Biomedical subjects

P E Sharp

Publications and source records attributed to P E Sharp.

24 records · Page 2Linked to original sources

PubMed1992

Bromide toxicosis (bromism) in a dog treated with potassium bromide for refractory seizures.

A 4-year-old German Shepherd Dog was evaluated because of chronic hind limb lameness and recurrent seizures. Diagnostic evaluation of the dog confirmed rheumatoid arthritis and idiopathic epilepsy. The rheumatoid arthritis was treated with prednisone and piroxicam. The seizures were treated with phenobarbital plus clonazepam. The seizures were refractory and potassium bromide was substituted for clonazepam. The dog was reevaluated 4 months after initiation of potassium bromide treatment because of recurrence of arthritis signs. During hospitalization, the dog had neurologic signs, which progressed from depression to recumbency and stupor. Anisocoria, muscle pain, and hyporeflexia were noticed. Bromide toxicosis was diagnosed on the basis of toxic serum bromide concentration (2.7 mg/ml; therapeutic range, 1.0 to 2.0 mg/ml). Following cessation of potassium bromide treatment, the neurologic signs resolved. The seizures recurred 6 weeks after potassium bromide was discontinued. Bromide treatment was reinitiated at half the initial dosage. After 6 weeks, the serum bromide concentration was 1.9 mg/ml, and no seizures had been reported by the dog's owners. Therapeutic serum bromide concentrations in dogs has been reported to be 0.5 to 2.3 mg/ml. The serum bromide concentration at which toxic signs are expected is variable in human beings because individuals differ in their tolerance of the drug. Clinical trials are necessary to determine the toxic serum bromide concentrations in dogs. This case of bromism in a dog suggests that the dosage of potassium bromide should be based on serial measurement of serum bromide concentrations.

Animals↗

PubMed1992

Evidence for NMDA receptor involvement in environmentally induced dentate gyrus plasticity.

Research has demonstrated environmentally induced plasticity of hippocampal dentate gyrus-evoked potentials. Other research has shown a role of the NMDA receptor in dentate gyrus long-term potentiation (LTP). The authors tested the role of the NMDA receptor in one form of environmentally induced plasticity, in which transferring animals from their home cages to another environment results in significant excitatory postsynaptic potential (EPSP) enhancement and concomitant depression of the population spike. Rats were chronically implanted with stimulating electrodes in the perforant path and recording electrodes in the dentate gyrus bilaterally. Evoked potentials were recorded from freely behaving rats for four 20-minute sessions (1/wk), which took place immediately following an environmental transfer. Rats received 0.00, 0.05, 0.08, or 0.10 mg/kg MK-801 s.c. 30 minutes prior to recording sessions in either an ascending- or descending-dose series. Results showed that MK-801 produced a reduction of the EPSP enhancement, which takes place over the 20-minute session. The effects of MK-801 on spike depression varied as a function of dose series and time within a session, suggesting a long-term effect of MK-801 on spike depression. There was no detected effect of MK-801 on behavior. Results suggest a role of the NMDA receptor in this form of environmentally induced plasticity with different effects of NMDA receptor antagonism on EPSP enhancement and spike depression.

Animals↗

PubMed1990

Firing properties of hippocampal neurons in a visually symmetrical environment: contributions of multiple sensory cues and mnemonic processes.

The location-specific firing of hippocampal place cells can easily be brought under the control of experimenter-defined cues. Nevertheless, there is evidence that these firing fields are not determined just by immediate sensory input, but also by earlier states of the nervous system (O'Keefe and Speakman, 1987). Here, we report further on the roles of multiple visual cues and mnemonic processes in determining the firing of place cells. Rats were trained to chase food pellets in a cylinder with homogeneous gray walls and 1 white cue card. After a cell's field was recorded in this "standard" condition, probe sessions were conducted in which a second card was placed 180 degrees away from the first. This configuration created a diametrically symmetrical environment in which pairs of locations 180 degrees apart were identical with respect to views of the wall and cards. If place cells are strongly controlled by these immediately available views, firing in the 2-card configuration should be diametrically symmetrical. Alternatively, because the rat moves freely in the cylinder, information is available that pairs of visually identical places are not truly the same. If some mnemonic process stores and updates information about the rat's paths during the session, it is possible that the firing pattern will be different in 2 such places, especially because the original training was conducted in the 1-card, asymmetrical environment. Thirteen of 18 cells had a single, asymmetric firing pattern after the second card was introduced; the field was the same size and shape as in the 1-card configuration and in the same spatial relation to 1 of the 2 cards. The field position during 2-card sessions could be rotated 180 degrees by starting the rat by one card or the other. In further probe sessions in which the cue cards, entry location, and background cues were, in various combinations, rotated in relation to each other, these cells always showed a single field, similar in size and shape to that in the standard, and in the same relationship as in the standard to as many cues as possible. The remaining 5 cells showed complex changes over repeated 2-card sessions, and 3 of these showed paired fields, 180 degrees apart for at least some of the sessions. In one case, the second field disappeared with repeated exposures to 2 cards; in another, the second field persisted when only 1 card was used. We conclude that place cells are influenced both by the immediate sensory configuration and by internal neural states related to earlier experience in the environment.

Action Potentials↗

PubMed1987

Effects of aging on environmental modulation of hippocampal evoked responses.

Evoked responses in the dentate gyrus of the hippocampal formation undergo a long-term enhancement following high-frequency stimulation of the perforant pathway. A similar change results from exposure of animals to a complex spatial environment. The effect of aging on the development and decay of this environmentally induced response enhancement was examined in the present study. Previously it was shown that electrically induced enhancement reaches the same asymptotic level in young and old animals but decays more quickly in old animals. It has been suggested that this faster decay may underlie the faster forgetting of spatial information observed in old animals. Chronic recordings were made from young (14 month) and old (32 month) rats. After exposure to an enriched environment for 11 days, the population spike component of the response increased about 125% over baseline in both groups. No changes were seen in either group in the synaptic component. Following the enrichment treatment, animals were returned to their home cages. The decay of the enhanced population spike during this period differed markedly between age-groups (time constants of 30 and 11 days for the young and old groups, respectively). These results suggest that the factors governing the decay of electrically and environmentally induced response enhancement are similarly affected by the aging process and may share a common mechanism.

Afferent Pathways↗

PubMed1985

Enhancement of hippocampal field potentials in rats exposed to a novel, complex environment.

The hippocampus plays a crucial role in place learning in rodents and also exhibits a long-term enhancement of synaptic strength and postsynaptic excitability following electrical stimulation of its principal afferents. In the present report we suggest that these two observations may be related, by demonstrating an increase in synaptic and postsynaptic field potential amplitudes resulting from exposure to a spatially complex environment.

Animals↗

PubMedDate not supplied

Multiple spatial/behavioral correlates for cells in the rat postsubiculum: multiple regression analysis and comparison to other hippocampal areas.

Head direction cells in the rat postsubiculum fire in relation to the momentary directional heading of the animal, with each cell firing only when the animal faces in one particular direction. To understand how this signal might be generated, one useful step is to discover what other cell types, in addition to the head direction cells, may exist in the postsubiculum, since these cells might be involved in helping to generate the direction-specific activity. Here postsubicular cells were recorded as animals navigated in a cylindrical recording chamber. It was found that, in addition to head direction cells, the postsubiculum contains cells that show several other types of spatial/behavioral correlates, including angular velocity of the head, running speed, and location. Ten percent of the cells were classified as angular velocity cells, and they resembled vestibular afferent fibers, with antagonistic responses to clockwise versus counterclockwise turns. In addition, numerous other cell types were observed. These latter cells were harder to classify, but all showed a significant correlation with one or more of the above variables. These findings suggest that the head direction cell signal may be at least partly based on the angular velocity, running speed, and locational signals observed here.

Animals↗