucleus interpeduncularis, and a 65% decrease of glutamate decarboxylase in the habenula. Electrolytic lesions of the posterior septum (nucleus triangularis septi and nucleus septo-fimbrialis) accounted for at least 30-40% decrease of the cholinergic parameter in the habenula and nucleus interpeduncularis. Moreover, the choline acetyltransferase decrease in the habenula appeared restricted to the medial part of the nucleus. Kainic acid injections causing very large neuronal destruction in the nucleus of the diagonal band of Broca, and more than 70% decrease of choline acetyltransferase in the dorsal hippocampus, did not affect the cholinergic parameter in either the medial or lateral habenula or nucleus interpeduncularis. Kainic acid injections in the nucleus entopeduncularis resulted in a 40% decrease of glutamate decarboxylase in the habenula. Kainic acid injections in the nucleus of the diagonal band were accompanied by a 40% decrease of glutamate decarboxylase in the medial subdivision only. The present study points at the nuclei of the posterior septum as the source of a major cholinergic projection to the habenula and nucleus interpeduncularis, and reveals a previously unsuspected GABAergic input from the nucleus of the diagonal band to the medial habenula.

Acetylcholine↗
PubMed1983

Pharmacological manipulation of GABA system does not protect the goldfish optic tectum from the neuroexcitatory and neurotoxic action of kainic acid.

Inhibition of GABA transaminase which led to a several-fold increase of GABA levels in the goldfish optic tectum or diazepam pre-treatment, were unable to protect tectal neurons from kainic acid neurotoxicity, as judged by light and electron microscopic observations and by the drop of marker enzymes for neurotransmitters. In an in vitro preparation of tectal slices GABA, added to the incubation medium, had no effect on a metabolic parameter (CO2 production from exogenous glucose) related to the excitatory action of kainic acid. It is concluded that, in the goldfish optic tectum, pharmacological manipulation cannot enhance the activity of GABAergic circuits to the extent necessary to block the neuroexcitatory and neurotoxic action of kainic acid.

4-Aminobutyrate Transaminase↗
PubMed1983

Study of differential effects of kainic acid on metabolic rates, utilizing exogenous or endogenous substrates, in rat brain slices.

CO2 production from exogenous glucose of cortical, whole hippocampal, and CA3 region hippocampal slices, as well as O2 consumption of whole hippocampal slices, were measured in the presence of different concentrations of kainic acid. A moderate, significant increase of CO2 production was seen only in the CA3 region hippocampal preparation at kainic acid concentrations of 10(-4)-10(-2) M. The O2 consumption, at the expense of endogenous energy stores of whole hippocampal slices, was substantially increased by 10(-3) M kainic acid when the slices were incubated without exogenous glucose. The effect was partly paralleled by the use of high (50 mM) K+ concentration. Some of the possible factors involved in the differential metabolic responses of brain slices to the action of kainic acid are discussed briefly.

Animals↗
PubMed1983

Ultrastructural features and acetylcholinesterase histochemistry of the rat habenular complex.

The ultrastructural features and the acetylcholinesterase (AChE) localization of the rat habenula have been studied. On the basis of different morphology and AChE content, it is suggested that at least two types of neurons are present in the medial habenula (MHb) and three types of neurons in the lateral habenula (LHb). In particular, actively AChE-synthesizing neurons have been noticed in both LHb and MHb. Some unusual ultrastructural arrangements of the endoplasmic reticulum have been described in habenular neurons. Finally, the most common types of synaptic contacts present in the habenular complex have been surveyed.

Acetylcholinesterase↗
PubMed1982

Acetylcholinesterase Histochemistry of the habenulo-interpeduncular pathway in the rat and the effects of electrolytic and kainic acid lesions.

The histochemical distribution of acetylcholinesterase (AChE) was studied in the habenulo-interpeduncular pathway of normal rats and after electrolytic and kainic acid lesions of the habenular nuclei. From these combined observations it appears that the AChE-rich projection to the interpeduncular nucleus derives from both the medial and the lateral habenular nuclei. The lateral nucleus of the habenula is the main source of AChE-rich fibres in the fasciculus retroflexus, and a number of stained fibres also derive from the stria medullaris. While total habenular lesion completely deprived the fasciculus retroflexus of AChE-stained fibres, a direct effect on the enzyme distribution in the interpeduncular nucleus was only apparent as its rostral pole. In the remainder of the nucleus the AChE distribution did not undergo obvious changes in comparison with the normal pattern, except for a moderate decrease in overall reaction intensity in cases with subtotal habenular lesion bilaterally. The above results are consistent with the observation derived from experiments involving kainic acid injection into the habenula. The neurotoxic effect of kainic acid was highly selective for specific types of neurons in the lateral habenula, while the neurons of the medial habenula were completely unaffected. The existence of an AChE-rich projection from the lateral habenula to the interpeduncular nucleus was supported by a corresponding decrease in enzyme activity in the lateral habenula and fasciculus retroflexus after kainic acid treatment.

Acetylcholinesterase↗
PubMed1982

Neurotoxic effect of kainic acid on ultrastructure and GABAergic parameters in the goldfish cerebellum.

Kainic acid administration into the cerebellar dorsal lobe of the goldfish causes selective degeneration of some neuronal types. Stellate and Golgi neurons are very sensitive to the neurotoxin and undergo rapid degeneration. On the basis of their differential responses to kainic acid, Purkinje cells can be divided in two distinct sub-populations (i.e. sensitive and insensitive neurons). The degenerative changes of the Purkinje neurons are in addition remarkably slow in comparison with the same cells in mammals or with stellate and Golgi neurons in the goldfish. Granule cells, as well as the cerebellar afferent fiber system, are not significantly affected. Six days after kainic acid administration, the level of glutamate decarboxylase in the cerebellar dorsal lobe drops to about 40% of the control value. This result suggests that the neurons sensitive to kainic acid neurotoxicity are, at least in part, GABAergic. Light- and electron-microscopic autoradiography of cerebellar elements selectively accumulating [3H]GABA, supports this idea. Moderate decreases of acetylcholinesterase and protein content were also noticed in the kainic acid-treated cerebellar dorsal lobe.

Acetylcholinesterase↗
PubMed1982

Effect of kainic acid, glutamate, and aspartate on CO2 production by goldfish tectal slices.

For a study of the excitatory effect of kainate, glutamate, and aspartate in the goldfish optic tectum, these substances were tested on the production of CO2 from radioactive glucose in tectal slices incubated in Krebs-Ringer medium for fish. Kainate increased the rate of CO2 production for up to 30 min in a dose-related manner, the effect being maximum at 0.1 mM concentration and decreasing at higher doses. The effect was blocked by ouabain (1 mM) as well as by the substitution of choline for Na+ in the incubation medium. Glutamate and aspartate exerted a less pronounced excitatory effect on CO2 production at higher concentration than kainate. This effect was also abolished by ouabain. Glutamate, added to the medium at a concentration at least 100-fold higher than kainate, partially reversed the increase in CO2 production induced by kainic acid. No similar effect was noticed for aspartate. The supposed glutamate antagonists glutamic acid diethylester (1 mM) and proline (5 mM) did not affect the excitatory action of kainic acid or exert an antagonistic effect towards glutamate. At higher concentration (10 mM) glutamic acid diethylester increased CO2 production, an effect that was, however, ouabain insensitive. Methyltetrahydrofolic acid (1 mM), a substance reported to compete for the kainate receptor, did not inhibit the effect of kainic acid or increase CO2 production.

Animals↗
PubMed1982

Cytochemical study of cholinesterases in the normal and retino-derived optic tectum of reptiles.

An electron microscopic histochemical study has been carried out on the localization of acetylcholinesterase (AChE) in the optic tectum of a lizard and a turtle. Several types of AChE-synthetizing elements have been described. In both species these neurons constitute only a fraction of the total neuronal popultio- of the optic tectum. The area of maximum accumulation of AChE activity is in both cases at level of the neuron pil of the stratum fibrosum et griseum superficiale, where most retinal afferents are known to terminate. There is however a peculiar difference in the ultrastructural localization of the enzyme activity in the stratum et fibrosum et griseum superficiale of the two species. While in the turtle most activity is localized inside dendritic structures, a definite prevalence of extracellular localization, including synaptic spaces, has been noticed of the lizard. The main effect of eye deprivation on AChE localization in the optic tectum has been noticed for the lizard, in which a remarkable decrease of extracellular AChE occurs 2 months after contralateral enucleation. In the lizard a peculiar localization of pseudocholinesterase AChE occurs 2 months after contralateral enucleation. In the lizard a peculiar localization of pseudocholinesterase (BuChE) has been in addition demonstrated in the spaces between axon bundles in the stratum opticum and stratum album centrale. The relevance of these findings is briefly discussed also in relation to the existence of cholinergic mechanisms of neurotransmission in the optic tectum.

Acetylcholinesterase↗
PubMed1982

Electron microscopic demonstration of neurons and synaptic terminals selectively accumulating (3H)GABA in goldfish optic tectum.

After injection of (3H)GABA in the goldfish tectum, several neural structures selectively accumulating the labeled neurotransmitter were revealed by electron microscopic autoradiography. A number of labeled neurons was observed in the periventricular layer, while some scattered neurons were present in more superficial layers. Different types of axon terminals were also labeled in the stratum marginale, stratum fibrosum and griseum superficiale and stratum griseum centrale. Labeled dendrites, in particular those belonging to the periventricular neurons, were also noted.

Animals↗
PubMed1981

Kainic acid neurotoxicity does not depend on intact retinal input in the goldfish optic tectum.

Kainic acid neurotoxicity has been studied in the optic tectum of the goldfish 4 weeks after eye enucleation. The effect of drug treatment has been tested with respect to both neurochemical and morphological parameters. The neurotransmitter-related enzymes, choline acetyltransferase, acetylcholinesterase and glutamate decarboxylase, show about 50% decrease in the deafferented tectum 6 days after kainic acid administration. Relevant morphological alterations of the tectal structure can also be noticed at the same stage. The neurotoxic effects of kainic acid in the deafferented optic tectum are therefore quite similar to the effects of previously noticed for the intact optic tectum of normal fish. Control experiments on the effect of optic nerve degeneration by itself on the levels of the neurotransmitter-related enzymes in the optic tectum, have shown no significant decrease in glutamate decarboxylase, a slight decrease in acetylcholinesterase and a more marked drop in choline acetyltransferase. The findings are discussed with reference to some of the hypotheses advanced in order to explain kainic acid neurotoxicity. It is proposed that the neurotoxic effect of kainic acid after removal of specific excitatory afferents, may vary in different nervous centers depending on differences of the remaining extrinsic connections and of the intrinsic neural circuits.

Acetylcholinesterase↗
PubMed1981

Afferent connections of the interpeduncular nucleus and the topographic organization of the habenulo-interpeduncular pathway: an HRP study in the rat.

The HRP tracing method was employed to investigate the organization and afferent connections of the interpeduncular nucleus (IPN) in the rat. To study the topographical features of the different projections, a method was devised for obtaining HRP placements of limited size in different areas of the IPN. The main afferent connection of the IPN is a topographically organized projection from the medial habenula (Hb). This projection follows a reversed caudorostral pattern, terminating throughout all but the caudalmost part of the IPN. The dorsal part of the IPN receives a sparse innervation arising mainly from a narrow lateral and ventrolateral area of the medial Hb. The ventral two thirds of the IPN receives a much heavier projection, as follows: A large ventrolateral area of the medial Hb projects to the lateral part of the IPN in a completely bilateral way. An additional projection, which is predominantly ipsilateral, arises from the rostral half of the dorsolateral part of the medial Hb and terminates in the caudal IPN. The medial part of the medial Hb projects preferentially to central areas of the IPN. The projection from the lateral Hb is quantitatively much smaller but appears to be distributed to the entire length of the IPN, following a nonreversed caudorostral arrangement, with the ipsilateral projection predominating. The projections from the medial and lateral Hb to the IPN were confirmed by tracing anterogradely transported HRP as well. No reciprocal connection from the IPN to the Hb could be demonstrated. A sparse projection to the IPN with a strong ipsilateral predominance arises from the horizontal limbs of the nucleus of the diagonal band of Broca. This was the only projection observed from the septal region. Sparse projections from the premammillary and supramammillary nuclei were also demonstrated. Confirmatory data and some details of organization were also obtained for projections to the IPN from other areas, including the medial and dorsal raphe nuclei, the dorsal tegmental nucleus of Gudden, and the adjacent dorsolateral tegmental nucleus. Very small projections from the ventral tegmental nucleus and the locus coeruleus were also found.

Afferent Pathways↗