Biomedical subjects
Publications and source records attributed to D M Armstrong.
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Extracellular recordings have been obtained from individual motor cortical neurones of cats walking along a horizontal ladder. We present responses obtained when selected rungs dropped unexpectedly by a small amount beneath the animal's weight. Our results show that forelimb motor cortex is rapidly and in graded fashion informed of such events, which may produce appreciable changes in impulse activity in the corticospinal tract.
Although it is well known that magnocellular cholinergic basal forebrain neurons are trophically responsive to nerve growth factor (NGF) and contain NGF receptors (NGFr), the exact distribution of forebrain NGFr-immunoreactive neurons and the degree to which cholinergic neurons are colocalized with them have remained in question. In this study we employed a very sensitive double-labelling method and examined in the same tissue section the distribution and cellular features of NGFr-positive and choline acetyltransferase (ChAT)-immunolabelled neurons within the rat basal forebrain. Throughout this region the majority of magnocellular basal forebrain neurons were immunoreactive for both NGFr and ChAT. However, a small percentage of neurons in the ventral portion of the vertical limb of the diagonal band of Broca were immunoreactive only for NGFr, whereas a larger population of magnocellular neurons in the substantia innominata exhibited only ChAT immunoreactivity. No NGFr-immunoreactive cells were found associated with ChAT-positive neurons in the striatum, neocortex, or hippocampus, and no single-labelled NGFr-immunoreactive neurons were found outside the basal forebrain area, except for a large number of positive-labelled cells along the ventricular walls of the third ventricle. In addition to its function in maintaining the normal integrity of the basal forebrain and cholinergic, peripheral sympathetic, and neural-crest-derived sensory neurons, NGF may also have a role in the growth of these neurons after damage to the nervous system. To examine this postulate the hippocampus was denervated of its septal input and examined 8 weeks later. Two populations of neurons were found to have undergone collateral sprouting--namely, the midline magnocellular cholinergic neurons of the dorsal hippocampus and the sympathetic noradrenergic neurons of the superior cervical ganglion. Both of these neuronal populations also stained strongly for NGFr. In contrast, the small intrinsic cholinergic neurons of the hippocampus exhibited neither sprouting response nor staining for NGFr. In view of these results, we suggest that the differing sprouting responses demonstrated by these three neuronal populations may be due to their responsiveness to NGF, as indicated by the presence or absence of NGF receptors.
A hybrid microdrive is described, comprising remote stepper motors connected by a hydraulic link to a slave electrode positioner which is light enough for use with freely walking cats. The system provides 18 mm of electrode movement in 2 or 10 microns steps.
In recent years the present authors and others have sought to determine the neurochemical composition of the dilated neuronal processes found within neuritic plaques of patients with Alzheimer's disease. To date a number of neurotransmitter and neuropeptide systems have been observed within different plaques, yet at present it is unclear whether individual human plaques contain more than one transmitter substance. In the present study a highly sensitive dual-immunolabeling procedure was employed and it was demonstrated that substance P and somatostatin-immunoreactive profiles coexist within single senile plaques of patients with Alzheimer's disease. Coexistence of somatostatin and substance P immunoreactivity within plaques was observed in the hippocampus and amygdala but not in the neocortex, although the latter region contained plaques within which somatostatin and substance P existed alone. The frequency with which we observed one or more neuropeptide within plaques was relatively low and in fact most plaques contained neither substance P nor somatostatin immunoreactivity. In addition, a large number of swollen peptidergic processes were observed outside of plaques. The significance of these observations with respect to the pathogenesis of Alzheimer's disease is discussed.
In this study we determined that cholinergic neurons from the lateral dorsal tegmental (LDT) and peribrachial pontine region (PPG) innervate the medial pontine reticular formation (medial PRF), a region involved in the generation of REM sleep. Wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the medial PRF and the brainstem tissue was processed using a combined retrograde transport/immunocytochemical procedure. Results showed that 10-15% of choline acetyltransferase (ChAT) immunoreactive neurons in the LDT and PPG project to the medial PRF. It is hypothesized that these neurons play an important role in the generation of the REM sleep state.
The distribution and morphologic characteristics of choline acetyltransferase (ChAT)-containing neurons were studied throughout the rostrocaudal extent of the rat hippocampus and in a midline area just dorsal to the dorsal hippocampus. Peroxidase reaction product was observed with the aid of immunohistochemical methods and a high-titer polyclonal antibody against ChAT, the acetylcholine biosynthetic enzyme. ChAT-positive cells in the hippocampus were characterized by small, round or oval perikarya with two or more proximal processes. They were located within the caudal and temporal hippocampal formation, predominantly within the subiculum, in the stratum lacunosum moleculare, at the border of the stratum lacunosum moleculare and the stratum radiatum, and in the molecular layer of the dentate gyrus. The cells resembled in morphology the small, bipolar and multipolar neocortical ChAT-immunoreactive cells. In addition to the hippocampus, ChAT-positive neurons were observed caudally in a region just above the dorsal hippocampal commissure and rostrally in the columns of the fornix. These cells were large with an oval perikarya and darkly labeled compared to neurons in the hippocampus. They more closely resembled the ChAT-positive neurons in the midline raphe of the medial septal nucleus. Examination of the rat hippocampus 2 and 8 weeks following unilateral lesioning of the fimbria-fornix and supracallosal striae revealed a sparse innervation of ChAT-positive fibers in the hippocampus ipsilateral to the lesion. ChAT-labeled neurons in the hippocampus did not appear to sprout in response to the lesion. In contrast, ChAT-positive cells in the midline did appear to sprout into the medial dorsal subiculum and dorsal medial hippocampus. We conclude that these two populations of cells are distinct with respect to their response to hippocampal denervation and, furthermore, that this distinction may be attributed to a differential response to nerve growth factor.
Septal efferent fibers from the neurons in the medial septal nucleus are destroyed by fimbria-fornix aspirative lesion. In the present study we used quantitative morphometric techniques to evaluate the response of these axotomized septal neurons to a constant infusion of nerve growth factor (NGF). By 2 weeks following the lesion, approximately 75% of the cholinergic neurons had degenerated in the untreated rats. The remaining cholinergic neurons showed few signs of the effect of the lesion when stained for a polyclonal antibody to ChAT and examined in 40-micron-thick sections. In 1-micron-thick sections the remaining ChAT-immunoreactive (IR) neurons also appeared no different from the intact ChAT neurons. However, non-ChAT-IR neurons had a shrunken nucleus, while all other morphometric parameters appeared normal. NGF infusion protected most of the ChAT-IR neurons from degenerating. The saved neurons had the same parameters as the undamaged ChAT-IR neurons when examined in either 40-micron- or 1-micron-thick sections. In addition, the shrunken appearance of the non-ChAT-IR neurons' nuclei was avoided by the NGF infusions. Enlarged ChAT-IR processes were evident in the dorsolateral quadrant of the septum following damage to the fimbria-fornix. NGF-infusions prevented the formation of these processes. Instead, in the treated animals the dorsal lateral quadrant contained a dense plexus of fine ChAT-IR varicosities. Taken together these results demonstrate that NGF not only can protect the cholinergic neurons from axotomy-induced degeneration but can also cause the saved neurons to maintain the same morphometric appearance as intact ChAT-IR neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunocytochemistry was used to establish the cellular localization of choline acetyltransferase [ChAT] throughout the rostrocaudal portions of the nuclei of the solitary tracts [NTS] in rat brain. By light microscopy, two distinct populations of ChAT-positive cells were identified. The first consisted of relatively few, medium-sized neurons located in the caudal one-half of the medial NTS just dorsal to the dorsal motor nucleus of the vagus. The second population of ChAT-labeled neurons was located more anteriorly and surrounded the medial and dorsal borders of the tractus solitarius. These cells were more abundant and smaller diameter than those located more caudally. Thick, non-varicose processes with the light microscopic characteristics of dendrites also were selectively labeled for ChAT. A few of these processes were located near or were continuous with the labeled perikarya of the NTS. However, the vast majority of the immunoreactive processes could be traced from ChAT-labeled perikarya in the ventrally adjacent dorsal motor nucleus of the vagus. These dorsally directed dendrites aborized extensively throughout the NTS, but they were densest in the rostral two-thirds of the nucleus. Caudally, the labeled dendrites coursed horizontally, forming a commissure-like structure between the two vagal motor nuclei. Electron microscopy confirmed the perikaryal and dendritic localization of ChAT in the NTS. The perikarya were characterized by dense peroxidase immunoreactivity throughout the cytoplasm, infolded nuclear membranes, and somatic synapses. The labeled dendritic profiles also were intensely immunoreactive and received synaptic input from unlabeled terminals. The unlabeled afferents to somata and dendrites contained large populations of small clear vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)
Damage to the fimbria-fornix, and separately to the perforant path, leads to distinct and dramatic time-dependent increases in glial fibrillary acidic protein immunoreactivity (GFAP-IR) in specific areas of the hippocampal formation. Specifically, fimbria-fornix lesions resulted in an increase in the GFAP-IR in the pyramidal and oriens area of the CA3 as well as the inner molecular layer of the dentate gyrus. In addition, in the septum ipsilateral to the lesion, there was a rapid and robust increase in GFAP-IR in the dorsal lateral quadrant of the septum, but not in the medial region. Only after 30 days did the GFAP-IR reach the medial septum. Following perforant path lesions, there was a selective increase in GFAP-IR in the outer molecular layer of the dentate gyrus. Most of these changes were transient and had disappeared by 30 days postlesion. We speculate that the increase in GFAP-IR in these target areas is a necessary requirement for the sprouting responses that are observed. This hypothesis is supported by the fact that astrocytes secrete NGF in vitro and that NGF activity increases in these target areas following these same lesions. A mechanism for the selective activation of the astrocytes through the initial activation of microglia and secretion of interleukin-1 is postulated.
Electroencephalographic activity of the neocortex was evaluated in young (5-7 months) and aged (26-28 months) rats. All animals in the aged group showed behavioral impairment in a spatial task (water maze). A neocortical electroencephalogram was derived simultaneously from 16 different neocortical locations and was subjected to spectral analysis. The frequency of occurrence and duration of high-voltage spindles was determined in two sessions, each involving a total of 30 min alert immobility. Changes in spectral characteristics and high-voltage spindles in response to scopolamine administration were also evaluated. The power of high-frequency activity (8-20 Hz) was significantly reduced in the aged subjects. This was greatest in the temporo-occipital regions, while no significant changes were seen in the mediofrontal region. Scopolamine resulted in a large power increase in all frequency bands, but the increase in the higher-frequency range (8-20 Hz) was significantly less in the aged group. The incidence of high-voltage spindles was 6 times higher and their total duration was 9 times longer in aged rats, with virtually no overlap with the young group. In young rats, scopolamine increased the incidence and total duration of high-voltage spindles, while it decreased both parameters in the aged subjects. Cholinergic neurons in the nucleus basalis appeared shrunken in the aged animals. These findings demonstrate that reliable electroencephalographic changes are present in the neocortex of the aged rat, and that some of the physiological alterations may be due to the pathological changes in the cholinergic nucleus basalis.
In the present study we examined the distribution of cholinergic and catecholaminergic neurons, in the feline brainstem, as defined by choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) immunohistochemistry. In the dorsal tegmentum, ChAT immunoreactive neurons were distributed in the parabrachial area [the pedunculopontine group (PPG)] and along the medial adjacent central gray [the lateral dorsal tegmental group (LDT)]. The cholinergic neurons in the LDT area were larger than those in the PPG. When adjacent tissue sections were labeled with TH we noted extensive overlap between catecholamine and cholinergic neurons in the PPG, suggesting that REM sleep may occur as a result of an interaction between these transmitters in this area rather than the medial pontine reticular formation where no cholinergic or catecholamine neurons were found. Cholinergic neurons were also found in the cranial nerve nuclei and the nucleus ambiguus. The presence of cholinergic neurons in the PPG and LDT suggest that these neurons may play an important role in the generation of some of the tonic and phasic components of REM sleep, such as cortical desynchronization, pontogeniculo occipital waves, and muscle atonia.
1. The temporal pattern of the discharge of complex spikes by Purkinje cells in the paravermal cortex of the cerebellar lobule V b/c has been examined during locomotion in awake cats. 2. The peripheral receptive fields of 138 Purkinje cells were examined using light tactile stimulation. In 91% of these cells, complex spikes were evoked by stimuli applied to the ipsilateral forelimb and of eighty-eight cells examined in most detail, 76% had receptive fields including the paw or wrist. Sixty-six per cent had receptive fields restricted to the paw and/or wrist. 3. Complex spikes were not discharged at rigidly fixed times during the step cycle in any of sixty-nine Purkinje cells which were recorded during locomotion on a moving belt. 4. When the discharges were averaged over many steps the probability of occurrence of complex spikes showed small fluctuations during the course of the step cycle, but these fluctuations were shown not to be statistically significantly different from those which could arise by chance. 5. These findings are inconsistent with previous suggestions (e.g. Armstrong, 1974; Rushmer, Roberts & Augter, 1976) that, during locomotion, the climbing fibres act to signal the occurrence of specific peripheral events, such as foot touch-down or lift-off.
1. Extracellular microelectrodes were used in free-to-move cats to study the locomotor-related discharges of Purkinje cells in the intermediate part of lobule V of the cerebellar anterior lobe and of neurones in the underlying nucleus interpositus anterior. All cells studied discharged rhythmically during locomotion. 2. The discharges during walking at a speed of 0.5 m/s on a horizontal exercise belt were compared with those during (a) walking at 0.9 m/s (when the duration of the step cycle is shortened considerably and the amplitudes of the locomotor electromyograms (EMGs) recorded from flexor and extensor muscles of the limbs are markedly increased) and (b) during walking at 0.5 m/s with the belt tilted uphill by 30 deg (when step duration is little changed but locomotor EMGs are increased by 70-100%). 3. In each of thirty Purkinje cells the timing of the discharges relative to the forelimb step cycle showed no major difference between the two speeds of walking. Most cells discharged at slightly higher overall rates at the faster walking speed but the increase was usually modest, the average being only 5.6 impulses/s (i.e. an increase of 8%). Peak rates sometimes underwent larger increases but the average was only 11.9 impulses/s (+11%). Changes in minimum rate were generally small (an average increase of 0.3 impulses/s). 4. Among twenty-one interpositus neurones there was only one in which discharge timing relative to the step cycle was different between the two speeds. Like the Purkinje cells, most neurones discharged slightly faster at the higher speed but the average increase was only 5.5 impulses/s (+8.5%). Peak firing rates also usually showed a modest increase (averaging 6.2 impulses/s; +6.5%) while minimum rates were little changed. 5. Among nineteen Purkinje cells compared between walking uphill and on the flat only one showed any major difference in discharge phasing; overall firing rates were on average only 1.3 impulses/s (2%) higher for uphill locomotion. 6. Among twenty-one interpositus neurones discharge phasing differed markedly between walking uphill and on the flat in only two cells. Overall discharge rates were on average slightly higher uphill (by 3.5 impulses/s; 6.7%) and peak rates also usually increased slightly (on average, by 6 impulses/s; 7.7%). Minimum rates were higher, on average, by 1.6 impulses/s (+5%). 7. The findings are discussed in relation to current notions of how the intermediate part of the cerebellum may contribute to movement control and it is concluded that the neurones studies probably make little contribution to determining the vigour of the movements of steady walking.
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Lesions of the rat nucleus basalis magnocellularis (nBM) result in a marked decrease in cortical choline acetyltransferase (CAT) and in behavioral deficits. After unilateral ibotenic acid (IBO) lesions of the nBM in rats, there was a significant ipsilateral loss of frontal and parietal CAT, which did not recover for 3 months following surgery and was accompanied by a loss of CAT immunoreactivity in the peripallidal region. Bilateral ibotenate nBM lesions resulted in a marked deficit of one-trial step-through passive avoidance (PA) at 24 hours. Cholinesterase inhibitors including physostigmine, N-ethylaklylphenyl carbamate (RA-6), and N,N-methylethylphenyl carbamate (RA-7) were administered in separate experiments, for 2 days before retrieval testing or for 3 consecutive days during consolidation immediately following training. Nonsignificant improvements in PA latency were produced using 0.32 mg/kg physostigmine and 2.5 mg/kg RA-6 administered before retrieval testing. The results suggest that destruction of cholinergic neurons in the nBM are involved in the PA deficit, but does not exclude the possibility that damage to other neuronal systems may contribute to the observed behavioral deficit.
Recent anatomical investigations of the mammalian neostriatum have uncovered discrete neurochemical zones characterized by low levels of AChE and high levels of enkephalin-like immunoreactivity (ELI) compared with the surrounding neostriatal tissue. These regions, termed striosomes, which appear as patches in individual sections, have been associated with specific afferent and efferent pathways that differ from those of the surrounding neostriatal tissue. In the present study, the 3-dimensional distribution of these enkephalin-rich compartments in the caudate nucleus of the adult cat was investigated using computer-assisted 3-dimensional reconstruction techniques. Series consisting of coronal, sagittal, and horizontal tissue sections were obtained. In individual sections, discrete patches of intense enkephalin-like immunoreactivity appeared against a lighter-staining background. Three-dimensional reconstructions revealed that these patches overlapped across sections to form a highly inter-connected structure within the head and body of the caudate nucleus. Several structural features were evident in these reconstructions that appeared to be similar across animals. One consistent pattern was the formation of enkephalin-labeled finger-like structures radiating from the ventricular edge diagonally across the width of the nucleus. Smaller crossbridges were seen connecting the fingers, which often resulted in the formation of claws or rings of enkephalin-like immunoreactivity. These elements appear to align across planes to form a lattice-like structure outlining continuous regions of matrix. This structure may provide a basis for the orderly interaction between the patch and matrix compartments.
In the present study we employed immunohistochemical techniques using a polyclonal antibody against choline acetyltransferase (ChAT) to determine the distribution and cytological features of cholinergic neurons in the developing septal/diagonal band complex of the rat. ChAT-positive perikarya were first clearly detected in this region on embryonic day 17, although the neurons were faintly labeled and lacked the cytological details found in the adult. After birth we observed a dramatic increase in the intensity of the immunolabeling which continued until postnatal day 23. Thereafter, the ChAT-positive neurons assumed their adult-like characteristics.