Biomedical subjects

P R Rapp

Publications and source records attributed to P R Rapp.

12 recordsLinked to original sources

PubMed1992

Individual differences in the cognitive and neurobiological consequences of normal aging.

Defining the neural basis of age-related cognitive dysfunction is a major goal of current research on aging. Compelling evidence from laboratory animals and humans indicates that aging does not inevitably lead to cognitive decline. Conducting neurobiological investigations in subjects that have previously undergone behavioral characterization has therefore emerged as a promising strategy for identifying those alterations in brain structure and function that are specifically associated with age-related cognitive impairment.

Aging↗

PubMed1992

Cholinergic cell loss and hypertrophy in the medial septal nucleus of the behaviorally characterized aged rhesus monkey.

Quantitative studies were conducted to determine the number and size of cholinergic neurons in the medial septal nucleus of four aged (23-25 years old) and four young (10-12 years old) rhesus monkeys. All of the animals had been tested on an extensive battery of learning and memory tasks prior to these experiments. Two of the aged monkeys displayed a pattern of recognition memory deficits that resembled the effects of medial temporal lobe damage. The postmortem anatomical data were analyzed in relation to both the age and behavioral status of the animals. Across all rostrocaudal levels of the medial septal nucleus, there was a 19.3% decrease in the number of cholinergic neurons in the aged monkeys. The loss was regionally selective, however, and ranged from a low of 6.2% rostrally to 40.9% caudally. The degree of cell loss was similar in both memory-impaired and memory-unimpaired aged animals. Morphological analysis also revealed that the mean cross-sectional area of cholinergic neurons was significantly larger in the aged animals. At caudal levels, the increase in average cell size was at least partly due to a disproportionate loss of small to medium size neurons. At rostral levels of the medial septal nucleus, however, where there was minimal cell loss, a clear hypertrophy of cholinergic neurons was evident. Interestingly, the cell hypertrophy observed at these rostral levels was present only in brains from the behaviorally impaired aged monkeys. These findings represent the first morphological demonstration of alterations in cholinergic neurons in the aged nonhuman primate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1990

Visual discrimination and reversal learning in the aged monkey (Macaca mulatta).

Visual discrimination and reversal learning were assessed in young adult (10-12 years old, n = 4) and aged (23-27 years old, n = 5) female rhesus monkeys. Performance was comparable across age groups in many tasks, suggesting that the acquisition of stimulus-reward associations remains largely intact in the aged monkey. Most older subjects, however, required more training than any young animal to learn an initial pattern discrimination. In combination with previous findings from the same groups of monkeys, these data suggest that deficits in attending to the relevant stimulus features in novel testing procedures may contribute to poor performance in aged subjects across a variety of learning and memory tasks. In addition, preliminary findings from a discrimination probe procedure raise the possibility that aged subjects may adopt alternate testing strategies that compensate for some aspects of age-dependent cognitive dysfunction.

Aging↗

PubMed1989

Evidence for task-dependent memory dysfunction in the aged monkey.

Experimentally naive adult (9-11 years old) and aged (approximately 22-26 years old) female rhesus monkeys were evaluated on 3 neuropsychological tests of memory function. Aged monkeys were impaired in a delayed response test of visuospatial memory when the retention interval of the task was increased from 0 to 10 sec. These animals performed as well as younger subjects, however, at very short delays (0 and 1 sec), when the memory demands of the task were minimal. The same subjects were then trained in a delayed nonmatching to sample (DNMS) test of visual object recognition memory. Although they required significantly more training than the younger subjects to learn the nonmatching principle of the task, aged animals were only minimally impaired when recognition memory was tested at retention intervals ranging from 10 sec to 22 hr. In contrast to their relatively intact performance on the object recognition task, aged monkeys were dramatically impaired in a second version of DNMS that required subjects to remember the temporal order in which objects were presented. These findings support the view that certain memory functions are differentially susceptible to age-dependent deterioration. Since neuropsychological studies in young subjects demonstrate that different brain regions make relatively specific contributions to learning and memory, the task-dependent deficits observed in the aged monkey are important for determining which neural structures mediate age-dependent cognitive dysfunction. According to this perspective, aged monkeys were impaired on tasks known to be sensitive to prefrontal cortical damage, but the same animals performed well on a DNMS procedure that subjects with medial temporal lobe damage fail. These results suggest that prefrontal cortical dysfunction may mediate prominent aspects of age-dependent cognitive impairment in the monkey.

Aging↗

PubMed1988

The time of origin of somatostatin-immunoreactive neurons in the rat hippocampal formation.

Experiments utilizing a combination of [3H]thymidine autoradiography and immunohistochemistry were conducted to determine the time of origin of somatostatin-immunoreactive (SSIR) neurons in the hippocampal formation of the rat. A quantitative and topographic description of neurogenesis in this peptide-containing neuronal system was generated using a computer-aided system to plot the position of labeled cells. Dissected and 'flattened' hippocampal preparations were used to facilitate the analysis of spatial gradients of SSIR cell development. The results indicate that most SSIR hippocampal cells are generated during a short embryonic period which extends from the 12th through the 15th day of gestation (E12-E15). Within this period of development, the distribution of SSIR cells follows a spatial gradient along the transverse or subiculo-dentate axis of the hippocampus. The earliest formed SSIR neurons, generated on E12 and E13, are preferentially distributed to the subiculum, those generated on E14 are most commonly observed throughout the CA1-CA3 fields of the hippocampus and SSIR neurons which become postmitotic on E15 are more heavily represented in the hilar region of the dentate gyrus than cells born at other stages of development. There was no clear-cut neurogenic gradient along the septotemporal axis of the hippocampus. These results indicate that somatostatin cells in the rat hippocampal formation are generated during the same prenatal period when glutamic acid decarboxylase (GAD)-positive neurons become postmitotic. These studies also suggest that quantitative developmental analyses of chemically specific cell types can reveal prominent features of cortical ontogeny that are not readily apparent in standard [3H]thymidine preparations.

Aging↗

PubMed1987

Alterations in [3H]desmethylimipramine binding in the aged rat brain: an in vitro autoradiographic demonstration.

Using in vitro autoradiographic receptor binding, the present report provides a descriptive analysis of [3H]desmethylimipramine ([3H]DMI) binding in the aged rat brain. Small circular patches of intense [3H]DMI binding were present within the caudate nucleus in every aged brain examined. Occasionally, similar patches of label were present in restricted cortical regions of aged brains. Comparable patches of [3H]DMI binding were never observed in young brains used in these investigations. Additional evidence suggests that these age-dependent changes in [3H]DMI binding are anatomically restricted to the loci indicated above.

Aging↗

PubMed1987

An evaluation of spatial information processing in aged rats.

The spatial learning abilities of young, middle-age, and senescent rats were investigated in two experiments using several versions of the Morris water maze task. In Experiment 1, Long-Evans hooded rats were trained to find a submerged escape platform hidden within the water maze. During this phase of testing, aged rats exhibited acquisition deficits compared with either young or middle-age subjects. With continued training, however, all age groups eventually achieved comparable asymptotic levels of performance. Subsequent testing in Experiment 1 revealed that following original training, aged rats were not impaired in learning a novel escape location or in their ability to locate a visible, cued escape platform. In an attempt to identify the basis of the age-related impairments observed in Experiment 1, naive young and aged rats in Experiment 2 were initially tested for their ability to locate a cued escape platform in the water maze. During this phase of testing, the escape latencies of both young and aged rats rapidly decreased to equivalent asymptotic levels. Subsequent analyses revealed that following cue training, young subjects exhibit a significant spatial bias for the region of the testing apparatus where the platform was positioned during training. In contrast, aged rats showed no spatial bias. Training was continued in Experiment 2 using a novel submerged platform location for each subject. During these place training trials, the escape latencies of senescent rats were longer than those of young subjects. These impairments were also accompanied by a lack of spatial bias among aged rats relative to young control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1985

Opiate antagonist facilitation of time-dependent memory processes: dependence upon intact norepinephrine function.

Post-training administration of opiate antagonists improves retention of recent learning in laboratory animals tested on a variety of tasks. We examined the possibility that this effect of opiate antagonist treatment might be due to release of brain norepinephrine (NE) function from opioid peptide inhibition. The behavioral testing procedure in the experiments consisted of one-trial passive avoidance conditioning. Rats received post-training treatments immediately after the training trial and retention was tested 24 h later. Lesions of the dorsal noradrenergic bundle (DNB) that were induced by 6-hydroxydopamine (6-OHDA) were found to prevent the memory enhancing effect of post-training naloxone administration. The memory enhancing effect of naloxone was restored when NE neurons were protected from 6-OHDA by pretreatment with a NE uptake inhibitor. Earlier research indicated that the amygdala complex is one brain site that is sensitive to the effects of opiate manipulations on memory processes. In this study, lesions of the DNB were also found to prevent the memory enhancing effect of intracranial opiate antagonist administration into the amygdala complex.

Amygdala↗

PubMed1982

Amygdaloid and basal forebrain direct connections with the nucleus of the solitary tract and the dorsal motor nucleus.

Although the amygdala complex has long been known to exert a profound influence on cardiovascular activity, the neuronal and connectional substrate mediating these influences remains unclear. This paper describes a direct amygdaloid projection to medullary sensory and motor structures involved in cardiovascular regulation, the nucleus of the solitary tract (NTS) and the dorsal motor nucleus (DVN), by the use of autoradiographic anterograde transport and retrograde horseradish peroxidase (HRP) techniques in rabbits. Since all of these structures are highly heterogeneous structurally and functionally, details of the specific areas of the neuronal origin and efferent distribution of the projection were examined in relation to these features and with reference to a cytoarchitecture description of the relevant forebrain regions in the rabbit. Amygdaloid projections to the NTS and DVN, as determined from HRP experiments, arise from an extensive population of neurons concentrated exclusively within the ipsilateral central nucleus and confined to and distributed throughout a large medial subdivision of this nucleus. Projection neurons, however, also distribute without apparent interruption beyond the amygdala dorsomedially into the sublenticular substantia innominata and the lateral part of the bed nucleus of the stria terminalis and thus delineate a single entity of possible anatomical unity across all three structures, extending rostrocaudally within the basal forebrain as a diagonal band. Descending central nucleus connections, based upon autoradiographic experiments, project heavily and extensively to both the NTS and the DVN. Within both nuclei, the projections have a highly specific distribution pattern, appearing to correspond largely to structural subdivisions, including the dorsomedial, medial, ventrolateral, ventral, and commissural NTS, and to cell group "a," a caudally located dorsomedial region, and peripheral regions of the DVN, some of which appear to be involved in cardiovascular regulation. The existence of such an extensive projection system connecting these specific regions is significant evidence in support to its potential for participation in the amygdaloid expression of cardiovascular influences and has important implications for the cellular analysis of the functional role of these influences.

Afferent Pathways↗

PubMed1980

beta-Adrenergic manipulation in amygdala central n. alters rabbit heart rate conditioning.

The present study was conducted to assess the effects of beta-adrenergic manipulation within the central nucleus of the amygdala on Pavlovian heart rate conditioning in the rabbit. Administration of the beta-adrenergic antagonist dl-propranolol into the central nucleus impaired the acquisition of conditioned heart rate responding compared to a vehicle injected control group. No significant effects of dl-propranolol on either baseline heart rate or on the heart rate orienting response were observed. The effect of dl-propranolol on conditioning exhibited stereospecificity, and animals receiving combined intracerebral injections of dl-propranolol and the beta-adrenergic agonist 1-isoproterenol did not exhibit comparable conditioning impairments. In addition, dl-propranolol administration dorsal to the central nucleus or into amygdala sites anterior or posterior to the central nucleus was less effective. These results support the interpretation that beta-adrenergic activity within the central nucleus region of the amygdala complex contributes to the acquisition of classically conditioned heart rate responding.

Amygdala↗

PubMedDate not supplied

Recognition memory deficits in a subpopulation of aged monkeys resemble the effects of medial temporal lobe damage.

The present study examined individual differences in recognition memory function in a group of Old World monkeys (Macaca mulatta). Four young (9-11 years) and 10 aged (22-33 years) monkeys were tested in the same delayed-nonmatching-to-sample (DNMS) recognition memory procedure that has been widely used to study the effects of experimental hippocampal lesions in young subjects. Animals were first trained to a 90% correct learning criterion in the DNMS task using a 10-second delay between the sample and recognition phase of each trial. The memory demands of the task were then increased by gradually extending the retention interval from 15 seconds to 10 minutes. Three of the aged monkeys performed as accurately as young subjects at all delays. The remaining aged monkeys performed well at the shortest delays (15 and 30 seconds), but progressively greater impairments emerged across delays of 60 seconds, 2 minutes, and 10 minutes. These results suggest that recognition memory is only compromised in a subpopulation of aged monkeys. Moreover, aged monkeys that are impaired in the DNMS task exhibit the same delay-dependent pattern of deficits that is the hallmark of memory dysfunction resulting from medial temporal lobe damage.

Aging↗

PubMedDate not supplied

Toward a nonhuman primate model of age-dependent cognitive dysfunction.

Neuropsychological studies of memory function in young subjects have provided a valuable strategy for developing a nonhuman primate model of age-dependent cognitive dysfunction. This approach suggests specific directions for future research and underscores the importance of appropriate behavioral analyses in efforts to identify the neural basis of age-related cognitive decline.

Aging↗