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Abstract: Basal forebrain cholinergic system: a functional analysis. Olton D, Markowska A, Voytko ML, Givens B, Gorman L, Wenk G. Department of Psychology, Johns Hopkins University, Baltimore, MD 21218. This chapter has been organized empirically, focusing on the types of approaches that have been taken to understand BFCS function. This approach reflects the state of our knowledge about the behavioral and psychological functions of the BFCS. Considerable information has been gathered in the very short time that the BFCS has been the object of intense investigation. The results from the neurotoxic lesions and from the HACU studies provide some points of consistency and some puzzling differences. Both approaches to the study of basal forebrain function suggest that the MSA is involved in tasks that require spatial working memory; MSA lesions impaired choice accuracy, and HACU in the HIP was increased after performance. The pattern of results in simpler tasks is more difficult to interpret. In a left-right reference memory discrimination in a T-maze, MSA lesions did not impair acquisition or performance, whereas HACU in the HIP was activated during performance. This pattern of results suggests that although the MSA is engaged during this type of task, its activity is not necessary for normal performance. These, and other comparisons indicate the need for a systematic analysis of task demand (Olton, 1989b). Parametric manipulations of different task demands in a systematic fashion can indicate the extent to which the BFCS is involved in the function associated with each parametric manipulation. Ultimately, of course, the organization of this material should focus on particular psychological functions, rather than the techniques and procedures used to gather the information. Achieving this goal is going to require careful attention to the design of behavioral experiments so that definitive conclusions can be made about the extent to which the BFCS is involved in a given psychological function. A systematic application of task analysis can achieve this goal (Olton, 1986, 1989a, 1989b). For example, BFCS lesions in rats impair choice accuracy in spatial working memory tasks, and performance in these tasks engages the HACU system, at least in the HIP. If the spatial functions of this task involve the BFCS, then a nonspatial version of the task should produce a different pattern of results. If the spatial nature of the task is unimportant for BFCS function, then a nonspatial version of the task should produce the same results. By systematically changing one characteristic of the task at a time, the contribution of each component can be assessed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID: 1776577 [PubMed - indexed for MEDLINE]
Abnormal development of the cholinergic basal forebrain has been implicated in numerous developmental disabilities such as Rett Syndrome and Down Syndrome. This review summarizes recent data using two rodent animal models that involve interrupting cholinergic basal forebrain projections on postnatal day 1 and postnatal day 7 when basal forebrain fibers are beginning to innervate their neocortical and hippocampal targets, respectively. In one model, electrolytic lesions in mice aimed at the basal forebrain on postnatal day 1 transiently reduce c...
Unilateral injections of kainic acid into the basal forebrain in a series of rats resulted in an increase in large amplitude slow waves, a correlated burst-suppression pattern of multi-unit activity, and a decrease in acetylcholinesterase staining in the neocortex ipsilateral to the kainic acid injection. Subsequently, a cell suspension, prepared from rat embryonic basal forebrain tissue, was injected adjacent to the recording electrodes ipsilateral to the kainic acid injection. This produced a gradual recovery of low voltage fast activity (LVF...
The distribution of the reticular neuronal type in the human brain and its involvement in both degeneration and dendritic reorganisation under the conditions of ageing, Korsakoff's disease (KD), Alzheimer's disease (AD), and Parkinson's disease (PD) was comparatively investigated after Golgi impregnation. Reticular neurones are distributed throughout different areas along the brain axis. The cholinergic basal forebrain nuclei, i.e., the basal nucleus of Meynert, the nucleus of the diagonal band, and the medial septal nucleus form the most rostr...
In this study the location of dopamine (DA) neuron perikarya in the rostral mesencephalon of the rat was determined using the glyoxylic acid fluorescence histochemical technique. Subsequently the topography of the projection of these mesencephalic neurons on the basal forebrain and striatum was analyzed using the anterograde transport-autoradiographic tracing method and the retrograde transport-horseradish peroxidase (HRP) technique. The results of these anatomical studies were correlated with the biochemical and histochemical studies presented...
The memory disturbance of senile dementia of Alzheimer type has been thought to associate with marked degeneration and loss of cholinergic neurons of the basal forebrain (nucleus basalis of Meynert, NBM). Electrical or chemical destruction of the NBM causes memory deficits in rats. After unilateral lesioning of the NBM in adult rats with excitotoxic amino acid, kainic acid, basal forebrain cells of fetal rats were transplanted through a microsyringe needle, the tip of which was transcortically inserted to the subarachnoid space. Eight weeks aft...
Six Rhesus monkeys between 24 and 29 years of age received unilateral transections of the fornix. Three monkeys then received intraventricular transplants of polymer-encapsulated baby hamster kidney (BHK) fibroblasts that had been genetically modified to secrete human nerve growth factor (hNGF). The remaining three monkeys received identical grafts except the cells were not modified to secrete hNGF. Monkeys receiving the fornix transection and control grafts displayed extensive reductions in the number of choline acetyltransferase- (57-75%) and...
Following injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) or the fluorescent tracer fluoro-gold into the magnocellular preoptic area and the horizontal limb of the diagonal band, retrogradely labelled neurons were found in the homotopic region of the contralateral basal forebrain. Labelled fibers apparently arising from these neurons travelled in the stria medullaris and the habenular commissure to terminate in the contralateral basal forebrain. Although the neurons retrogradely labelled with fluoro-gold in the c...
One group of six male control rats [21 months old] and one group of six male rats of the same age, singularly stored in a cage, and treated with acetyl-l-carnitine-HCl (ALCAR: 60 mg/kg/day/p.o.) for six months were tested in the spatial learning/memory Morris maze-water task and for atrophy and cell loss in seven myelo- and cytostructurally defined basal forebrain (BF) cholinergic regions [Gritti et al., 1993 J Comp Neurol 329: 438-457]. Coronal sections 25 mum thick were cut through the BF regions and processed every 200 mum for choline acetyl...
In the present study, the dendritic organisation of neurones in the normal human basal forebrain was analysed as a prerequisite for the evaluation of pathological changes occurring in Alzheimer's disease and related conditions (see other Arendt et al. papers in this issue). Neurones in the basal nucleus of Meynert (NbM), the nucleus of the vertical limb of the diagonal band, and the medial septal nucleus were examined after Golgi impregnation. Cells were classified according to the dendritic branching pattern and soma shape as either reticular ...
The process of degeneration and dendritic reorganization of cholinergic neurons was investigated in the rat basal forebrain under the conditions of chronic neurotoxic injury induced by long-term consumption of ethanol. After 28 weeks of ethanol treatment (20% v/v), both the number of choline acetyltransferase-immunoreactive basal forebrain neurons and levels of biochemical measures of cholinergic neurons, such as the activity of choline acetyltransferase and the synthesis and content of acetylcholine, were decreased by about 60-80%. The number ...
Oral administration of ethanol (20% v/v) to male Sprague-Dawley rats for different periods of time up to 28 weeks resulted in profound reductions of acetylcholine content, in vitro synthesis and release of acetylcholine, choline uptake, activities of choline acetyltransferase, acetylcholinesterase and pyruvate decarboxylase, content of noradrenaline, serotonin and, to a lesser extent, dopamine throughout the brain. Changes were fully and partially reversible by a 4 weeks' ethanol-free period following a treatment of 8 and 18 weeks, respectively...
Current autoradiographic and electrophysiological data suggest that fibers coursing from the diagonal band/medial septum and lateral preoptic area through the medial forebrain bundle (MFB) to the midbrain may carry the reward signals generated by lateral hypothalamic stimulation. To test this hypothesis, 40 rats were given a unilateral lateral hypothalamic stimulating electrode and an ipsilateral guide cannula for knife cut transection. In baseline self-stimulation testing, both the animal's capacity to respond for the stimulation and the rewar...