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Biomedical subjects

R J Racine

Publications and source records attributed to R J Racine.

At least 19 recordsLinked to original sources

Kindling causes changes in the composition of the astrocytic cytoskeleton.

Changes in the astrocytic cytoskeleton were examined in amygdala kindled rats using immunocytochemical techniques. One week following kindling, there was a dramatic increase in immunoreactivity to glial fibrillary acidic protein and vimentin in astrocytes throughout amygdala, pyriform cortex and hippocampus bilaterally. Since these changes occurred in anatomical sites involved in the propagation of kindled seizures, the observed cytoskeletal reorganization in astrocytes may signify important functional alterations in the kindled brain.

Amygdala

Kindling-induced potentiation in the piriform cortex.

At intensities sufficient to induce epileptiform afterdischarges, repeated electrical stimulation of limbic structures can lead to the development of permanent increases in the strength of the epileptiform response (kindling). Field potentials evoked by pulse stimulation are also increased in amplitude in a number of forebrain pathways following kindling. This kindling-induced potentiation effect is similar in many respects to the 'long-term potentiation' (LTP) effect which is produced by non-epileptogenic stimulation. There are, however, some interesting differences. For example, kindling-induced potentiation can far outlast LTP. In these experiments, we attempted to determine the longevity of the kindling-induced potentiation of the response evoked in the piriform cortex by olfactory bulb stimulation, following olfactory bulb kindling. This system was targeted because both the olfactory bulb and the piriform cortex are highly reactive kindling sites. In addition, we used the paired pulse technique to monitor facilitation and inhibition in this system. Kindling was found to induce a potentiation in the piriform field potential that lasted for at least 3 months (the period of the experiment) with little or no decay. Kindling also produced a decrease in paired pulse facilitation. In some animals the net facilitation was changed to a net depression. These results are consistent with the interpretation that kindling produces an increase in recurrent inhibition in the piriform cortex. The paired pulse measures, however, returned to near baseline levels over the 3-month test period.

Animals

Activation of the NMDA receptor: a correlate in the dentate gyrus field potential and its relationship to long-term potentiation and kindling.

Stimulation trains, but not stimulation pulses, are capable of inducing long-term potentiation (LTP). In this paper we report experiments designed to examine, in chronic preparations, the characteristics of a component unique to the train-evoked response. Stimulation trains applied to the perforant path evoked population EPSP's and population spikes in the dentate gyrus that were nearly identical to those evoked by single pulses of comparable intensity. The trains also triggered a prolonged potential, negative at the dendritic pole of our electrodes, which far outlasted the pulse-evoked response. We substracted pulse-evoked responses from these train-evoked responses which left us with a waveform that peaked at about 15 ms and lasted for about 50-70 ms. The GABA agonists, diazepam and sodium pentobarbital, had no significant effect on this component, but the NMDA antagonists, ketamine and MK-801, both depressed it by over 30%. The late component had a very low threshold, which might account for the frequent observation of LTP induction at very low thresholds. Also, the late component is reliably seen in all animals showing LTP, even in the occasional animals that show no population spikes. The late component did not appear to be affected by the induction of LTP, and was either not affected or was depressed following the completion of kindling. When the 'NMDA-component' of the train-evoked response was monitored, along with LTP, in an ascending intensity train series, it was found that both the NMDA-component and the LTP increased smoothly. There was no sudden appearance of the NMDA-component at the LTP threshold. The presence of an NMDA component in the field potential of the chronic preparation allows the monitoring of the levels of NMDA activation over prolonged periods.

Action Potentials

Maintenance on L-deprenyl prolongs life in aged male rats.

The effect of l-deprenyl on longevity was examined in male Fischer rats. Subcutaneous injections of either l-deprenyl (0.25 mg/kg) or saline were given every other day starting at 23 to 25 months of age. The deprenyl-treated animals showed a significant increase in both mean and maximum survival. The differences were largest in the longest surviving animals, suggesting that an earlier onset for treatment may be beneficial. Analysis of body weights ruled out deprenyl-induced dietary restriction as an explanation for the group differences in survival. To the contrary, after about four months of treatment, the animals of l-deprenyl showed a slower rate of decrease in body weight than the controls.

Aging

Perceived pitch class of isolated musical triads.

A paired-comparisons task was used to determine which note of a pure-tone triad sounded most similar to the triad. Musically inexperienced Ss showed no systematic preference, experienced Ss consistently preferred the highest note in the triad, and professional musicians split equally between preferring the highest note and the root note. Preference for the root note shifted to preference for the highest note as the triad type became increasingly inharmonic, suggesting that the former depended on inference of a missing fundamental. When Ss were asked to vocally reproduce the pitch they heard when listening to a triad, similar results were obtained, except that a root-note preference was not detectable in Ss with less musical experience. Preference for the root note was also facilitated by use of octave-replicated tones, and this increase was shown to be due to obscuring of pitch-height cues, rather than harmonic complexity.

Adult

Pitch interactions in the perception of isolated musical triads.

In previous work done in our laboratory, we have investigated the perceived pitch class of isolated musical triads. We have found that as the amount of musical training increased, listeners perceptions progress, from very confused percepts of pitch class, to analytic percepts corresponding to the pitch class of the highest note in the triad, and finally to synthetic percepts corresponding to the root note for the more harmonic triad types. In the present work, we used a pitch matching technique to determine the actual pitch, rather than merely the pitch class, perceived when listeners analytically "hear out" a particular note in a major triad. There was a strong tendency for the pitch of the analytically perceived note to be displaced by as much as 60 cents in the direction of the other notes in the triad. The magnitude of this effect decreased as musical training increased, and it was also affected by the relative salience of the individual triad notes. These results have implications for the mechanism of triad perception, and for claims regarding the harmonic equivalence of triad inversions.

Adolescent

Effects of phenytoin, carbamazepine, and clonazepam on cortex- and amygdala-evoked potentials in partially kindled rats.

The kindling technique has been reported to produce a long-lasting enhancement in both the early and late phases of evoked potentials triggered from the kindled focus. It also alters paired-pulse facilitation and depression in the pathways which support these phenomena. The present experiment was designed to determine whether the drugs which antagonize secondary generalization in the kindling model also antagonize kindling-enhanced excitation in the pathways leading out of the focus. Multiple doses of phenytoin, carbamazepine, and clonazepam were therefore tested against single- and double-pulse evoked potentials triggered from the focus in rats that had been subjected to parital kindling from either the amygdala or the cortex. Responses were recorded in monosynaptic sites and in the mesencephalic reticular formation--a polysynaptic site thought to play an important role in secondary generalization. No drug-related effects were found on early evoked potential components, either in the single-pulse or the double-pulse paradigm. Kindling-enhanced late components ("late waves"), however, were clearly and selectively antagonized by clonazepam.

Amygdala

The role of the pyriform cortex in the generation of interictal spikes in the kindled preparation.

The development of interictal spikes (IIS) was monitored during amygdala or pyriform cortex kindling in a series of 4 experiments. It was found that (1) spike-like transients were often present in the pyriform cortex EEG before kindling had begun; (2) these transients developed progressively into large amplitude and complex IIS as kindling proceeded; (3) the pyriform cortex IIS continued to show the greatest proportion of earliest onset spikes in most animals after kindling was completed; (4) other sites (including the ventral, but not the dorsal hippocampus) gradually developed the capacity to generate IIS as kindling progressed; (5) although specific sites within the pyriform cortex may serve as a generator, their location along the longitudinal axis of the pyriform lobe varied from animal to animal (and did not appear to depend upon the location of the kindling electrode); (6) although there often appeared to be 2 spike types, based on the polarity of the first component, there were also transitional waveforms, raising the possibility that they were variations on a single spike type, and (7) the IIS were often preceded, usually in the pyriform cortex, by reliable pre-spike events (smaller spikes or a 'ripple' on the EEG).

Amygdala

The effects of various lesions and knife-cuts on septal and amygdala kindling in the rat.

Large bilateral aspiration lesions of the hippocampus had no significant effect on septal kindling, whereas large bilateral DC lesions of the pyriform lobe resulted in a small but significant increase in the number of septal stimulations required to complete kindling. Bilateral aspiration lesions of the dorsal hippocampus or large bilateral DC lesions of the ventral hippocampus had no effect on amygdala kindling. Small DC lesions of the stria terminalis significantly facilitated amygdala kindling. Unilateral or bilateral ventral knife-cuts delivered in a coronal plane anterior to the amygdala, disrupting communication with anterior pyriform structures, produced a small but nearly significant increase in the number of stimulations required for amygdala kindling. Similar cuts placed posterior to the amygdala, disrupting communication with the hippocampus, significantly facilitated kindling. Cuts that were medially placed, to disrupt the ventral amygdala-fugal pathway, had no effect on amygdala kindling. These results show that the hippocampus is not critical for either septal or amygdala kindling. The pyriform lobe structures appear to play a facilitatory role in kindling, but none of the lesions or knife-cuts were capable of blocking or even severely retarding kindling.

Amygdala

The development and decay of kindling-induced increases in paired-pulse depression in the dentate gyrus.

Epileptogenic stimulation (kindling) leads to an increase in recurrent inhibition in the dentate gyrus, possibly due to an increase in benzodiazepine receptors. A second, late inhibitory component also potentiates as a result of kindling. In the present experiments, the time course of the development and decay of this kindling-induced increase in inhibition was studied. Rats were kindled by stimulation of the perforant path or by direct stimulation of the dentate gyrus. Paired-pulse stimulation was applied to the perforant path and field potential measures were taken within the dentate gyrus. These procedures allowed the monitoring of inhibitory events in chronic preparations over prolonged periods. Input/output measures of the baseline responses were also monitored during the course of, and after the completion of kindling. The increase in the early component (about 20-50+ ms) of paired-pulse depression was seen after the first kindling stimulation. The increase in the late component of depression (about 100-500+ ms) did not develop until after about 10 stimulations had been delivered. The late component then decayed more rapidly than the early component after the completion of kindling. The baseline response also showed some indication of depression, particularly in the dentate gyrus kindled group, raising the possibility that feedforward inhibition had also been potentiated.

Animals

Interactions between septal and entorhinal inputs to the rat dentate gyrus: facilitation effects.

We examined facilitation effects between the medial septum and perforant path inputs to the dentate gyrus for the four possible combinations of paired-pulse activation. Facilitation effects occurred in all cases. The largest facilitation effects occurred when the septal pulse served as the conditioning pulse for the population spike subsequently evoked by a perforant path pulse. Using 3 pulses, we also examined the influence of septal activation on paired-pulse facilitation of the perforant path-granule cell population spike. A septal stimulation pulse, applied 6-10 ms prior to the onset of the population spike evoked by a perforant path conditioning pulse, did not affect the perforant path-dentate test response at any interpulse interval. If the septal pulse occurred immediately prior to population spike onset, however, there was a significantly greater depression of the test response from 70-3000 ms, but no effect at early intervals (20-50 ms). The effect of the septal pulse appears more consistent with a direct action of the septal terminals on granule cells than with an indirect action via the recurrent inhibitory interneurons.

Animals

Long-term potentiation in the interpositus and vestibular nuclei in the rat.

Previous unpublished experiments from this laboratory had revealed only post-activation depression effects in the cerebellar cortex when its inputs were activated by high frequency trains. In the experiments reported in this paper, we found reliable long-term potentiation (LTP) effects in the deep nuclei (interpositus and vestibular) when stimulation trains were applied to the white matter at the point where inferior peduncle fibers enter the cerebellum. LTP effects were found in both acute and chronic preparations. In the chronic preparations, LTP lasted for at least 8 days in all but one animal.

Animals

Epileptiform burst responses in ventral vs dorsal hippocampal slices.

Field potentials from area CA1 evoked by stimulation of the Schaffer collaterals were compared in dorsal and ventral hippocampal slices of rat brain. Responses were categorized into 5 response types on the basis of their morphology, ranging from simple (single spike component) to complex (multiple spike components). A higher percentage of ventral slices, compared to dorsal slices, responded with a complex morphology under normal and increased K+ concentrations. Thus, there was a significantly greater tendency for cells within the ventral hippocampus to generate burst responses.

Animals

Barbiturate-enhanced paired-pulse depression in neonatal rats.

Paired-pulse depression of the population spike in the hippocampal formation of barbiturate anaesthetized mature rats is increased compared to that in urethane unanaesthetized rats. This barbiturate-induced increase in depression is greatly enhanced in immature animals, which are also known to be behaviorally more sensitive to barbiturates. These results suggest an increased sensitivity of the recurrent inhibitory (possible GABAergic) system to barbiturates in the immature central nervous system.

Age Factors

The effects of repeated induction of long-term potentiation in the dentate gyrus.

Previous experiments have shown that long-term potentiation (LTP) generally lasts for only a few days or weeks. The LTP phenomenon would be more attractive as a memory model if it were more enduring. The experiments reported in this paper were designed to test the effects of repeated induction of LTP on the duration of LTP. Three groups of animals received 5 LTP-inducing stimulation sessions. In one group of animals, the stimulation sessions were administered every 24 h. In the 2nd group, the sessions were administered after the LTP effects had decayed to 50% of the peak values. In the 3rd group, the sessions were administered only after the response amplitudes had completely returned to pre-LTP baseline levels. None of the LTP measures were altered, in any group, as a result of repeated induction of LTP. The thresholds, the asymptotic levels of potentiation, and the decay rates were the same after each session. Other treatments may alter the duration of LTP effects, but repeated induction of LTP does not appear to have any lasting effects.

Animals