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Biomedical subjects

P R Solomon

Publications and source records attributed to P R Solomon.

At least 19 recordsLinked to original sources
PubMed1991

Hippocampus, context, and conditioning.

Rabbits (Oryctolagus cuniculus) with lesions to either the hippocampus or overlying neocortex and unoperated controls underwent acquisition of the classically conditioned nictitating membrane response to a tone conditioned stimulus and an air puff unconditioned stimulus until they reached a criterion of 8 conditioned responses in any block of 10 trials. They were then returned to their cages. On the next day, they were either placed in the same context in which they underwent initial conditioning or switched to a new context that distinctly differed along olfactory, visual, and tactile dimensions. In relation to unswitched controls, rabbits with lesions to the neocortex and unoperated controls showed a disruption of conditioning when contexts were switched. In contrast, rabbits with lesions to the hippocampus performed at the same levels as unswitched controls. The results are discussed in terms of the possible role of hippocampus in coding context in classical conditioning.

Animals↗
PubMed1991

Attenuation of age-related conditioning deficits in humans by extension of the interstimulus interval.

Young (17-22 years) and older (61-86 years) persons underwent classical conditioning of the eye-blink response to a tone conditioned stimulus (CS) and an airpuff unconditioned stimulus (UCS) at 1 of 3 interstimulus intervals (ISIs; 400, 650, and 900 ms). As in a previous study, older subjects conditioned more slowly and emitted fewer conditioned responses at the optimal 400-ms ISI. At longer ISIs, however, this age-related disruption of classical conditioning was attenuated. These differences in conditioning were not due to nonassociative factors, such as sensitivity to the tone CS or airpuff UCS or to differences in spontaneous blink rate, nor were they due to differences in general cognitive abilities. The results are discussed in terms of the role of temporal relationships between stimuli in conditioning across the life span.

Adolescent↗
PubMed1989

Neurochemical characteristics of aluminum-induced neurofibrillary degeneration in rabbits.

Aluminum-induced neurofibrillary degeneration in rabbits is known to affect particular populations of neurons. The neurotransmitter alterations which accompany aluminum neurofibrillary degeneration were examined in order to assess how closely they mimic those of Alzheimer's disease. There was a significant reduction in choline acetyltransferase activity in entorhinal cortex and hippocampus as well as significant reductions in cortical concentrations of serotonin and norepinephrine in the aluminum-treated rabbits. Significant reductions in glutamate, aspartate and taurine were found in frontoparietal and posterior parietal cortex. Concentrations of GABA were unchanged in cerebral cortex. Both substance P and cholecystokinin immunoreactivity were significantly reduced in entorhinal cortex but there were no significant changes in somatostatin, neuropeptide Y and vasoactive intestinal polypeptide. The five neuropeptides were unaffected in striatum, thalamus, cerebellum and brainstem. Neurochemical changes were found in the regions with the most neurofibrillary degeneration while regions with little or no neurofibrillary degeneration were unaffected. The reductions in choline acetyltransferase activity, serotinin and noradrenaline suggest that some neuronal populations preferentially affected in Alzheimer's disease are also affected by aluminum-induced neurofibrillary degeneration; however, the cortical somatostatin deficit which is a feature of Alzheimer's disease is not replicated in the aluminum model.

Aluminum↗
PubMed1989

Disrupted eyelid conditioning in a patient with damage to cerebellar afferents.

A 54-year-old woman with damage to cerebellar circuitry resulting from a cerebrovascular accident underwent classical conditioning of the eye-blink response to a tone conditioned stimulus and an air-puff unconditioned stimulus. In contrast to 5 age-matched controls who readily acquired the conditioned response (CR), emitting a mean of 56.7 CRs over 70 trials, the patient emitted only 6 CRs in 100 trials and never emitted 2 consecutive CRs. There were no differences in spontaneous blink rate, sensitivity to the air puff, or sensitivity to the tone between the experimental subject and the control subjects. That conditioning of the eye-blink response is disrupted in a human with damage to cerebellar circuitry is consistent with an accumulating body of literature indicating that the cerebellum is the essential site of plasticity for classically conditioned somatic responses.

Afferent Pathways↗
PubMed1989

Acquisition of the classically conditioned eyeblink response in humans over the life span.

Human subjects ranging in age from 18 to 85 years underwent classical conditioning of the eyeblink response to a tone conditioned stimulus (CS) and an air-puff unconditioned stimulus (UCS). There was a decline in percentage of conditioned responses with age. This decline was most noticeable in subjects over age 50. These conditioning deficits were not due to age-related changes in sensitivity to the tone CS or the air-puff UCS, nor could the conditioning deficits be attributed to an age-related decline in general cognitive abilities or to changes in spontaneous blink rates. The results are discussed in terms of using the classically conditioned eyeblink in humans in conjunction with the classically conditioned nictitating membrane response in rabbits as a model system for studying the neurobiology of age-related conditioning deficits.

Adolescent↗
PubMed1988

Aluminum-induced neurofibrillary degeneration disrupts acquisition of the rabbit's classically conditioned nictitating membrane response.

Rabbits received intraventricular injections of aluminum chloride, hydrochloric acid, or served as unoperated controls. On the 6th day postsurgery, they underwent 4 days (100 trials per day) of classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus and an air-puff unconditioned stimulus. Unoperated and hydrochloric acid control animals readily acquired the conditioned response. Aluminum intoxicated rabbits, in contrast, did not acquire the conditioned response over the 4 days of testing. This disruption of conditioning in aluminum-treated rabbits could not be attributed to deficits in sensory or motor processes or to illness. Neuropathological analysis revealed widespread neurofibrillary tangle formation in aluminum-treated animals. Furthermore, the degree of neurofibrillary degeneration was significantly negatively correlated with the degree of conditioning. The results are considered in the context of using the rabbit NMR preparation as a model system for studying age-related conditioning disorders.

Aluminum↗
PubMed1988

A model systems approach to age-related memory disorders.

Memory deficits are common to virtually all forms of cognitive dysfunction and are central to disorders associated with aging. Animal models provide the opportunity to understand normal and pathologic memory in great detail. The model systems approach to the neurobiology of memory involves studying a well characterized learned response in a relatively simple and well controlled preparation. The best characterized mammalian model system is classical conditioning of the rabbit's eyeblink response. Using this preparation, significant progress has been made toward understanding the neurobiological systems and mechanisms involved in elaboration of the conditioned response. Using a well characterized model system such as classical eyeblink conditioning, it should be possible to both characterize the changes in learning and memory that accompany aging and to investigate their neural substrate. Our strategy for using the conditioned eyeblink preparation for studying age-related memory deficits is fourfold and includes investigating conditioning deficits in: (1) humans across the life-span, (2) rabbits across the life-span, (3) Alzheimer's disease patients, and (4) rabbits with aluminum-induced neurofibrillary degeneration. In this paper, we present exemplary data from each of these lines of research. If similar deficits occur in each of these groups, it may be possible to begin to form hypotheses about the neurobiology of age-related memory disorders.

Aging↗
PubMed1988

Neuropathologic, neurochemical and immunocytochemical characteristics of aluminum-induced neurofilamentous degeneration.

Inoculation of aluminum salts or metallic aluminum into the central nervous system of rabbits produces an encephalomyelopathy accompanied by widespread neurofibrillary degeneration (NFD) affecting restricted neuronal populations. Some investigators have suggested that this preparation may serve as an animal model for human neurodegenerative disorders, such as Alzheimer's disease (AD), in which neurofibrillary tangle (NFT) formation is a prominent histopathologic finding. However, neurochemical, immunocytochemical and behavioral features of the model are largely unknown and its neuropathology only partially described. We have undertaken a series of experiments designed to further characterize these aspects of the model. We have used an intraventricular route of injection of aluminum chloride and found that the distribution of NFD in rabbit brain is similar to the distribution of NFT formation in AD. Immunocytochemical probes demonstrate that phosphorylated neurofilaments accumulate in neuronal perikarya containing NFD, and double labelling techniques suggest that NFD affects primarily projection type neurons. The neurochemical profile of aluminum intoxicated rabbits shows both similarities and discrepancies to that of AD. Finally, as reported in a companion article in this issue of Neurotoxicology (Solomon and Pendlebury, 1988), aluminum-exposed rabbits develop learning and memory deficits which are strongly correlated with the degree of whole brain NFD but not with motor, sensory or motivational factors. We conclude that aluminum-induced NFD may have relevance for understanding NFT formation in AD and other neurodegenerative disorders in which abnormalities of the neuronal cytoskeletal architecture are present.

Aluminum↗
PubMed1988

Disrupted retention of the classically conditioned nictitating membrane response in rabbits with aluminum-induced neurofibrillary degeneration.

Rabbits underwent classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus and an air puff unconditioned stimulus until they emitted 90 percent or greater conditioned responses (CRs) for two consecutive days. They then received intraventricular injection of aluminum chloride, hydrochloric acid or saline. Ten days post injection they were tested for retention of the conditioned response. Animals injected with saline or hydrochloric acid emitted an average of greater than 90 percent CRs. Aluminum injected rabbits, in contrast, emitted an average of only about 40 percent CRs. This disruption of retention of conditioning in aluminum treated rabbits could not be attributed to deficits in sensory or motor processes or to illness. Neuropathological analysis revealed widespread neurofibrillary tangle formation in the aluminum treated animals. Furthermore, the degree of neurofibrillary degeneration was significantly negatively correlated with retention of the CR. The results are considered in the context of using the rabbit NMR preparation as a model system for studying age-related conditioning disorders.

Aluminum↗
PubMed1987

Lesions of the middle cerebellar peduncle disrupt acquisition and retention of the rabbit's classically conditioned nictitating membrane response.

Rabbits were classically conditioned to emit a nictitating membrane response (NMR) to either a light or tone conditioned stimulus (CS) paired with an eye shock unconditioned stimulus (UCS). They then received lesions of the middle cerebellar peduncle (MCP) or served as unoperated controls. Following surgery, they were given separate presentations of tone, light, and vibratory CSs, each paired with the eye shock UCS. In this way, conditioned responses (CR) to the previously trained light or tone served as a test of retention, whereas CRs to the remaining two conditioned stimuli (tone and vibratory or light and vibratory) served as a test of acquisition. The results of the study revealed that rabbits with complete lesions of the MCP showed disrupted acquisition and retention of the conditioned NMR to all stimuli, rabbits with partial MCP lesions also showed disrupted acquisition and retention to all CSs, but to a lesser degree, and animals with lesions that missed the MCP and unoperated controls both showed normal acquisition and retention of the conditioned NMR. These data are consistent with the view that the cerebellum is an essential part of the circuit for classical conditioning of the NM response and that information about CSs in the auditory, visual, and tactile modalities reach the cerebellum by way of the MCP.

Afferent Pathways↗
PubMed1987

Results of immunocytochemical, neurochemical, and behavioral studies in aluminum-induced neurofilamentous degeneration.

We undertook a series of experiments designed to further characterize behavioral, neurochemical and immunocytochemical features of aluminum neurotoxicity in the rabbit. Aluminum-exposed rabbits developed learning and memory deficits which were strongly correlated with the degree of whole brain neurofibrillary degeneration (NFD), but not with motor, sensory or motivational factors. Immunocytochemical probes demonstrated that phosphorylated neurofilaments accumulate in neuronal perikarya containing NFD, and double-labelling techniques suggested that NFD affects primarily the projection-type neurons. Finally, the neurochemical profile of the aluminum-intoxicated rabbit showed both similarities and discrepancies to that of Alzheimer's disease (AD).

Aluminum↗
PubMed1986

A selective attention deficit in the rat following induced dopamine receptor supersensitivity.

In the blocking paradigm, prior training to one conditioned stimulus (CSA) blocks the ability to attend to a second conditioned stimulus (CSB) when the two form a compound (CSAB) in subsequent training. Blocking is an associative process by which animals learn to ignore CSB because it contains no new information regarding the reinforcing event. In Experiment 1, dopamine (DA) receptor supersensitivity was induced in rats by prolonged pretreatment with haloperidol. The animals with DA receptor supersensitivity failed to show blocking by responding equivalently to both elements of the CSAB compound. This effect was replicated in Experiment 2, which also tested for an arousal interpretation of disrupted blocking by introducing a novel stimulus following training. Supersensitive rats were no more responsive to this novel stimulus than were control animals, which supports a selective attention deficit interpretation of disrupted blocking with DA receptor supersensitivity. This attentional deficit resembles behavioral perseverations induced by DA agonists.

Animals↗
PubMed1986

Hippocampus and trace conditioning of the rabbit's classically conditioned nictitating membrane response.

Rabbits received classical conditioning of the nictitating membrane response (NMR) in a trace conditioning paradigm. In this paradigm, a 250-ms tone conditioned stimulus (CS) occurs, after which there is a 500-ms period of time in which no stimuli occur (the trace interval), followed by a 100-ms air puff unconditioned stimulus (UCS). In Experiment 1, lesions of the hippocampus or cingulate/retrosplenial cortex disrupted acquisition of the long-latency or adaptive conditioned response relative to unoperated controls and animals that received neocortical lesions that spared the cingulate/retrosplenial areas. When animals with hippocampal or cingulate/retrosplenial lesions were switched to a standard delay paradigm in which the CS and UCS were contiguous in time, they acquired in about the same number of trials as naive rabbits. In a second experiment multiple-unit activity in area CA1 of the hippocampus was examined during acquisition of the trace conditioned response (CR). Three groups of animals were tested: animals that had a 500-ms trace interval (Group T-500), animals that received explicitly unpaired presentations of the CS and UCS (Group UP), and animals that underwent conditioning with a 2,000-ms trace interval (Group T-2000). Animals in Group T-500 acquired the CR in about 500 trials. Early in training, and well before any CRs occurred, there was a substantial increase in neuronal activity in the hippocampus that began during the CS and persisted through the trace interval. There was also an increase in the UCS period that modeled the amplitude-time course of the behavioral unconditioned response. Later in conditioning as CRs emerged, there was no longer neuronal bursting throughout the CS + trace period. Rather, the activity shifted to later in the trace interval and formed a model of the amplitude-time course of the behavioral CR. Activity during the UCS period was similar to that seen earlier in conditioning. Animals in Group UP showed no behavioral conditioning and no increase in neuronal activity. Animals in Group T-2000 showed no long-latency behavioral conditioning and no increase in neuronal activity. The data are discussed in terms of the role of the hippocampus in conditioning during situations in which the CS and UCS are not contiguous in time.

Animals↗
PubMed1985

Age-related disruption of trace but not delay classical conditioning of the rabbit's nictitating membrane response.

Young (6 months of age) and old (36-60 months) New Zealand albino rabbits underwent classical conditioning of the nictitating membrane response in either a delay conditioning (Experiment 1) or a trace conditioning (Experiment 2) paradigm. There was no difference between old and young animals in acquisition of the conditioned response in the delay paradigm, nor were there any age-related differences in generalization to the tone conditioned stimulus (CS) or in sensitivity to the tone CS or eye shock unconditioned stimulus. In the trace conditioning paradigm, however, old animals acquired the conditioned response significantly more slowly than young rabbits. Because the same stimulus parameters and the same response were used in both experiments, it is unlikely that age-related differences in trace conditioning were due to stimulus sensitivity, motivation, or fatigue. The results are discussed in terms of how brain changes that accompany aging could differentially affect these two types of classical conditioning.

Aging↗
PubMed1985

Classical conditioning of the nictitating membrane response in aged rabbits.

There was no difference between old and young animals in acquisition of the conditioned response in the delay conditioning paradigm, nor were there any age-related differences in generalization to the tone CS or in sensitivity to the tone CS or eye shock UCS. In the trace conditioning paradigm, however, old animals acquired the conditioned response significantly slower than young animals. Because the same stimulus parameters and the same responses were used in both paradigms, it is unlikely that the age-related differences in trace conditioning were due to differences in stimulus sensitivity, motor deficits, motivation, or fatigue. Rather, the differences appear due to associative factors. The increased demands of the trace paradigm, which includes a within trial memory component, may be a critical factor in the age related disruption. Moreover, recent data suggest that trace and delay conditioning may involve different neuronal systems (e.g., hippocampus appears necessary for trace but not delay conditioning) and these systems may be differentially effected by the aging process.

Aging↗