Biomedical subjects

C Köhler

Publications and source records attributed to C Köhler.

At least 145 records · Page 8Linked to original sources

PubMed1984

Light and electron microscopic localization of glutamic acid decarboxylase and substance P in the dorsal column nuclei of the cat.

Using immunocytochemical methods, glutamic acid decarboxylase (GAD)-immunoreactive boutons were demonstrated throughout the dorsal column nuclei of the cat brain. They were small and were generally presynaptic to larger unlabelled axon terminals, the latter probably originating from primary afferent fibres. The middle-ventral 'reticular' region of the cuneate nucleus also contained substance P-positive terminals, which were large and synapsed on dendritic profiles. The findings strongly indicate that gamma-aminobutyric acid (GABA) is the neurotransmitter that is responsible for the presynaptic inhibition in the dorsal column nuclei. The substance P-positive terminals probably originate from extrinsic fibers.

Animals↗

PubMed1984

The projection of the supramammillary nucleus to the hippocampal formation: an immunohistochemical and anterograde transport study with the lectin PHA-L in the rat.

The organization and possible neurotransmitter specificity of a projection from the lateral supramammillary nucleus to the hippocampal formation has been examined with immunohistochemical and axonal transport methods in the adult male rat. Experiments with the retrograde tracer true blue indicate that neurons throughout the rostrocaudal extent of the nucleus are labeled after injections in either dorsal parts of the dentate gyrus and Ammon's horn, or the entorhinal area, although cells labeled by the entorhinal injections tended to occupy more ventral parts of the nucleus. Combined immunohistochemical-retrograde transport studies showed that a small number (less than 5%) of cholecystokinin-immunoreactive neurons in the caudal tip of the supramammillary nucleus project to the hippocampal formation, as do some (5-10%) vasoactive intestinal polypeptide (VIP)-immunoreactive neurons throughout the nucleus. Anterograde transport studies with the lectin phaseolus vulgaris leucoagglutinin (PHA-L) indicate that fibers from the supramammillary nucleus innervate all parts of the hippocampal formation. Many varicose fibers with terminal boutons were observed in the granular and molecular layers of the dentate gyrus, throughout the molecular layer of field CA3 of Ammon's horn, and in the pyramidal layer and stratum oriens of subfield CA3a. Only scattered fibers were found in fields CA1 and CA2. Apparent terminal fields were also observed in superficial parts of the molecular layer, and deep parts of the pyramidal layer, of the subiculum, in the deepest layer of the presubiculum and parasubiculum, and in all layers of the entorhinal area.

Animals↗

PubMed1984

Acetylcholinesterase-containing cells in the lateral hypothalamic area are immunoreactive for alpha-melanocyte stimulating hormone (alpha-MSH) and have cortical projections in the rat.

Small injections of the retrograde fluorescent tracer Fast blue into different cortical areas, including the hippocampal region, labeled cells in the zona incerta and the lateral hypothalamic area. A majority (approximately equal to 90%) of the retrogradely labeled cells cross-reacted with an anti-serum to the opioid peptide alpha-melanocyte stimulating hormone (alpha-MSH). Sequential staining of the same tissue sections showed that a majority of the alpha-MSH stained cells in the lateral hypothalamic area and the zona incerta also contain the enzyme acetylcholinesterase (AChE) but not cholineacetyltransferase. These results suggest that cortical AChE resides partly in non-cholinergic terminals and that some of these arise from alpha-MSH immunoreactive cells in the hypothalamus and subthalamus.

Acetylcholinesterase↗

PubMed1984

Distribution of tyrosine-hydroxylase-immunoreactive neurons in the hypothalamus of rats.

The distribution and morphology of cells containing tyrosine hydroxylase (TH) immunoreactivity in the hypothalamus of rats were studied by using a modified immunoperoxidase technique. The TH cell system is more complexly organized than was previously thought. On the basis of their clustering patterns, hypothalamic TH neurons could be subdivided into two groups: dorsal and ventral. The ventral group consists of a prominent aggregate of cells located in the caudal part of the arcuate nucleus. From here, cells extend around the caudal part of the ventromedial and dorsomedial nuclei and the base of the diencephalon. Tyrosine hydroxylase-positive cells are present throughout the arcuate nucleus, except in its ventromedial part. Anteriorly, immunoreactive cells appear in the suprachiasmatic and supraoptic nuclei, in the retrochiasmatic area, and in the ventral part of the anterior hypothalamic nucleus. The dorsal group has its main concentration of cells in the medial part of the zona incerta, from which two clusters of cells, one medial and one lateral, extend rostralward. The medial group comprises cells in the medial part of the dorsomedial, paraventricular, and anterior hypothalamic nuclei. These cells adjoin the periventricular cells. The lateral group of cells emanating from the zona incerta occupies the lateral part of the dorsomedial and anterior hypothalamic nuclei and the dorsal hypothalamic area. The dorsal and ventral TH cell groups are in continuity medially in the periventricular layer, and laterally through the cells that surround the ventromedial nucleus. Although the cells vary widely in size, shape, and dendritic arborization pattern, there are two main cell types. Small (21 X 11 microns), round to fusiform cells, with two or three dendrites arborizing simply, were frequently seen in the arcuate, suprachiasmatic, periventricular, supramammillary nuclei and at the borders of the ventromedial nucleus. The other cell type is larger (40 X 15 microns) and multipolar, with three to five frequently branching dendrites. The dendritic field is large and the cells are intensely TH-immunoreactive. Although the larger cells occur occasionally in every hypothalamic nucleus, their principal locations are in the dorsal parts of the dorsomedial, posterior hypothalamic nuclei and the dorsal and lateral parts of the zona incerta, and in the areas dorsal and medial to the mammillothalamic tract at caudal hypothalamic levels. In this paper we give a detailed description of TH-immunoreactive fibers and terminals in the hypothalamus and a comparison with previous studies of catecholamine cells in the hypothalamus.

Animals↗

PubMed1984

Ibotenate-induced neuronal degeneration in immature rat brain.

Stereotaxic microinjections of the excitotoxin, ibotenic acid, were made into the striatum, hippocampus or cerebellum of the immature (7-day-old) rat. Two days later, pups were decapitated and the brains processed for light microscopic examination or neurochemical analyses. 10 micrograms ibotenate caused a complete loss of nerve cell bodies throughout the striatum and hippocampus while intracerebellar injections produced no detectable damage. In the striatum, catecholamine histofluorescence was abolished and dopamine uptake severely reduced, indicating also a loss of afferent nerve terminals. Co-injection of 10 micrograms ibotenate with equimolar amounts of the selective amino acid antagonist, (-)-2-amino-7-phosphonoheptanoic acid, resulted in the protection of both striatal cell bodies and dopaminergic nerve terminals. The neurotoxic properties of ibotenate described here are in marked contrast to those of kainic acid, a related excitotoxin. Differences in the ontogenetic pattern of receptors which mediate neurodegenerative events may account for the pharmacological and regional selectivity and the partial lack of axon-sparing properties of ibotenic acid lesions in the immature brain.

2-Amino-5-phosphonovalerate↗

PubMed1984

Remoxipride, a new potential antipsychotic compound with selective antidopaminergic actions in the rat brain.

The novel substituted benzamide, remoxipride, preferentially blocked apomorphine-induced hyperactivity with weak effects on stereotypies. The potency of remoxipride was about 50 times higher than that of sulpiride. Remoxipride caused a weak, atypical form of catalepsy and showed a high separation between the ED50 for blockade of apomorphine-induced hyperactivity and the ED50 for induction of catalepsy (ratio 24). Remoxipride was shown to be a selective dopamine D2 receptor antagonist since it displaced [3H]spiperone (IC50 = 1570 nM) but not [3H]flupentixol (IC50 greater than 100 000 nM) in rat striatum, and did not inhibit striatal DA-sensitive adenylate cyclase in vitro (IC50 greater than 100 000 nM). Remoxipride is a potent antagonist of D2 receptors showing a dose-dependent blockade of [3H]spiperone and [3H]n-propylnorapomorphine in vivo binding with a potency equal to that of chlorpromazine. In contrast to haloperidol, remoxipride caused a preferential blockade of in vivo [3H]spierone binding in the mesolimbic DA rich areas and the substantia nigra with much less effect in the striatum. In addition, remoxipride produced a preferential increase of DA utilization following synthesis inhibition in the olfactory tubercle. Only minor changes in NA and 5-HT metabolism were observed while HVA and DOPAC levels were markedly elevated. Taken together, these results indicate that remoxipride is a potent, selective D2 receptor blocking agent with a preferential action in mesolimbic and extrastriatal dopamine-containing neurons.

Adenylyl Cyclases↗

PubMed1984

Excitotoxic models for neurodegenerative disorders.

In recent years, considerable interest has been shown in the neurotoxin properties of excitatory amino acids and their possible relevance for the study of human neurodegenerative disorders. The term "excitotoxin" has been coined for a family of acidic amino acids which are neuroexcitants and produce a characteristic type of "axon-sparing" neuronal lesion. Intracerebral infusions of kainic and ibotenic acids, the two most commonly used excitotoxins, result in a morphological and biochemical picture in experimental animals which resembles that observed in the brains of Huntington's disease and epilepsy victims. The emergence of such animal models for neurodegenerative disorders has led to the hypothesis that endogenous excitotoxins may exist which are linked to the pathogenesis of human diseases. The most promising candidate discovered so far is quinolinic acid, a hepatic tryptophan metabolite which has recently also been found to occur in brain tissue. The particular excitotoxic properties of quinolinic acid warrant a thorough investigation of its metabolic and synaptic disposition in normal and abnormal brain function. While little is known about the mechanisms by which excitotoxins cause selective neuronal death, most current speculations propose the participation of specific synaptic receptors for acidic amino acids. The recent development of selective antagonists of such receptors has aided in the elucidation of excitotoxic mechanisms. Although a biochemical link between endogenous excitotoxins and human neurodegenerative disorders remains elusive at present, pharmacological blockade of excitotoxicity may constitute a novel therapeutic strategy for the treatment of these disease states.

Amino Acids↗

PubMed1984

A study of the reciprocal connections between the septum and the entorhinal area using anterograde and retrograde axonal transport methods in the rat brain.

The reciprocal connections between the septum and the entorhinal area (EA) was studied in the rat brain using antero- and retrograde axonal transport methods. After injections of large volumes (2 X 100 nl) of horseradish peroxidase (HRP) conjugated to wheat-germ agglutinin (WGA) into the medial septum (MS) and the diagonal band of Broca (dbB), anterogradely transported HRP-WGA was found primarily in layers II and IV of the medial and lateral EA. Injections of HRP-WGA (50-100 nl) or fluorescent dyes (50-100 nl) into different parts of the retrohippocampal region resulted in labeling, by retrograde axonal transport, of cells in the MS and dbB, both ipsi- and contralateral to the injected hemisphere. The labeled cells were either small (long axis of soma: 10-15 micron), round, and oval, or medium (15-25 micron) to large (25-35 micron) of fusiform or multipolar shape. By using the method of retrograde fluorescent double labeling, the septal afferents to the EA were found to give off collaterals to other parts of the hippocampal region. A much smaller number of septal cells appeared to send bilateral projections to the EA of both hemispheres. Studies employing retrograde transport of HRP in combination with acetylcholinesterase (AChE) histochemistry on the same tissue section showed that, while a large number of cells projecting to the EA contain AChE, many projecting cells are devoid of AChE reaction products. These findings suggest that the septo-entorhinal projection consists of a cholinergic as well as a noncholinergic component. The entorhinal efferents to the septum were studied after injections of HRP-WGA into different parts of the retrohippocampal region. Labeled fibers could be traced through the fimbria to their terminal fields in the intermediate parts of the lateral septal nucleus and to the most lateral aspect of the vertical limb of the dbB. The cells giving rise to this projection were situated in layer IV of the medial and layers II through V of the lateral EA. Taken together, the present findings demonstrate a close anatomical relationship between the septum and the entorhinal area, in addition to the better known connections between the septum and the Ammon's horn.

Acetylcholinesterase↗

PubMed1984

Autoradiographic mapping of spirodecanone binding-sites in the hippocampal region of the rat. Evidence for a localization on intrinsic neurons.

The method of in vitro receptor autoradiography was used to map the distribution of spirodecanone binding-sites in the rat hippocampal region. Incubations of horizontal sections through the hippocampus with [3H]spiperone (1 nM) resulted in dense labeling restricted to the pyramid cell layer in CA1, the parasubiculum and layers I and II of the entorhinal area (EA), while the other hippocampal subfields contained moderate to low binding. ADTN, serotonin, ketanserin and mianserin (1-100 microM) all failed to displace the [3H]spiperone in the layers of densest binding, while displacement of the [3H]spiperone binding occurred with high concentrations of spiperone (1 microM) and haloperidol (100 microM). Intra-entorhinal injections of the neurotoxin ibotenic acid prevented [3H]spiperone binding to layers I and II of the EA, while transections of septal and commissural afferents or the degeneration of serotonin and noradrenaline terminals appeared not to reduce the [3H]spiperone binding in any part of the hippocampal region. These findings suggest that spirodecanone binding-sites are located on intrinsic neurons in restricted laminae of the hippocampal region.

Animals↗

PubMed1984

Morphological details of the projection from the presubiculum to the entorhinal area as shown with the novel PHA-L immunohistochemical tracing method in the rat.

Iontophoretic injections of the lectin, phaseolus vulgaris leucoagglutinin (PHA-L) were made into the presubiculum of rats. The anterogradely transported lectin was visualized by using an anti-PHA-L antibody in combination with immunohistochemistry. The PHA-L tracing method revealed morphological details of the projection of the presubiculum to the ipsi- and contralateral medial entorhinal area usually not seen with other anterograde transport techniques. Fine varicose fibers form a dense terminal plexus in the deep parts of layer III. In layer II and deep layer I, the fibers form column-like axonal bundles, terminating in patches in the deep part of layer I. Some fibers reach the outer three layers of the entorhinal area (EA) from collaterals of axons running in the molecular layer, while a majority enter from the deep layers.

Animals↗

PubMed1984

A diffuse alpha MSH-immunoreactive projection to the hippocampus and spinal cord from individual neurons in the lateral hypothalamic area and zona incerta.

The course, distribution, and possible neurotransmitter specificity of a projection from the lateral hypothalamic area (LHA) and zona incerta to the hippocampal formation (dentate gyrus, Ammon's horn, subicular region, and entorhinal area) and spinal cord were examined anatomically in the adult rat. First, small injections of the fluorescent tracer fast blue were made into either the septal part of the dentate gyrus and Ammon's horn or the entorhinal area, and the distribution of retrogradely labeled cells was plotted. In each experiment many cells were labeled in the LHA and zona incerta, and little evidence for a topographically organized projection to different parts of the hippocampal formation was found. Second, a combined retrograde transport-immunofluorescence method was used to show that some 95% of the fast blue-labeled neurons in the LHA and zona incerta were also stained with an antiserum to the opiate peptide alpha-melanocyte-stimulating hormone (alpha MSH), but not an antiserum to adrenocorticotropin (ACTH)1-24. It was also found that small numbers of retrogradely labeled neurons were stained with antisera to somatostatin 14 and 28, dynorphin (1-17), and angiotensin II. Third, the distribution of alpha MSH-immunoreactive fibers was plotted, and they were found to form a diffusely organized plexus throughout all of the subfields of the hippocampal formation. These fibers were virtually eliminated after transections of the fimbria and the region between the entorhinal area and the caudal amygdala. Forth, the course of fibers from the LHA and zona incerta was examined with the anterogradely transported lectin Phaseolus Vulgaris Leucoagglutinin (PHAL). Such fibers reach the hippocampal formation by a dorsal route through the septal region and fimbria, and by a ventral route through the amygdala. And fifth, double retrograde transport and immunohistochemical methods were used to show that at least some alpha MSH-stained neurons in the LHA and zona incerta give rise to collaterals that innervate both the hippocampal formation and the spinal cord. Alpha MSH-stained fibers in the spinal cord also form a widely scattered plexus with no obvious circumscribed terminal fields. It is suggested that the diffusely organized projection from the LHA to the cerebral cortex and spinal cord may play a role in the general arousal associated with a variety of motivated behaviors.

Animals↗

PubMed1984

Golgi-like immunoperoxidase staining of dopamine neurons in the reticular formation of the rat brainstem using antibody to tyrosine-hydroxylase.

The distribution and morphology of presumed dopaminergic neurons within the reticular formation (RF) and the ventrolateral tegmental area (VLT) were studied by using a specific antibody to the enzyme that converts tyrosine to dihydroxyphenylalanine, tyrosine-hydroxylase (TH), in combination with a sensitive immunoperoxidase method (Hsu et al., '81). Incubation of thick (70-120 micron) sections for 3-5 days in high dilutions of antibody resulted in staining of TH-immunoreactive neurons in a Golgi-like fashion. Analysis of serial sections cut in the coronal, horizontal, and parasagittal planes revealed an extensive system of TH-positive neurons in the RF and VLT extending from the Edinger-Westphal nucleus caudally to the level of the decussations of the superior cerebellar peduncle. Within this region, the TH-positive cells belong to two subgroups: (1) a relatively well-defined population of cells aggregated in the reticular formation (corresponding to cell group A8 of Dahlström and Fuxe, '64), and (2) a more loosely defined group of cells that appears to be continuous with the cells of the nucleus raphe linearis. This latter cell group extends laterally from the midline to the nucleus parapeduncularis. An analysis of the individual TH-immunoreactive cells revealed large differences in their morphology. Thus, the somata of TH-positive cells in the RF and the VLT are fusiform, ovoid, or triangular. A majority of the TH neurons are of medium (long axis: 15-35 micron) to large (long axis: 35-40 micron size. While the cells in the A8 area appeared relatively homogeneous, the TH-positive cells of the VLT showed great variations in dendritic branching pattern and orientation. Taken together, the present study has shown that within the RF and the VLT, the TH-immunoreactive neurons are more numerous than hitherto recognized, and that this cell group consists of a morphologically heterogeneous population of dopamine-synthesizing neurons.

Animals↗

PubMed1984

Septal neurons containing glutamic acid decarboxylase immunoreactivity project to the hippocampal region in the rat brain.

Injections of the fluorescent dyes Fast Blue or Granular Blue into either the hippocampus (volume approximately 50 nl) or the entorhinal area (100-150 nl) resulted in labeling by retrograde axonal transport of cells in the diagonal band of Broca (dbB) and the medial septum (MS). A large number (approximately 30%) of these cells contained glutamic acid decarboxylase (GAD)-like immunoreactivity, as determined by combined retrograde fluorescent tracing and GAD-immunohistochemistry. Not all GAD positive cells in the dbB and MS were labeled by fluorochromes in a single experiment. The GAD-stained and fluorochrome-containing cells were present at all rostro-caudal levels of the septum and appeared not to belong to any single morphological class of cells. Double staining experiments showed that the GAD-positive cells did not contain acetylcholinesterase reaction product. These findings provide evidence that a significant portion of the septo-hippocampal projection may utilize gamma-aminobutyric acid as a neurotransmitter.

Animals↗

PubMed1984

An immunohistochemical study of somatostatin and neurotensin positive neurons in the septal nuclei of the rat brain.

Antibodies to the neuropeptides somatostatin (SOM) and neurotensin were used to study the distribution of the two peptides within the septum of the rat brain. In colchicine treated rats, numerous somatostatin-positive cell bodies were found in the dorsal and ventral subdivisions of the lateral septum, along the border of the nucleus accumbens, in the ventral tip of the horizontal limb of the diagonal band of Broca as well as in the anterior hippocampal rudiment, infralimbic area and several other structures of the basal forebrain (e.g., nucleus accumbens, olfactory tubercle and substantia innominata). Cell bodies containing immunoreactivity for neurotensin were situated in the intermediate and ventral subdivisions of the lateral septum, the medial septal nucleus, the diagonal band of Broca, the rostro-medial continuation of the substantia innominata and the olfactory tubercle. In untreated rats, somatostatin positive processes formed terminal plexuses in the medial septal nucleus and along an area close to the ventricular wall of the lateral septal nucleus. Other septal nuclei, such as the diagonal band of Broca contained a sparse innervation by somatostatin positive fibers. In contrast, the nucleus accumbens, olfactory tubercle, and the substantia innominata contained a rich innervation by somatostatin positive axons and terminals. Within these structures the density of SOM positive processes show great variations with patches of densely packed terminals separated by areas of sparser or no innervation. The neurotensin positive terminals were situated predominantly within the intermediate part of the lateral septum and the medial septal nucleus. Both of these regions contained numerous pericellular baskets of neurotensin positive terminals around septal neurons. In addition to the septal innervation, several of the basal forebrain structures were rich in neurotensin positive processes with the densest innervation found in the nucleus accumbens and substantia innominata. Like the SOM-immunoreactivity distinct islands of dense neurotensin innervation separated by less or no innervation occur throughout the basal forebrain. Taken together, these findings suggest that somatostatin and neurotensin occur in separate neuronal populations and that each may influence important physiological functions within the individual septal nuclei.

Animals↗

PubMed1984

The distribution of serotonin binding sites in the hippocampal region of the rat brain. An autoradiographic study.

The distribution of serotonin binding sites was studied in the rat hippocampal region by using contact-film autoradiography after in vitro incubations of brain sections with 5-[3H]hydroxytryptamine, [3H]spiperone, and [3H]ketanserin, respectively. Biochemical studies of the 5-[3H]hydroxytryptamine binding to sections cut through the hippocampal region showed that at saturating concentrations of 5-[3H]hydroxytryptamine (2-2.5 nM) the specific binding was at least 50% of the total. The 5-[3H]hydroxytryptamine binding sites were found to be heterogeneously distributed within the hippocampal region with the highest densities present in the following parts: layers I and II and layers IV through VI of the entorhinal area, the radial layer of the subiculum and subfield CA1 of the Ammon's horn and the molecular layer of the area dentata. Moderate to low densities of binding was observed in layer III of the entorhinal area, the pre- and parasubiculum, the stratum pyramidale of the Ammon's horn, and the granular cell layer of the area dentata. Removal of the 5-hydroxytryptamine nerve terminals by systemic injections of the 5-hydroxytryptamine neurotoxin parachloroamphetamine resulted in no detectable reductions of 5-[3H]hydroxytryptamine binding in any brain region. Lesions of hippocampal cell bodies by intrahippocampal injections of ibotenic acid prevented the binding of 5-[3H]hydroxytryptamine within the area of the cell loss. Comparisons between the distribution of 5-hydroxytryptamine immunoreactive nerve terminals and the 5-[3H]hydroxytryptamine binding sites showed that in some areas of sparse 5-hydroxytryptamine innervation the 5-[3H]hydroxytryptamine binding was close to background (e.g. the pyramidal cell layer, the stratum lucidum) whereas in areas with little 5-[3H]hydroxytryptamine binding (e.g. layer III of the lateral entorhinal area, the presubiculum) a very dense 5-hydroxytryptamine innervation was found. The hippocampal 5-[3H]hydroxytryptamine binding was displaced neither by ketanserin (1 microM) nor by spiperone (1 microM), two drugs that bind to cortical 5-hydroxytryptamine2 receptors in the rat brain. Furthermore, the pattern of hippocampal [3H]spiperone binding differed considerably from that of 5-[3H]hydroxytryptamine. The [3H]ketanserin binding in the hippocampal region did not exceed background levels, except in the hilus of area dentata in the ventral hippocampus and entorhinal layer VI at the same level, where moderate binding was found.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1984

Studies on the mechanism of action of substituted benzamide drugs.

The effects of classical neuroleptic drugs (haloperidol, chlorpromazine) and atypical neuroleptics, i.e. substituted benzamides (L-sulpiride, tiapride, FLA 731(-] on specific in vivo binding of the dopamine antagonist 3H-spiperone and the dopamine agonist 3H-n-propylnorapomorphine (3H-NPA) was examined in male rats. The atypical neuroleptics were found to be considerably more potent in displacing nigral than striatal 3H-spiperone binding while the classical neuroleptics were about equipotent in the two brain regions. The benzamides also produced considerably less displacement of 3H-spiperone in the striatum than did classical neuroleptics. Furthermore, while the classical neuroleptic drugs block the striatal 3H-spiperone and 3H-NPA binding sites to about the same degree, the substituted benzamides appear to have a higher affinity for the DA receptors labelled by 3H-NPA than those labelled by 3H-spiperone. The behavioural effects of the benzamides were found to differ from classical neuroleptic drugs particularly with regard to induction of catalepsy. Thus, the induction of cataleptic behaviour was found to correlate with displacement of 3H-spiperone in the striatum while blockade of apomorphine induced hyperactivity correlated with the displacement of spiperone in extrastriatal areas.

Animals↗

PubMed1984

The importance of the peripeduncular nucleus in the neuroendocrine control of sexual behavior and milk ejection in the rat.

Electrocoagulations situated in the lateral midbrain tegmentum cause severe deficits in sexual behavior and lactational performance of rats. In this study we determined the extent to which these effects could be reproduced by axon-sparing lesions using the excitotoxin, ibotenic acid; in another group of rats, 6-OHDA was infused in the same area to degenerate the mesencephalic catecholamine neuronal elements affected by the electrocoagulations. It was found that ibotenic acid, but not 6-OHDA, reproduced most of the effects produced by electrolytic lesions. Thus, female rats bearing ibotenic acid lesions showed little sexual receptivity and proceptivity in response to estrogen and progestin treatment, and the milk ejection reflex appeared nonfunctional following the lesion. Ibotenic acid-infused male rats failed to ejaculate on most postoperative observations, though they continued to mount he estrous female. Examination of the lesions with immunohistochemical visualization of tyrosine-hydroxylase- and substance P-positive neurons, and thionine staining, revealed that the neurotoxins exhibited the intended selectivity, though the ibotenic acid lesions were associated with loss of substance P-immunoreactive nerve terminals in the substantia nigra and the peripeduncular region. It is suggested that the peripeduncular nucleus plays an important role in the neuroendocrine control of male and female copulatory behavior, as well as in the regulation of the milk ejection reflex.

Animals↗

PubMed1983

A morphological analysis of vasoactive intestinal polypeptide (VIP)-like immunoreactive neurons in the area dentata of the rat brain.

The general distribution and morphology of vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) neurons in the area dentata (AD) have been studied using immunohistochemical methods on thick (70-120 micron) sections from the rat brain. The long (greater than or equal to 72 hours) incubation of free-floating sections in combination with a sensitive immunoperoxidase method resulted in extensive labeling of VIP-positive cell bodies, along with their dendritic and axonal processes in the hippocampal formation, including the area dentata. The VIP-positive cells are found in all parts of the area dentata, and plots of the distribution of individual cells showed that there is a preferential clustering of these neurons within, or in close proximity to, the granule cell layer, while the deep zones in the hilus are almost completely devoid of VIP-LI immunoreactive neurons. Throughout the long axis of the AD the number and relative position of the VIP-LI neurons remains rather constant. Analysis of the size and shape of the VIP-positive neurons in the AD shows a remarkable morphological heterogeneity, with the soma ranging from small (long axis: approximately 10 micron) ovoid or round, to large (long axis: approximately 25 micron) stellate or multipolar; of these the small to medium sized cells predominate. Comparisons between the morphology of neurons visualized with the VIP antibody and sections stained by the rapid Golgi method allow a rather conclusive classification of some of the VIP-stained neurons, while the classification of a majority of the VIP neurons remains tentative, perhaps because of the selective visualization by the rapid Golgi method of only certain cell types in the AD. On the basis of this comparison, several displaced granule cells in the molecular layer, as well as granule cells, small ovoid cells, and pyramidal basket cells in the granule cell layer have been identified as VIP-positive as determined by their somatic shape, dendritic branching pattern, and axonal projections. In addition, several VIP-positive neurons have been identified with less certainty. These include the dentate basket cell of Cajal, certain small cells in the molecular layer, and fusiform cells in the polymorph layer. Taken together the present results demonstrate the usefulness of "Golgi-like" immunoperoxidase staining for detailed classification of chemically defined neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗