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Biomedical subjects

J H Haring

Publications and source records attributed to J H Haring.

33 records · Page 2Linked to original sources

Changes in the noradrenergic innervation of the area dentata after axotomy of coeruleohippocampal projections or unilateral lesion of the locus coeruleus.

Lesions of the septal region result in a significant decrease in the norepinephrine content of the area dentata. Over a period of one year, norepinephrine levels return to normal, presumably due to the proliferation of remaining locus coeruleus fibers. Unilateral lesions of the locus coeruleus produce reductions in [3H]norepinephrine uptake values of about 70% and 30% in the ipsilateral and contralateral area dentata, respectively. By 12 weeks after lesion, the noradrenergic fiber density in the contralateral area dentata is within the range of control measurements, whereas the area dentata ipsilateral to the lesion remains significantly depleted of noradrenergic fibers. At 26 weeks postlesion, no further change was observed in the noradrenergic fiber density of either area dentata. These results are interpreted in light of the hypothesis that locus coeruleus axon proliferation is induced by axotomy and represents the expansion of intact collaterals of damaged fibers.

Animals↗

The identification of some sources of afferent input to the rat nucleus basalis magnocellularis by retrograde transport of horseradish peroxidase.

Neurons of the nucleus basalis magnocellularis (NBm) of the rat are contained within the ventromedial globus pallidus and adjacent internal capsule. Horseradish peroxidase injection limited to the ventromedial globus pallidus result in sparse neuronal labeling in a variety of brainstem, thalamic and hypothalamic nuclei, and the basal nuclei identified after NBm injections. Thus, these contiguous regions have comparable subcortical inputs. By contrast, only NBm injections yielded a large number of labeled neurons in layer V of NBm cholinergic neurons. in addition to the reciprocity observed between NBm and frontal cortex, the ventral tegmental area and NBm likewise appear to be reciprocally connected.

Afferent Pathways↗

Peripheral sympathetic ingrowth can alter metabolic activity within the hippocampal formation.

After cholinergic denervation of the hippocampal formation, peripheral sympathetic fibers arising from the superior cervical ganglia grow into the dentate gyrus and CA3 region; the functional significance of sympathetic ingrowth into the hippocampal formation is unknown. Utilizing electrical stimulation of the preganglionic trunk in combination with 2-deoxy-D-[3H]-glucose fine-grained autoradiograms, we demonstrated an alteration of hippocampal glucose metabolism, suggesting that this neuronal rearrangement makes functional connections within the hippocampus.

Animals↗

Retrograde labeling of locus coeruleus neurons after lesion-induced sprouting of the coeruleohippocampal projection.

Locus coeruleus axons have been observed to proliferate and reinnervate targets after the partial removal of normal locus coeruleus inputs. Sixteen weeks after a large electrolytic lesion of the septal region, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections of the dorsal area dentata resulted in the labeling of neurons of the dorsal half of the locus coeruleus. Similar injections made at earlier postlesion times failed to produce visible HRP labeling in the locus coeruleus. These observations are consistent with our previous report of the time course for the noradrenergic reinnervation of the dorsal area dentata after septal lesions. Using double-labeling techniques, we have also demonstrated that collaterals of locus coeruleus axons that originally innervated the dorsal area dentata sprout to reinnervate that region 4 months after a lesion of the septal region. Thus the homotypic compensatory proliferation of locus coeruleus projections appears to be mediated, at least in part, by a pruning effect.

Animals↗

Differential distribution of locus coeruleus projections to the hippocampal formation: anatomical and biochemical evidence.

Locus coeruleus (LC) fibers in the fornix mainly innervate the septal pole of the dentate gyrus, whereas the cingulum projects to the ventral hippocampal formation to provide LC input to the dentate gyrus. LC fibers in the ventral amygdaloid bundle have a wide-spread distribution, innervating the entire hippocampal gyrus, as well as the mid-septotemporal and temporal regions of the dentate gyrus. The LC fibers of the fornix and ventral amygdaloid bundle do not appear to overlap significantly in the septal pole of the dentate gyrus.

Amygdala↗

Response properties of raccoon cuneothalamic neurons.

Microelectrodes were used to record the extracellular activity of 80 single neurons of the main cuneate nucleus (MCN) of raccoons anesthetized with either methoxyflurane or pentobarbital sodium. All 80 MCN neurons had peripheral receptive fields (RFs) that lay entirely on the glabrous surfaces of the forepaw and were responsive to light mechanical stimulation. Neurons were characterized according to the nature of their response to mechanical stimulation of their RFs, as well as to their response to electrical stimulation of the contralateral thalamic ventrobasal complex (VB). All antidromically activated neurons (64% of sample) were histologically verified as falling within the clusters region of the MCN, while synaptically activated neurons (19% of sample), as well as neurons not responsive to VB stimulation (17% of sample), were located in both the clusters and the polymorphic regions. Antidromically activated neurons typically responded with a single fixed-latency spike, although a few responded with a burst of 3 or more spikes. Others responded with a single antidromic spike followed by a train of synaptically activated spikes. In these latter neurons, it was often possible to block the synaptic spikes selectively. MCN neurons were classed according to their response to controlled mechanical stimuli as rapidly adapting (RA), slowly adapting (SA), or Pacinian (Pc). The proportions of neurons falling into these categories did not vary significantly with the type of response to thalamic stimulation, and the overall percentages were 56% RA, 24% SA, and 20% Pc. These figures are very similar to those previously obtained in a sample of primary afferent fibers of the raccoon cervical cuneate fasciculus (L. M. Pubols and Pubols, 1973). Absolute displacement, displacement velocity, and force thresholds, which ranged between 4 and 326 micron, 0.01 and 16.3 micron/msec, and 120 and 3600 mg, respectively, are comparable to those previously found for primary afferents supplying mechanoreceptors of the glabrous surfaces of the raccoon's forepaw. Neither displacement nor force thresholds differed for RA versus SA neurons; however, displacement velocity thresholds were significantly lower for SA than for RA neurons.

Afferent Pathways↗

Distribution of cerebellar mossy fibers arising from neurons of the raccoon main cuneate nucleus.

The present study demonstrates that fibers originating in the raccoon main cuneate nucleus are not segregated in specific cortical regions of target cerebellar folia as reported in studies of the cat cuneocerebellar tract. This observation supports the hypothesis that exteroceptive and proprioceptive divisions of the raccoon cuneocerebellar tract do not exist as distinct structural entities. The findings of this study do not preclude the possibility that projections from the external and main cuneate nuclei are segregated within the cerebellar cortex on the basis of functional modality rather than nucleus of origin.

Animals↗

Topography of neurons of the raccoon main cuneate nucleus with projections to the inferior colliculus.

The origin of the projection from the raccoon main cuneate nucleus to the inferior colliculus has been demonstrated by means of retrograde transport of horseradish peroxidase. Neurons of the polymorphic division of the main cuneate nucleus project to the inferior colliculus via the medial lemniscus. Neurons projecting to the inferior colliculus are only found caudal to the obex and do not overlap significantly with the distribution of cuneocerebellar neurons as in the cat.

Animals↗

Facilitated reversal learning of a spatial-memory task by medial septal injections of 6-hydroxydopamine.

To assess the role of hippocampal norepinephrine in learning and memory, rats were treated with medial septal injections of 6-hydroxydopamine either prior to or after acquisition of a spatial-memory task. No effect on acquisition learning or retention was observed. However, reversal learning was significantly enhanced in all treated animals regardless of whether treatment was prior to or after acquisition. Our results do not support a role of hippocampal norepinephrine in selective attention, but rather indicate a direct involvement in memory processes.

Animals↗

Electrophysiology of raccoon cuneocerebellar neurons.

Electrophysiological experiments were undertaken in order to locate and functionally characterize cells of the raccoon main cuneate nucleus (MCN) that can be activated by electrical stimulation of the cerebellum. A total of 98 such units were studied in pentobarbital sodium-anesthetized, methoxyflurane-anesthetized, or decerebrate preparations. Aside from a greater likelihood of resting discharge in the decerebrate preparations, no appreciable variability in physiological properties of the neurons could be attributed to differences in the type of preparation. Using constant latency of response and ability to be blocked by collision as principal criteria, both antidromically (n = 31) and synaptically (n = 67) activated neurons of the main cuneate nucleus could be identified. A small number of MCN neurons could be activated by both cerebellar and thalamic stimulation, but no unit was antidromically activated from both locations. MCN neurons projecting to the cerebellum are located primarily in the ventral polymorphic cell region of the nucleus at and rostral to the obex, corresponding to the "medial tongue" region of Johnson et al. (1968). In contrast, neurons synaptically activated from the cerebellum are found throughout the dorsoventral extent of the rostral MCN, including the "clusters" region. The majority of antidromically activated units responded to mechanical stimulation of deeper tissues, and most of these were activated by muscle stretch. Only a small portion (13-15%) of either antidromically or synaptically activated units were classed as light touch units with peripheral receptive fields (RFs) restricted to glabrous surfaces of the forepaw. Glabrous skin RFs located on the digital surfaces are smaller than those located on the palm pads. In both cases, RFs are larger than those associated with primary afferent fibers, but toward the low end of the distribution for MCN neurons not activated by cerebellar stimulation. All MCN units activated by cerebellar stimulation, regardless of modality, respond to mechanical stimulation with trains of irregularly spaced single spikes. Glabrous skin cutaneous mechanoreceptive MCN neurons, whether rapidly or slowly adapting, respond to ramp indentations with an instantaneous frequency which may be described as a power function of ramp velocity, with exponents less than one. These values are in the same range as those previously reported for primary afferents of the cuneate fasciculus (Pubols and Pubols, 1973).

Adaptation, Physiological↗

Acetylcholinesterase neurons in the lateral hypothalamus project to the spinal cord.

The possibility that cholinergic neurons of the basal forebrain project to the spinal cord was investigated utilizing the retrograde transport of bisbenzimide and [3H]choline as well as acetylcholinesterase histochemistry. A striking similarity was observed in the distributions of lateral hypothalamic neurons labeled with bisbenzimide and acetylcholinesterase. Only a small number of these neurons contained both markers, suggesting the possibility of a small cholinergic projection from the lateral hypothalamus to the spinal cord. The use of [3H]choline to test this hypothesis yielded negative results. Thus the present observations indicating that lateral hypothalamic neurons are cholinoceptive, are consistent with choline acetylcholinesterase immunohistochemical studies. The potential for basal forebrain cholinergic neurons to influence spinal autonomic activity via the lateral hypothalamus is discussed.

Acetylcholinesterase↗

Topography of locus ceruleus neurons projecting to the area dentata.

The distribution of locus ceruleus neurons projecting to the dorsal and ventral area dentata was studied using the retrograde transport of horseradish peroxidase (HRP). Furthermore, the possibility that collaterals of single locus ceruleus neurons innervate both the dorsal and ventral area dentata was explored with a retrograde double-label technique using HRP and the fluorescent dye 4',6-diamidino-2-phenylindole 2 HCl (DAPI). Fusiform and multipolar neurons of the pars dorsalis of the locus ceruleus (LCd) were labeled after injection of HRP into the area dentata. The HRP-positive cells were found almost exclusively in the dorsal LCd after dorsal area dentata injections whereas ventral injections labeled neurons throughout the LCd. The highest density of LCd neurons labeled from the ventral area dentata was observed in the dorsal half of the LCd and thus overlapped with the distribution of neurons labeled from dorsal injections. Neurons containing both HRP and DAPI were observed in the dorsal LCd suggesting that the topographic coincidence of neurons labeled from dorsal and ventral area dentata was in part a result of single neurons having terminals in both loci.

Animals↗

A horseradish peroxidase study of projections from the main and external cuneate nuclei to the cerebellum of the North American raccoon.

Neurons of the raccoon main (MCN) and external (ECN) cuneate nuclei having terminal fields in the anterior lobe and paramedian lobule of the cerebellum were studied by means of the retrograde transport of horseradish peroxidase (HRP). In the MCN, neurons of the polymorphic regions, but not of the round cell clusters, were labeled following HRP injections of the anterior lobe. HRP-labeled fusiform, triangular, and stellate cells were observed from 3-4 mm caudal to the obex to 2-3 mm rostral to it. The main body of labeled MCN neurons was located in the 1.25 mm immediately rostral to the obex, there forming a recognizable subnucleus in the ventral MCN. The ECN displayed uniform labelling from the anterior lobe with no particular cell type or nuclear region being labeled preferentially. A minor projection to the anterior lobe appeared to originate in the contralateral MCN and ECN. Injections of the paramedian lobule produced MCN labeling similar to that observed after anterior lobe injections, but the majority of labeled ECN neurons were found in the dorsomedial part of the nucleus. In lobule V of the anterior lobe, sagittal zone c contained the greatest density of cuneocerebellar terminals as judged by the degree of retrograde labeling seen in neurons of both the MCN and ECN. This observation was consistent with evoked potentials recorded in the anterior lobe of the raccoon cerebellum. The position of cuneocerebellar neurons in the ventrolateral MCN suggests that the bulk of the information being transferred to the cerebellum by the raccoon MCN is related to deep, rather than cutaneous, modalities.

Animals↗

Protargol silver impregnation and neuronal selectivity. Light and electron microscopic observations.

The neuronal selectivity of protargol silver was determined in embedded and cultured nervous tissue by light (LM) and transmission electron microscopy (TEM). Ultrastructurally, silver (85-140 A in diameter) was found deposited in neuronal, but not glial, perikarya and cell processes. Usually, the silver grains were arranged in elongated arrays that were associated with electron-dense, strand-like structures that correspond to the 'neurofibrils' observed in LM; myelin sheaths, mitochondria, Nissl substance, Golgi bodies, synaptic vesicles, and endoplasmic reticulum could be excluded as the basis for neuronal argyrophilia. Unfortunately, the composition of these neurofibrils was obscure because of poor tissue preservation involved with proper impregnation, but they appeared to correspond to microtubules and neurofilaments. Neuronal structures containing a predominance of either organelle were impregnated with protargol. Nuclei and nucleoli of neuronal and nonneuronal cells were densely stained with silver as visualized with LM and TEM. Not every neuron was impregnated with protargol, but under conditions of improper fixation some of these neurons had an electron-dense cytoplasm which exhibited a definite affinity for silver. A discussion of protargol selectivity is also presented.

Animals↗

Correlation of peripheral receptive field area and rostrocaudal locus of neurons within the raccoon cuneate nucleus.

There is a significant positive correlation between peripheral receptive field (RF) area and neuron locus within the rostrocaudal extent of the raccoon cuneate nucleus for units having tactile RFs on the glabrous surfaces of the forepaw digits, larger RFs being associated with more rostrally located neurons, smaller ones with caudally situated neurons, but not for units having tactile RFs on the glabrous surfaces of the palm. For digits and palm, RF areas of neurons of the cuneate nucleus are approximately 40 and 100 times larger, respectively, than RF areas of primary afferent fibers of the cuneate fasciculus.

Animals↗