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E C Azmitia

Publications and source records attributed to E C Azmitia.

At least 109 records · Page 6Linked to original sources

Atlas of serotonergic cell bodies in the cat brainstem: an immunocytochemical analysis.

The localization and relative number of serotonergic (5HT) cell bodies in the brainstem of the cat were studied through the use of a specific immunocytochemical technique. A surprisingly large number of 5HT cells were found in regions in addition to the classical raphe nuclei (obscurus, pallidus, magnus, centralis superior, and dorsalis). Foremost among these were: the ventral medulla, just dorsal to the pyramidal tract and inferior olivary complex, and especially the area in and around the lateral reticular nucleus; the dorsal pons, surrounding the central reticular core, and in the central gray area; and a region in the mesencephalon, in and around the interpeduncular nucleus. The advantages and disadvantages of the existing schemas for subdividing and labeling groups of brain 5HT neurons are discussed.

Animals↗

Age differences in within-session habituation of exploratory behavior: effects of stimulus complexity.

The effects of age on the habituation of exploratory behavior of 8-month- and 28-month-old male C57BL/NNia mice were examined under three different stimulus complexity conditions. Increases in the degree of stimulus complexity resulted in an attenuation of between-session habituation and an initial disruption of within-session habituation by 8-month-old mice. Although increases in stimulus complexity also resulted in an increase in the overall level of exploration by aged mice, stimulus complexity was not found to have a systematic effect on between- or within-session habituation by aged mice. No between-session habituation was observed in aged mice under any of the stimulus complexity conditions. Further, aged mice exhibited significant within-session increases, rather than decreases, in exploration under each stimulus complexity condition. This disruption of within-session habituation in aged mice was found to persist over four daily test sessions. In view of the specific patterns of exploration by aged mice, the disruption of within-session habituation was attributed to age-related differences in reactivity to the arousal-inducing properties of novel stimuli.

Aging↗

Interactions between hippocampal serotonin and the pituitary-adrenal axis in the septal driving of hippocampal theta-rhythm.

Stimulation of the septal area at a frequency between 6 and 10 Hz is able to drive hippocampal theta. In freely moving male rats, the minimum threshold current for driving theta occurs at 7.7 Hz. Disruption of the pituitary-adrenal axis by injection of corticosterone to normal rats or by bilateral adrenalectomy (ADX) causes a shift of the minimum theta-driving threshold to 6.9 Hz. Corticosterone injection to ADX rats returns the minimum to 7.7 Hz. Specific and localized removal of hippocampal serotonergic fibers by intracerebral injections of 5,7-dihydroxytryptamine (5,7-DHT) produces the same shift to a 6.9-Hz minimum threshold as does corticosterone or ADX. We further report that these effects of manipulating the adrenocortical and serotonergic systems act through related (or common) mechanisms since: (1) 5,7-DHT shift to 6.9 Hz can be reversed to 7.7 Hz by injection of corticosterone; (2) 5,7-DHT lesions in an ADX rat produce a normal theta threshold minimum at 7.7 Hz, and (3) in a combined ADX- and 5,7-DHT-lesioned rat, corticosterone again produces a 6.9-Hz minimum as this hormone does in normal rats. These results suggest that the serotonergic inputs to the hippocampus interact with the same neurons which concentrate corticosterone.

Adrenalectomy↗

Evidence for the presence of serotonergic perikarya in the fetal rat pancreas as demonstrated by the high affinity uptake of [3H] 5-HT.

Evidence has been obtained for the presence of serotonergic fibers in the adult rat pancreas; however, the location of the serotonergic cell bodies remains unknown. Fetal rat pancreata (18, 20 and 22 days) were demonstrated to possess a high-affinity uptake of serotonin. Radioautography revealed the uptake sites to be similar to those seen in the adult, indicating the presence of serotonergic fibers in early development. In addition, cell bodies, possibly representing primitive neurons, were demonstrated to be heavily labelled. This suggests a possible intra-pancreatic location for the cell bodies of the pancreatic nerves. The preservation of the specific serotonin uptake in 18-day fetal tissue after 4 days in organ culture substantiates this view.

Animals↗

Formation of a glial scar following microinjection of fetal neurons into the hippocampus or midbrain of the adult rat: an immunocytochemical study.

Raphe tissue (minced or dissociated) from fetal rat was microinjected into adult hippocampus or midbrain, and the response of astrocytes observed by immunocytochemical staining for the astrocyte specific marker, glial fibrillary acidic protein (GFA). Astrocytes were observed to form a border around the transplanted cells. This border was visible as early as 7 days post-transplant and was still present up to 6 months later. The transplanted serotonergic cells, identified by immunocytochemical staining with a primary antibody to serotonin, appeared at the edge of the border but not beyond. This border may be responsible for preventing the complete integration of the transplanted cells with the adult host hippocampal and midbrain tissue.

Animals↗

Effects of 5,7-dihydroxytryptamine on HRP retrograde transport from hippocampus to midbrain raphe nuclei in the rat.

The combination of horseradish peroxidase (HRP) retrograde tracing and specific lesioning using 5,7-dihydroxytryptamine (5,7-DHT) was applied to the midbrain raphe-hippocampal system. Serotonergic fibers from the median raphe nucleus (MRN) of the rat reach the dorsal hippocampus (HIPP) through the cingulum bundle (CB) and the fornix-fimbria (FF). Intracerebral microinjections of 5,7-DHT in these two bundles were made at various times before HRP injections into the dorsal HIPP. After both CB and FF lesion, the number of labeled cells in MRN is reduced to 49.6% at zero time (HRP injected immediately after 5,7-DHT) and to 6.5% after 2 days. There was no significant effect on the number of labeled cells in the locus ceruleus. Selective lesioning of 5-HT fibers in the CB or the FF revealed that raphe-CB-HIPP neurons and raphe-FF-HIPP neurons have a similar distribution pattern in the MRN, but that a dorsal group of neurons at the junction of MRN and dorsal raphe nucleus took the CB route exclusively to innervate the HIPP. The CB pathway was used by more neurons (55% of total number of labeled neurons) than was the FF (21%). An appreciable number of fibers (23%) appear to have branches in both pathways. Our findings are discussed with regard to the recovery of HIPP function seen after long term destruction of 5-HT fibers in the CB.

5,7-Dihydroxytryptamine↗

Effects of microinjections of 5,7-dihydroxytryptamine in the suprachiasmatic nuclei of the rat on serotonin reuptake and the circadian variation of corticosterone levels.

The role of the 5-hydroxytryptamine (5-HT) terminals in the suprachiasmatic nucleus (SCN) in the production of the circadian variation of corticosterone secretion was investigated by lesioning the 5-HT inputs to the SCN with 5,7-dihydroxytryptamine (5,7-DHT). Vehicle-injected animals showed a normal circadian variation of corticosterone levels. In contrast, the mean corticosterone levels of the 5,7-DHT-lesioned group were intermediate between control peak and trough values, and although the individual rats showed fluctuations, no significant circadian variation was present in the group as a whole. 3H-5-HT reuptake in the SCN was reduced to 38% of the mean control level in the 5,7-DHT-lesioned group, but ventromedial hypothalamic 3H-5-HT reuptake was only decreased to 82% of control. These results indicated that the SCN 5-HT terminals may play an important role in the synchronization of the circadian variation of corticosterone secretion.

5,7-Dihydroxytryptamine↗

Effect of 5-HT depletion of the hippocampus on neuronal transmission from perforant path through dentate gyrus.

Stimulation of the perforant pathway (pp) elicits a characteristic evoked action potential (EAP) in the granule cell layer of the dentate gyrus. The EAP was recorded in rats depleted of hippocampal serotonin (5-HT) by prior injection of p-chloroamphetamine (PCA) or 5,7-dihydroxy-tryptamine (5,7-DHT) as well as in untreated animals during two behavioral states, slow-wave sleep (SWS) and still-alert behavior (SAL). As reported previously, in untreated rats the amplitude of the EAP response was significantly greater during SWS than SAL. Stimulation of the median raphe nucleus (MR) prior to stimulating the pp (prestimulation) augmented the EAP response, but only during SWS. In contrast, in animals injected with PCA or 5,7-DHT there was no difference of the amplitude of the EAP during SWS and SAL. However, the augmentation of the EAP during SWS produced by prestimulation of the median raphe was still present. It is concluded that 5-HT innervation of the dentate gyrus may be involved in the behavioral modulation of the EAP response. Modulation of the EAP following prestimulation of the MR appears to be effected by a non-serotonergic input to the dentate gyrus originating in, or coursing through, the median raphe.

5,7-Dihydroxytryptamine↗

Physiological stimulation enhances HRP marking of salivary neurons in rats.

Neurons of the superior salivary nucleus in rats have been labeled by retrograde transport of HRP injected into the lingual nerve. The nucleus is formed by a band of small, multipolar cells diagonally oriented in the lateral reticular formation of the caudal pons, just caudal to the root of the facial nerve. As time for transport of HRP was increased from 14 1/2 to 24 hr, the number of labeled cells increased exponentially along the curve, Y = 0.001 exp(0.51T), r = 0.995, to a maximum of 272 cells. Stimulating neuronal activity immediately after HRP injection, by swabbing the rat's mouth with 1% acetic acid, increased the number of labeled cells at 14 1/2 (p less than 0.05), 16, 18 and 20 (p less than 0.01) hr transport time. Counts of labeled cells in stimulated animals fell along a cumulative, normal distribution curve (ogive) with a mean at 18.2 hrs, S.D. 1.6 hr. Enhanced labeling of activated cells could be due to more rapid transport rates or to increased amounts of HRP transported.

Afferent Pathways↗

Specific in vitro uptake of serotonin by cells in the anterior pituitary of the rat.

In vivo studies have suggested that serotonin (5HT) influences anterior pituitary function at the hypothalamic level. The present in vitro study investigated the possibility that 5HT may act directly on the anterior pituitary. The high affinity uptake of [3H]5HT into adult rat anterior pituitary tissue was examined in two types of experiments. 1) To test the specificity and saturability of uptake of 5HT in the anterior pituitary, pituitary tissue was incubated (37 C) with [3H]5HT (10(-8)-10(-6) M) in the presence and absence of excess (10(-5) M) unlabeled 5HT, norepinephrine, fluoxetine (FLUOX), metergoline, or cyproheptadine. A Hofstee analysis of the specific uptake of [3H]5HT gave an apparent Km value of 4.23 x 10(-7) M and a Vmax of 1576 pmol/g/10 min [3H]5HT. The total uptake of [3H]5HT was not altered by norepinephrine or metergoline, but was significantly reduced (P less than 0.01-0.001) by FLUOX and cyproheptadine. Uptake was shown to be temperature and sodium dependent and not directly dependent on energy derived from glycolysis or aerobic metabolism. 2) To study the site of uptake of 5 HT in the anterior pituitary, in concomitant radioautographic experiments, tissue was incubated with [3H]5HT with and without excess 5HT or FLUOX. Three patterns of silver grain distribution were observed: 1) nonrandom concentrations over select anterior pituitary cells near blood vessels, 2) heavy aggregates of silver grains usually associated with blood vessels, and 3) a seemingly random dispersal of grains over pituitary tissue. Tissue incubated with [3H]5HT alone contained 10% heavily labeled cells, 32% moderately labeled cells, and 58% weakly labeled cells. In contrast, no heavily labeled cells were seen when tissue was incubated with either excess 5HT or FLUOX in addition to [3H]5HT. Our findings of saturable and specific high affinity uptake of [3H]5HT into a subgroup of anterior pituitary cells suggest a direct pituitary action of 5HT.

Animals↗

Bilateral serotonergic projections to the dorsal hippocampus of the rat: simultaneous localization of 3H-5HT and HRP after retrograde transport.

Horseradish peroxidase (HRP, Sigma VI, 30-70 nl of a 10-15% solution in saline) or 3H-5HT (30 Ci/mmole, 2.5 X 10 -3 M containing 3.3 X 10(-3) M norepinephrine in saline, 50-100 nl) was injected unilaterally into the dorsal hippocampus in separate groups of rats. HRP-labeled cells were seen in the hippocampus, medial septal nucleus, nucleus of the diagonal band, supramammilary nucleus, median raphe nucleus, interfascicular portion of the dorsal raphe nucleus, and the locus coeruleus. In contrast, 3H-5HT-labeled cells were largely restricted to the raphe nuclei. In this nucleus an equal number of ipsilateral and bilateral cells were found. Occasionally, these labeled cells stretched across the midline (bridge pattern). In another series, the 3H-5HT and HRP were injected into the same hippocampus either as a mixture or sequentially. This resulted in double labeling of the median and dorsal raphe neurons. A final group of rats received injections of 3H-5HT and HRP into opposing hippocampi. Double-labeled cells accounted for 10% of the neurons labeled. In addition, closely paired neurons composed of an HRP- and 3H-5HT-containing cell were found. In summary, the serotonergic fibers may play a key role in harmonizing the electrical activity of the hippocampi by use of bilateral projections, paired neurons with differential projections, and bridging neurons stretching across the midline but with unilateral projections.

Animals↗

The immunocytochemical localization of serotonergic neurons in the rat hypothalamus.

In rats pretreated with pargyline and L-tryptophan a group of neurons in the dorsomedial hypothalamus stained immunocytochemically for serotonin. These neurons measured approximately 9 micrometer and were distributed over a rostro-caudal distance of 900 micrometer. There were a total of 708 cells. No labeled cells were seen in this hypothalamic group in normal, colchicine- or pargyline-pretreated rats.

Animals↗

Hippocampal serotonin re-uptake and nocturnal locomotor activity after microinjections of 5,7-DHT in the fornix-fimbria.

The role of the hippocampal 5-hydroxytryptamine (5-HT) terminals in the control of locomotor activity was investigated by lesioning 5-HT axons in the fimbria with 5,7-dihydroxytryptamine (5,7-DHT). Rats pretreated with desimipramine (10 mg/kg, i.p.) received microinjections of 5,7-DHT (0, 1, 3, 5 or 10 micrograms in 0.4 microliter ascorbic Ringer's solution) into the fornix-fimbria. On the fourteenth to twenty-first nights after operation, nocturnal locomotor activity was measured in photocell cages. Twenty-eight to thirty days after operation degeneration of 5-HT terminals was assessed by measuring in vitro [3H]5-HT re-uptake in slices of dorsal hippocampus, ventral hippocampus and the septum. Groups injected with 5,7-DHT showed hyperactivity in the night period and increased decrements of activity between tests, both of which were related to the dose of neurotoxin. A reduction of [3H]5-HT re-uptake was found in dorsal hippocampus which was related to the dose of 5,7-DHT), but ventral hippocampal and septal [3H]5-HT re-uptake were not systematically reduced. For each rat, levels of dorsal and ventral hippocampal [3H]5-HT re-uptake were negatively correlated with the mean nocturnal activity from the 7 nights of testing. Levels of dorsal, but not ventral hippocampal [3H]5-HT re-uptake were negatively correlated with the mean nightly decrement of activity. No correlations were found between septal [3H]5-HT and these activity measures. These results, indicate that the increase in nocturnal locomotor activity caused by generalized depletion of 5-HT in the brain may be due to disruption of hippocampal 5-HT terminals supplied by the fornix-fimbria.

5,7-Dihydroxytryptamine↗

Fetal raphe and hippocampal transplants into adult and aged C57BL/6N mice: a preliminary immunocytochemical study.

Fetal mouse raphe and hippocampal tissue (from embryos with crown-rump length (CRL) 13-16 mm) was transplanted into adult and aged isogenetic mice to study the growth of serotonergic fibers between host and donor tissue. A specific antibody against serotonin (5-HT) was used to immunocytochemically visualize 5-HT containing cell bodies and fibers. Unilateral fetal transplants into the hippocampi of adult (4-6 mo.) or aged (24 mo.) mice matured and sent out processes which very densely innervated the transplant tissue itself and extended into the host hippocampus. The termination of these fibers was consistent with the known 5-HT-hippocampal lamination pattern in normal animals. Qualitative comparisons suggested that the density of outgrowth into adult hippocampus was greater than into aged hippocampus. Conversely, adult 5-HT neurons send sprouts into fetal hippocampal tissue transplanted into the lateral ventricle. Therefore, immunocytochemical procedures can be used to monitor outgrowth from the fetal tissue to the host and ingrowth from the adult host to the fetal tissue. Furthermore, the apparent normal 5-HT lamination pattern produced by fetal raphe axons in adult hippocampus is consistent with reports that neuronal transplantation is effective in reversing the anatomical and behavioral deficits produced by homotypic denervation of a terminal field.

Age Factors↗