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Biomedical subjects

D A Godfrey

Publications and source records attributed to D A Godfrey.

At least 73 records · Page 4Linked to original sources

Aspartate aminotransferase activity in fiber tracts of the rat brain.

Activity of aspartate aminotransferase, an enzyme which catalyzes the interconversion of the excitatory transmitter candidates, glutamate and aspartate, has been measured in fiber tracts of rat, with an emphasis on sensory and motor systems of the brain. Most tracts had significantly higher activities than the cholinergic facial nerve root, consistent with the possibility that a component of aspartate aminotransferase activity might serve as a marker for neurons using glutamate and/or aspartate as neurotransmitter. Highest activity was in the auditory nerve root. On the other hand, a close correlation was found between aspartate aminotransferase and malate dehydrogenase activities in the fiber tracts, raising the question whether aspartate aminotransferase activity may be more closely related to energy metabolism than to transmitter metabolism.

Animals↗

Effects of large brain stem lesions on the cholinergic system in the rat cochlear nucleus.

Large lesions were made medial to one cochlear nucleus in rats, in order to cut virtually centrifugal pathways to it. To estimate the contribution of these centrifugal pathways to cholinergic synapses in the cochlear nucleus, choline acetyltransferase and acetylcholinesterase activities were mapped, by quantitative histochemical procedures, in lesion and control side cochlear nuclei. Choline acetyltransferase activities were reduced by 85-90% in most regions of the lesion side cochlear nucleus and by 65-75% in granular regions. Acetylcholinesterase activities were reduced by 50% or less in the same regions. The choline acetyltransferase results are consistent with a conclusion that by far most cholinergic synapses in the rat cochlear nucleus derive from centrifugal pathways. Additionally, the effects of the lesions on enzyme activities in the lateral superior olivary nucleus and ventral nucleus of the trapezoid body, and in the facial, motor trigeminal, and spinal trigeminal nuclei were examined. In the lesion side facial nucleus, 60% and 40% decreases in choline acetyltransferase and acetylcholinesterase activities, respectively, were apparently consequences of facial root transection. Lesion-control enzyme activity differences in the other nuclei were much smaller.

Acetylcholinesterase↗

Isolation and chemical analysis of neuron soma samples from the cat cochlear nucleus.

Pieces of neuron somata were dissected from the cochlear nuclei of two cats and analyzed for activity of malic dehydrogenase, an important enzyme of oxidative metabolism. Based on location, size and shape the somata were identified as those of spherical bushy cells, octopus cells, and fusiform cells. Somata of cerebellar Purkinje cells were analyzed for comparison. The results suggest that the large cochlear nucleus neurons have malic dehydrogenase activities higher than those of most other neurons so far studied. Also, the octopus and fusiform somata had higher malic dehydrogenase activities than those of the spherical bushy cells.

Animals↗

Regional distributions of choline acetyltransferase and acetylcholinesterase activities in layers of rat cerebellar vermis.

Entire sagittal sections of rat cerebellar vermis were dissected into microgram-sized samples of molecular, granular, and white matter layers. Assayed activities of choline acetyltransferase and acetylcholinesterase were plotted back onto sectional maps of exact sample locations. On the average, the activities of choline acetyltransferase and acetylcholinesterase in the granular layer were about four and five times, respectively, those in the molecular layer. The highest activity of both enzymes was in the granular layer of the vestibulocerebellum, the nodulus and ventral uvula (lobules X and IXc of Larsell). This activity might be related to the secondary vestibulocerebellar projection, terminating as mossy fibers in the granular layer of this region. Intermediate levels of activity were found in the granular layer of the dorsal uvula (lobule IX, a and b). The lowest activities of both enzymes in the granular layer were in the culmen (lobule V). A 7.1-fold difference in choline acetyltransferase activity and a 4.5-fold difference in acetylcholinesterase activity were found between the granular layer of lobules V and X. The numerical density of aggregates of acetylcholinesterase staining product in the granular layer correlated much better with assayed acetylcholinesterase activity than with choline acetyltransferase activity.

Acetylcholinesterase↗

Distribution of myo-inositol in the cat cochlear nucleus.

The distribution of myo-inositol, a substance that has been implicated in synaptic transmission, has been mapped within sections of the cat cochlear nucleus as well as some nearby regions. Highest values in the cochlear nucleus were found in regions of granule cells along the periphery of the anteroventral subdivision of the nucleus. Highest values overall were found in the molecular layer of the cerebellar flocculus. A fairly good correlation was found between myo-inositol levels and activities of the enzymes of acetylcholine metabolism in the cat cochlear nucleus, supporting the possibility that myo-inositol may be involved in cholinergic synaptic transmission. No positive correlation was found between myo-inositol levels and the levels of glutamate, aspartate, glycine, or gamma-aminobutyric acid (GABA). The most striking gradient of myo-inositol levels within a region was found in the auditory nerve, where different myo-inositol levels might be related to nerve fibers innervating different parts of the cochlea. The distribution of scyllo-inositol, a stereoisomer of myo-inositol, was also examined, and found to parallel closely the distribution of myo-inositol, with levels 4--5% as high.

Acetylcholinesterase↗

Quantitative distribution of choline acetyltransferase and acetylcholinesterase activities in the rat cochlear nucleus.

Within the cochlear nucleus of the rat, as well as some nearby regions, quantitative histochemical mapping procedures were used to construct maps of the distributions of choline acetyltransferase and acetylcholinesterase activities. The results were in some ways consistent with results previously reported for cat, e.g., very low activities of both enzymes were found in the auditory nerve root, and also in the vestibular nerve root, except where acetylcholinesterase-positive centrifugal fibers are located, very high activities were found in the facial nerve system. In many ways, however, the results for the rat cochlear nucleus contrasted with those for the cat. Notably, choline acetyltransferase activities in some regions of the rat cochlear nucleus were as much as 30- to 60-fold higher than for the comparable regions in the cat, and both enzymes had much more uniform distributions in the rat cochlear nucleus than in the cat. The more prominent cholinergic system in the rat cochlear nucleus might relate to a proportionately larger population of cholinergic interneurons, or, more probably, a more significant innervation by cholinergic, centrifugal pathways, or both, as well as, perhaps, generally higher choline acetyltransferase activities in cholinergic neurons of rat.

Acetylcholinesterase↗

Effect of intervening lesions on amino acid distributions in rat olfactory cortex and olfactory bulb.

Levels of the proposed neurotransmitter amino acids glutamate, aspartate, gamma-aminobutyric acid (GABA), and glycine were measured within the layered structures of the olfactory bulb and olfactory cortex following unilateral transections of the lateral olfactory tract or of virtually all fiber tracts of the olfactory peduncle. Distributions of the amino acids on both lesion and control sides were examined and compared by means of a mapping procedure. The results suggest: 1) Glutamate and aspartate are specifically associated with mitral (and presumably also tufted) cell axons and terminals in the piriform cortex. The distribution of aspartate in the olfactory bulb is further suggestive of a specific association of aspartate with mitral cell dendrites and somata. 2) Glutamate might be specifically associated with some centrifugal fibers traveling to the olfactory bulb in or near the anterior commissure. 3) GABA might be specifically related to some certrifugal fibers to the olfactory bulb in addition to its prominent association with granule cells of the bulb. 4) Glycine is unlikely to play a prominent neurotransmitter role in either the olfactory bulb or olfactory cortex.

Amino Acids↗

Distribution of gamma-aminobutyric acid, glycine, glutamate and aspartate in the cochlear nucleus of the rat.

The distributions of gamma-aminobutyric acid (GABA), glycine, glutamate and aspartate were measured in cochlear nuclei of two rats by quantitative histochemical mapping procedures. The levels and distributions in the two rats were comparable, and resembled those previously reported for cat cochlear nucleus. The results are consistent with a concept that these putative transmitter amino acids have similar levels and distributions in the cochlear nucleus among mammals.

Aminobutyrates↗

Quantitative histochemical studies of the hypothalamus enzymes of acetylcholine metabolism.

The quantitative histochemical distribution of acetylcholinesterase and choline acetyltransferase activity has been measured in individual hypothalamic nuclei and median eminence, as well as in entire hypothalamic sections by a mapping technique. There was an 18-fold range of nuclear choline acetyltransferase activity with highest activities in the lateral preoptic nucleus and median eminence. There was a nine-fold range of nuclear acetylcholinesterase activity with highest activities in the lateral preoptic and magnocellular nuclei and lowest activity in the median eminence. The substantial gradients of choline acetyltransferase activity found in the hypothalamus indicate the importance of using a technique that provides an objective, permanent record of contiguous sample locations thereby allowing detailed analysis of tissue areas using, but not dependent on, anatomical boundaries.

Acetylcholinesterase↗

Approach to three-dimensional mapping of quantitative histochemical measurements applied to studies of the cochlear nucleus.

After reviewing the historical development of some procedures for localizing quantitative histochemical measurements, an approach is presented which combines some aspects of these procedures to make possible a permanent, objective record of the location of each sample. The method further allows direct comparisons to be made with drawings of other nearby sections during the process of sampling. Illustrations are given of various applications to a study of the cochlear nucleus. A particular benefit of the approach is to facilitate comparison of chemical with anatomical and physiologic data.

Acetylcholinesterase↗

A block model of the cat cochlear nucleus.

A three-dimensional block model of the cochlear nucleus of the cat was constructed from histologic sections. Boundaries of various subdivisions, based on cytoarchitectonic criteria, were included in the model. Usage of the block model in correlating physiological and anatomical data is illustrated by localizing characteristic waveforms of gross evoked responses and characteristic frequencies of single units.

Animals↗

Single unit activity in the posteroventral cochlear nucleus of the cat.

Single unit activity in the posteroventral cochlear nucleus (PVCN) was recorded for a variety of stimulus conditions. The units were classified according to their response characteristics. The locations of units were plotted onto a three-dimensional block model of the cochlear nucleus. Certain types of units that responded best to the onsets of stimuli were located predominantly in the octopus cell region of the PVCN. The remainder of the PVCN, which contains a rather heterogeneous collection of small and multipolar cells, was found to contain several types of units with the dominant type being "chopper" units.

Acoustic Stimulation↗

Single unit activity in the dorsal cochlear nucleus of the cat.

Single unit activity was examined in three component layers of the dorsal cochlear nucleus (DCN): the molecular layer, the fusiform cell layer, and the polymorphic layer (deep DCN). Electrophysiological units were classified into types on the basis of their activity under a variety of stimulus conditions. In the molecular layer spike activity was small and difficult to isolate. Almost all units in the fusiform cell layer could be classified as either "pauser" or "buildup" units. Classification of units in the deep DCN was sometimes difficult, but "pauser," "chopper," and some "on" units were found. The "on" types of units tended to be located in the more superficial part of the deep DCN. Unit locations were referred to a three-dimensional block model of the cochlear nucleus.

Acoustic Stimulation↗