Biomedical subjects

R A Code

Publications and source records attributed to R A Code.

29 records · Page 2Linked to original sources

PubMed1989

Development of GABA immunoreactivity in brainstem auditory nuclei of the chick: ontogeny of gradients in terminal staining.

The development of gamma-aminobutyric acid-immunoreactivity (GABA-I) in nucleus magnocellularis (NM) and nucleus laminaris (NL) of the chick was studied by using an antiserum to GABA. In posthatch chicks, GABA-I is localized to small, round punctate structures in the neuropil and surrounding nerve cell bodies. Electron microscopic immunocytochemistry demonstrates that these puncta make synaptic contact with neuronal cell bodies in NM; thus, they are believed to be axon terminals. GABAergic terminals are distributed in a gradient of increasing density from the rostromedial to the caudolateral regions of NM. The distribution of GABA-I was studied during embryonic development. At embryonic days (E) 9-11, there is little GABA-I staining in either NM or NL. Around E12-14, a few fibers are immunopositive but no gradient is seen. More GABA-I structures are present at E14-15. They are reminiscent of axons with varicosities along their length, preterminal axonal thickenings and fiber plexuses. At E15, terminals become apparent circumscribing neuronal somata and are also discernible in the neuropil of both nuclei. In E16-17 embryos, terminals are the predominantly labeled GABA-I structures and they are uniformly distributed throughout NM. The density of GABAergic terminals increases in caudolateral regions of NM such that by E17-19, there is a gradient of increasing density of GABA-I terminals from the rostromedial to caudolateral regions of NM. The steepness of this gradient increases during development and is the greatest in posthatch (P) chicks. Cell bodies labeled with the GABA antiserum are located around the borders of both NM and NL and in the neuropil between these two nuclei. Occasionally, GABA-I neurons can be found within these auditory brainstem nuclei in both embryonic and posthatch chicks. Nucleus angularis (NA) contains some GABAergic cells. The appearance of GABA-I terminals around E15 is correlated in time with the formation of end-bulbs of Held on NM neurons. Thus, the ontogeny of presumed inhibitory inputs to chick auditory brainstem nuclei temporally correlates with, and could modulate the development of, excitatory auditory afferent structure and function.

Aging↗

PubMed1989

Glycine-immunoreactivity in the auditory brain stem of the chick.

Glycine-immunoreactivity (Gly-I) was studied in the auditory brain stem of chick using a polyclonal antiserum to glycine conjugated to bovine serum albumin (Wenthold et al., 1987). During embryonic development, little Gly-I is present in nucleus magnocellularis (NM), nucleus laminaris (NL), or nucleus angularis (NA). In posthatch chicks, a few Gly-I terminals are found on nerve cell bodies in NM. Gly-labeled terminals are rare in NL and NA. When present in NL, they appear to be apposed to neuronal somata and not to dendrites. Occasionally, a Gly-labeled cell can be found in NM. After unilateral cochlea removal, Gly-labeled terminals are still present in NM. Thus, the cochlea does not appear to be the source of the glycinergic afferents to NM. The pattern of staining of Gly-I contrasts sharply with that of gamma-aminobutyric acid-immunoreactivity (GABA-I). The number of Gly-I terminals in NM, NL and NA appears to be much less than that of GABA-I. In addition, GABA-I terminals are very abundant around both the cell bodies and dendrites of neurons in NM and NL, whereas Gly-I terminals are found only on neuronal somata. Gly-I in NM also appears to be much less than that in its mammalian homologue, the anteroventral cochlear nucleus.

Animals↗

PubMed1989

Studies on the discriminative stimulus properties of apomorphine in rhesus monkeys.

Four rhesus monkeys were trained to discriminate the effect of apomorphine (0.1 mg/kg IM) from that of saline injections. The discriminative stimulus (DS) effect of apomorphine generalized to the dopamine D2 receptor agonist quinpirole. The D1 dopamine receptor agonist SKF 38393 elicited responses only on the saline-appropriate lever. Stimulus generalization of the dopamine autoreceptor agonist 3-PPP exhibited stereospecificity favoring the (+) over the (-) isomer. d-Amphetamine, phencyclidine, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and clonidine did not share the DS effect of apomorphine. The D2-selective antagonists sulpiride and metoclopramide reversed both the DS effect and the response rate reduction produced by the training dose of apomorphine. Chlorpromazine and the D1 antagonist Sch 23390 also antagonized the DS effect, but the antagonism was accompanied by a further rate reduction. Haloperidol and clozapine antagonized the DS effect incompletely. The DS effect produced by apomorphine in this study appears to be mediated predominantly by post-synaptic D2 receptor activation, with contribution also from the D1 receptor.

Animals↗

PubMed1987

Some transforming growth factor-alpha connections and their colocalization with enkephalin in the rat central nervous system.

Transforming growth factor alpha (TGF alpha) has been immunocytochemically localized in neuronal perikarya throughout the adult rat central nervous system (CNS). In order to determine if any TGF alpha-immunoreactive (TGF alpha-I) cell bodies have long axonal projections, indirect immunofluorescence was used in combination with injections of the fluorescent retrograde tracer, Fluoro-Gold (FG). Both TGF alpha-I and retrogradely transported FG were found within the same neurons in the interpeduncular nucleus (IPN) after bilateral FG injections in the dorsal tegmental nucleus (DTg). Neurons that contain both TGF alpha-I and FG were also found in the raphe magnus, raphe obscurus, raphe pallidus and the gigantocellularis reticular nuclei after FG injections in the upper thoracic spinal cord. Cell bodies double-labeled with TGF alpha-I and FG were found in the dorsal parabrachial nucleus (DPB) following FG injections in the central nucleus of the amygdala (Ce). In addition, Leu-enkephalin immunoreactivity (L-ENK-I) was colocalized with TGF alpha-I in the same projection neurons after the injections described above. These results suggest that cells that contain TGF and the opioid peptide, L-ENK, have long projections in the rat CNS, and that, due to their co-localization within the same neurons, they may exert their effects concomitantly.

Animals↗

PubMed1986

Columnar organization and reciprocity of commissural connections in cat primary auditory cortex (AI).

The laminar distribution and reciprocity of commissural axon terminals and cells of origin in cat primary auditory cortex (AI) were studied after injections of tritiated proline combined with horseradish peroxidase in the middle ectosylvian gyrus. Terminal fields were found in every cortical layer in the contralateral AI, and they were characterized quantitatively. The largest concentration of silver grains was in layer III (about 25% of the total number of silver grains) and, to a lesser extent, in layers V, VI, and I (some 18% of the total in each layer). The labeling in layer I was concentrated in its deeper half, while the labeling in the other layers was more homogeneous. Layer IV had the least labeling, followed by layer II, each receiving about 10% of the total. The labeling was always heaviest over the neuropil and lightest over neuronal perikarya. Commissural terminal fields formed radial patches oriented perpendicularly to the pia, and averaging 543 micron in width. There was consistently three times more silver grains in a patch than in an inter-patch area. However, the number of silver grains in an inter-patch area was always significantly above background, indicating a possible commissural projection to these zones as well. The patches of commissural terminal fields formed bands oriented across AI and running in a caudoventral to rostrodorsal direction. Strict reciprocity between the commissural cells of origin and terminal fields was not found at the light microscopic level when adjacent sections, corrected for differential shrinkage, were compared. Often, patches of terminal fields were free of retrogradely labeled cells and, conversely, there were patches of labeled cells without an overlying commissural terminal field. The terminal fields connected homotopic regions of the contralateral AI, and every region of AI received commissural innervation, unlike the primary somatic sensory and visual cortex, where large zones receive only a few commissural afferents. The more complete pattern of interhemispheric connectivity in auditory cortex is in contrast to the less continuous commissural representation in other sensory neocortical fields. Perhaps this pattern contributes to the anatomical representation of binaurality in auditory cortex.

Animals↗

PubMed1985

Commissural neurons in layer III of cat primary auditory cortex (AI): pyramidal and non-pyramidal cell input.

The types of layer III neurons in cat primary auditory cortex (AI) projecting to the contralateral AI were studied with horseradish peroxidase or horseradish peroxidase conjugated to wheat germ agglutinin. Injections between the anterior and posterior ectosylvian sulci retrogradely labeled both pyramidal and non-pyramidal somata in contralateral cortical layers III, V, and VI in AI, and in the ventral nucleus of the ipsilateral medial geniculate body. Three-quarters (72%) of the retrogradely labeled cells were found in layer III and one-quarter (28%) lay in layers V and VI. Every part of AI was innervated by commissural neurons. The topographical distribution of the labeled cells varied systematically. Injections in the caudal part of AI labeled cells in the caudal part of the opposite AI, while more rostral injections labeled cells in the contralateral, rostral AI. Injections covering the rostro-caudal extent of AI labeled cells throughout the opposite AI. Each part of AI thus projects most strongly to a contralateral, homotypic area, and less strongly to other, adjacent sectors of AI. The types of labeled cells were distinguished from one another on the basis of size, somatic and dendritic morphology, laminar distribution, and nuclear membrane morphology. Their somatodendritic profiles were compared to, and correlated with, those in Golgi-impregnated material from adult animals. Among the pyramidal cells of origin were small, medium-sized, and large neurons, and star pyramidal cells. The non-pyramidal cells of origin included bipolar and multipolar cells. Thus, at least six of the 12 kinds of neurons, as defined by morphological methods, participate in the interhemispheric pathway. Pyramidal cells comprised 65% of the cells of origin, 14% of the labeled cells in layer III were non-pyramidal, and 21% of the neurons could not be classified. It is unknown if these different types of commissural neurons have the same laminar or cytological targets in AI, or if they represent more than one functional or parallel pathway within AI. In any case, cytologically diverse layer III neurons contribute to the commissural system.

Animals↗

PubMed1984

Phencyclidine-like behavioral effects of 2-methyl-3,3-diphenyl-3-propanolamine (2-MDP).

2-Methyl-3,3-diphenyl-3-propanolamine (2-MDP) produced effects in animals similar to those produced by the dissociative anesthetics such as phencyclidine (PCP). Specifically, it shared the discriminative stimulus properties of PCP in rats trained to discriminate PCP (1 mg/kg) from saline; at higher doses, it disrupted brightness discrimination and stimulated locomotor activities in rats trained to avoid shocks in an automated Y-maze; and it produced surgical anesthesia when injected IV to rhesus monkeys. These pharmacological activities were observed only with the levo-isomer of 2-MDP. The dextro-isomer was either inactive or produced opposite effects, depending on the tests. Among several related diphenylpropylamines, 2-MDP represents the optimal structure for potency of PCP-like effects since changes in the amino, 2-methyl and 3-hydroxy groups reduced the potencies of the PCP-like discriminative properties.

Anesthesia↗

PubMed1983

Absorption of triazolam from pelleted drug-diet mixtures by the mouse: quantitation of alpha-hydroxytriazolam in urine.

The absorption of triazolam from pelleted drug-diet mixtures by mice under steady-state conditions was determined for doses up to 150 mg/kg/day by measuring alpha-hydroxytriazolam, the principal urinary metabolite of triazolam in the mouse, in urine samples collected over a 24-hour period. Following beta-glucuronide glucuronosohydrolase hydrolysis of the urine, quantitation of alpha-hydroxytriazolam was accomplished using a specific reverse-phase liquid chromatographic method which utilized UV detection at 214 nm. Assay precision was greater than 2.7% (CV) over the concentration range of interest. Statistical analysis of the excretion data indicated that the mathematical relationship between the triazolam dose and the quantity of alpha-hydroxytriazolam excreted was linear for female mice and nonlinear for male mice. Triazolam absorption, as reflected by alpha-hydroxytriazolam urinary excretion data, increased with triazolam dose.

Animals↗

PubMed1983

Discriminative stimulus properties of nalorphine in the rhesus monkeys.

The discriminative stimulus properties of nalorphine were studied in rhesus monkeys trained to discriminate i.m. injections of nalorphine (1 mg/kg) from saline. During training, a two-lever paradigm was employed where a single, 3-min extinction schedule was followed by fixed-ratio-20 schedules of food presentation. During the fixed-rate schedules, responses on one of the two levers produced food when nalorphine had been administered and responses on the other lever produced food when saline had been administered. During stimulus generalization tests, responses on either lever produced food under the fixed-ratio schedule. The discriminative stimulus effects of nalorphine were antagonized by naloxone which, by itself, did not generalize to nalorphine. The kappa opiate agonists, ethylketocyclazocine, U-50,488, bremazocine, tifluadom, as well as two mixed kappa-sigma agonists, dl-cyclazocine and dl-N-allylnormetazocine (SKF-10047), generalized to nalorphine with the following potency ranking order: bremazocine greater than ethylketocyclazocine greater than tifluadom greater than cyclazocine greater than U-50,488 greater than N-allylnormetazocine greater than nalorphine. The levo-isomers of cyclazocine, N-allylnormetazocine or U-50,488 generalized to nalorphine whereas the dextroisomers did not. Generalization to nalorphine did not occur with the mu opiate agonists, morphine, methadone and meperidine, or the nonopiate compounds, phencyclidine, ketamine and chlorpromazine. The results suggest that a kappa opiate receptor mechanism mediates the discriminative effects of nalorphine in the rhesus monkey, which may also be involved with the naloxone-sensitive, sedative and dysphoric effects of nalorphine in humans.

Animals↗

PubMedDate not supplied

Some projections of dynorphin-immunoreactive neurons in the rat central nervous system.

Dynorphin 1-8 (DYN 1-8) and Dynorphin B (DYN B) have been immunocytochemically localized to neuronal perikarya throughout the adult rat central nervous system (CNS). In order to determine if any DYN 1-8 and DYN B immunoreactive (DYN-I) cell bodies have long projections, indirect immunofluorescence was used in combination with injections of the fluorescent retrograde tracer, Fluoro-Gold (FG). Both DYN-I and retrogradely transported FG were found within the same neurons in the dorsal parabrachial nucleus (DPB) after FG injections in the central nucleus of the amygdala (Ce). Neurons that contain both DYN-I and FG were also found in the paraventricular nucleus, the perifornical region, the dorsal area and the lateral hypothalamus after FG injections in the upper thoracic spinal cord. These results suggest that cells that contain DYN-I have long ascending and descending projections in the rat CNS, and thus may exert widespread effects.

Animals↗

PubMedDate not supplied

Development of cat somatosensory cortex: structural and metabolic considerations.

Although research is beginning to clarify the relationship between structure and functional activity in the adult cerebral cortex, little is known about cortical development in the somatosensory cortex of cats. A number of parameters were used in this study to identify functional and anatomical correlates in the developing somatosensory cortex of kittens ranging in age from 3 to 33 d: 2-deoxyglucose (2DG) uptake, cytochrome oxidase (CO) activity, Nissl staining, and AChE activity. All of these parameters were found to reflect an immaturity that evolved to the adult-like pattern by 4-5 weeks of age. Nissl staining revealed an immature laminar pattern at birth, in which layers I, V, and VI were distinct whereas layers II-IV were homogeneous in appearance. Numerous cells could be observed at the layer VI-white matter junction and throughout the white matter, a feature not found in adults. The laminar distribution of Nissl-stained cells gradually became mature by 4-5 weeks of age. CO staining was homogeneous throughout all layers, in contrast to the adult pattern, which displays laminar differentiation. In young animals, many darkly stained CO+ cells were found at the layer VI-white matter border and in the white matter, a distribution not found in the adult. AChE staining in kittens was also distinctly different from that in adults. At birth, AChE+ fibers could be found in layers I, V, and VI but were scarce in layers II-IV. In the adult, a dense network of AChE+ fibers can be found in all layers. 2DG uptake was also immature, as little stimulus-evoked activity could be observed in animals younger than 2 weeks. A dense band of metabolic activity was found in the zone between layer VI and the white matter, whether or not a somatic stimulus was delivered. These results suggest a close correlation between the developing cytoarchitecture and the emergence of a mature pattern of functional activity in the somatosensory cortex.

Acetylcholinesterase↗