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Biomedical subjects

L K Gorman

Publications and source records attributed to L K Gorman.

14 recordsLinked to original sources
PubMed1999

Presynaptic markers of cholinergic function in the rat brain: relationship with age and cognitive status.

The nature of age-related changes in cholinergic function and their relationship to age-related behavioral decline were examined in the present study. Male Fischer-344 rats of four ages (four, 11, 17 and 23 months) were tested in a battery of cognitive tasks. Discrete microdissections of brain areas involved in cognitive function were performed, and activity of choline acetyltransferase and levels of hemicholinium-3 binding were determined to assess the integrity of cholinergic innervation. Age-related changes in cholinergic markers occurred predominantly in the medial septal area and its target areas (hippocampus and cingulate cortex), and were also present in the posterior caudate. However, most of the age-related changes in cholinergic markers were already present at ages at which behavioral impairment was not yet maximal. There were some consistent correlations between behavioral and neurochemical measures, independent of age, but these accounted for relatively small proportions of variance in behavioral performance. For most of these correlations, lower levels of presynaptic cholinergic markers were related to better behavioral performance. In brain areas in which correlations changed with age, lower levels of presynaptic cholinergic markers were associated with better performance in young rats, whereas higher levels were associated with better performance in aged rats. Recent lesion studies using a toxin selective for basal forebrain cholinergic neurons have suggested that these neurons do not play as central a role in learning and memory in young and aged animals as was previously thought. When considered in this context, the present results suggest that preserved cholinergic function in old age might act indirectly to sustain cognitive ability. Changes in cholinergic function may represent one of a number of age-related neurobiological events that underlie behavioral impairments, or may be a permissive factor for other age-related processes that are more directly responsible for cognitive impairments.

Acetylcholine↗
PubMed1996

Intact spatial learning following lesions of basal forebrain cholinergic neurons.

The role of the basal forebrain cholinergic system in learning and memory has held considerable interest since the discovery of cholinergic neurodegeneration in the basal forebrain in Alzheimer's disease. Contrary to expectation, selective removal of basal forebrain cholinergic neurons projecting to either hippocampus or neocortex fails to impair learning in a spatial task widely used to study hippocampal/cortical function. If cholinergic neurons contribute to learning and memory by integrated regulation of hippocampal and cortical processing, combined removal of hippocampal and cortical cholinergic projections might be necessary to produce impairment. However, this combined lesion failed to impair spatial learning. These data argue against the view that basal forebrain cholinergic deficiency plays a prominent role in disorders of learning and memory.

Acetylcholine↗
PubMed1996

Oxotremorine infusions into the medial septal area of middle-aged rats affect spatial reference memory and ChAT activity.

Age-related spatial memory deficits are correlated with septohippocampal cholinergic system degeneration. The present study examined the effect of intraseptal infusions of the cholinergic agonist, oxotremorine, on spatial reference memory in middle-aged rats using place discrimination in the water maze, and on cholinergic activity using choline acetyltransferase (ChAT) activity. Oxotremorine mildly improved the rate of place discrimination acquisition of middle-aged rats during initial sessions only, but did not affect asymptotic levels of performance achieved. Of the brain regions assayed, ChAT activity increased with age in the temporal cortex and dorsal CA2/3 region of the hippocampus. Oxotremorine significantly decreased ChAT activity in the dorsal hippocampus. In contrast to our previous results in aged rats indicating a more robust effect of oxotremorine on spatial working memory, the present results suggest a modest effect of intraseptal oxotremorine on the acquisition of a spatial reference memory task.

Aging↗
PubMed1996

Effects of traumatic brain injury on the cholinergic system in the rat.

Rats subjected to a mild to moderate fluid percussion injury exhibit memory deficits that are similar to rats that have received lesions of the septohippocampal system. Because the cholinergic system plays a major role in septohippocampal function, we studied the kinetics of the synthetic enzyme for acetylcholine, choline acetyltransferase (ChAT), at 1 h, 24 h, or 5 days after a fluid percussion injury. Decreases in ChAT activity were found in the dorsal hippocampus (25%), frontal (32%), and temporal (23%) cortices 1 h after injury. In the parietal cortex, a greater than 50% increase in ChAT activity was observed at all time intervals assessed. At 5 days after TBI, there was an 18% increase in ChAT activity in the medial septal area. These data provide evidence that a mild to moderate fluid percussion injury produces changes in the cholinergic system in brain areas related to memory.

Analysis of Variance↗
PubMed1995

Nitric oxide synthase inhibition does not impair visual or spatial discrimination learning.

Nitric oxide (NO) is a candidate retrograde messenger involved in synaptic plasticity, and is linked to the cholinergic system in the brain. We examined the role of NO in the acquisition of visual and spatial discriminations by daily administration of either saline or 1-nitroarginine methyl ester (L-NAME), an NO synthase inhibitor. Brains were assayed for NO synthase activity and two presynaptic cholinergic markers: hemicholinium-3 (HC-3) binding, which determines the number of sodium-dependent high-affinity choline uptake sites, and activity of choline acetyltransferase (ChAT), which is the synthetic enzyme for acetylcholine. In both behavioral tasks, the acquisition rate was not different between groups. L-NAME reduced NO synthase activity by 85% in all brain areas assayed and HC-3 binding by 38% in hippocampus and 48% in posterior cortex. ChAT activity was not different between groups in any region assayed. These data suggest that NO does not play a role in visual or spatial discrimination learning. However, NO synthase inhibition may play a role in the regulation of cholinergic activity.

Animals↗
PubMed1995

Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats.

Male Long-Evans rats were given injections of either 192 IgG-saporin, an apparently selective toxin for basal forebrain cholinergic neurons (LES), or vehicle (CON) into either the medial septum and vertical limb of the diagonal band (MS/VDB) or bilaterally into the nucleus basalis magnocellularis and substantia innominata (nBM/SI). Place discrimination in the Morris water maze assessed spatial learning, and a trial-unique matching-to-place task in the water maze assessed memory for place information over varying delays. MS/VDB-LES and nBM/SI-LES rats were not impaired relative to CON rats in acquisition of the place discrimination, but were mildly impaired relative to CON rats in performance of the memory task even at the shortest delay, suggesting a nonmnemonic deficit. These results contrast with effects of less selective lesions, which have been taken to support a role for basal forebrain cholinergic neurons in learning and memory.

Acetylcholinesterase↗
PubMed1994

Acetylcholine release in the hippocampus: effects of cholinergic and GABAergic compounds in the medial septal area.

The medial septal area (MSA) contains cholinergic and GABAergic neurons that send projections to the hippocampus. These neurons have both cholinergic and GABAergic receptors. This study was designed to determine the effects of intraseptal infusions of cholinergic and GABAergic drugs, which alter mnemonic processes, on hippocampal acetylcholine (ACh) release. Hippocampal ACh release was assessed using in vivo microdialysis and HPLC-EC. Oxotremorine and scopolamine produced a dose-dependent decrease in hippocampal ACh release. Muscimol decreased hippocampal ACh release at both high and low doses, although not in a dose-dependent manner. The effects of scopolamine and muscimol are consistent with a role of ACh in mnemonic processing.

Acetylcholine↗
PubMed1994

Basal forebrain lesions in monkeys disrupt attention but not learning and memory.

Cognitive impairments in humans and animals have been linked to dysfunction of neurons in the basal forebrain cholinergic system (BFCS). Degeneration of these cells may be, in part, responsible for some of the cognitive deficits observed in Alzheimer's disease (AD). Although memory deficits are associated with lesions of the BFCS in rats, impairments in memory have been more subtle following similar lesions in monkeys. To evaluate the effects of BFCS lesions on cognitive processes in monkeys, we have systematically investigated the behavioral effects of ibotenic acid injections in the medial septum, nucleus of the diagonal band of Broca, and nucleus basalis of Meynert in cynomolgus monkeys, using a large series of cognitive tasks that examined different mnemonic and attentional abilities. These lesions did not impair accuracy in delayed nonmatching-to-sample, delayed response, simple or concurrent visual discriminations, spatial discriminations, or discrimination reversals. However, these lesions disrupted attentional focusing. Similar impairments in attention have been noted in patients with AD. BFCS lesions increased sensitivity to injections of the cholinergic antagonist scopolamine in a delayed nonmatching-to-sample task, indicating that the central cholinergic system was compromised in these monkeys. In concert, the results of this study suggest that the primate basal forebrain may be more involved in attentional than mnemonic processes, and that degeneration of neurons in the BFCS in cases of AD may contribute to the attention deficits observed in these individuals.

Animals↗
PubMed1993

Traumatic brain injury produces impairments in long-term and recent memory.

Traumatic brain injury (TBI) in humans typically produces neurological suppression and a longer lasting impairment of memory clinically defined as post-traumatic amnesia. An animal model that reliably reproduces the physiological changes associated with TBI was used to assess the memory deficits following brain injury. Prior to TBI, rats were trained to perform one of four tasks that assessed either motor performance, long-term or recent memory. Rats were randomly assigned to one of three groups (anesthesia only, sham operation or fluid percussion). Following fluid percussion, used to produce TBI, rats were tested for 6 test sessions. The first session occurred 1-2 min after the experimental manipulation. The next 5 sessions followed the training schedule maintained prior to experimental manipulation. Differences in long-term memory occurred only in the first post-operative test session. Differences in recent memory performance were found across all 6 test sessions. The memory deficits were clearly dissociated from motor deficits. The similar memory deficits observed following human head injury and the experimentally produced TBI injury demonstrate that fluid percussion is a useful approach to examine underlying neurobiological mechanisms involved in head injury and possible clinical interventions.

Animals↗
PubMed1984

Age and the dexamethasone suppression test in depression.

The authors examined the effects of age on plasma cortisol concentrations of 81 depressed men after dexamethasone administration. Dexamethasone nonsuppression was significantly more frequent in patients older than age 55 than those younger. Similarly, older patients had significantly higher postdexamethasone cortisol concentrations than younger patients at all time points sampled. These differences could not be attributed to severity or to the prevalence of psychosis in older and younger depressed patients.

Adolescent↗
PubMed1984

Advantages of a simple contact switch for human locomotion.

A simple, inexpensive foot switch was fabricated to record the duration of surface contact for part or all of the foot during human locomotion. The device incorporated electrically conductive metallic foil in a thin foam insole. Advantages over a more conventional thick-soled sandal were documented for the same subjects by examining kinematic values (read from movie film) and electrical signal data (produced by the switch). A person's characteristic manner of placing and lifting the foot while wearing conventional shoes could in some instances distort readings of stance duration by many tens of msec, but the new switch assembly eliminated ambiguities of measurement and interpretation.

Biomedical Engineering↗
PubMedDate not supplied

Drug treatment of social phobia.

Social phobia is a potentially serious anxiety disorder that has attracted research interest in the U.S.A. very recently. Patients with social phobia suffer severe anxiety only in the context of social situations. Men are more likely to be afflicted than women. Alcohol and drug abuse are frequent complications. Two classes of medication are promising in treating this condition--beta-adrenergic receptor blockers and monoamine oxidase inhibitors. Data supporting the use of these drugs are reviewed and recommendations for pharmacologic management of social phobics are outlined.

Adrenergic beta-Antagonists↗