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J S Stripling

Publications and source records attributed to J S Stripling.

At least 19 recordsLinked to original sources

Potentiation of late components in olfactory bulb and piriform cortex requires activation of cortical association fibers.

Previous research has demonstrated that repeated high-frequency stimulation of the granule cell layer of the olfactory bulb (OB) produces an enduring potentiation of late components (PLC) in potentials evoked in the OB and piriform cortex (PC), while leaving the monosynaptic EPSP produced by OB mitral cells in PC pyramidal cells unaltered. Two experiments were conducted using male Long-Evans rats with chronically implanted electrodes to assess the relative contribution to this potentiation of the two main fiber systems that interconnect the OB and PC: the lateral olfactory tract (LOT), which contains mitral cell axons that synapse on PC pyramidal cells, and the PC association fiber system, which consists of the axons of PC pyramidal cells that synapse on several cell populations within the PC and on granule cells in the OB. The results indicate that stimulation of PC association fibers is both necessary and sufficient to duplicate the pattern of potentiation seen following OB stimulation in previous experiments. LOT stimulation had no consistent effect, and coactivation of the LOT and PC association fibers was no more effective than activation of PC association fibers alone. Possible mechanisms underlying this effect are discussed, including (1) long-term potentiation (LTP) at synapses made by the axons of PC pyramidal cells on neurons in the OB and PC; and (2) repetitive firing in PC pyramidal cells due to regenerative excitation in a population of deep cells in the PC and endopiriform nucleus.

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Functional correlates of selective long-term potentiation in the olfactory cortex and olfactory bulb.

High-frequency stimulation of the granule cell layer of the olfactory bulb (OB) has previously been shown to result in a selective long-term potentiation (LTP) of late components of potentials evoked in the OB and piriform cortex (PC). The functional impact of this potentiation was explored in male Long-Evans rats with chronically implanted electrodes by comparing the effects of paired-pulse stimulation of the OB in potentiated and control animals. Effects were examined on two components of the potential evoked in the PC: A1, which represents the population EPSP produced by OB mitral cells in PC pyramidal cells via the lateral olfactory tract (LOT), and B1, which represents the subsequent population EPSP produced by PC pyramidal cells in other pyramidal cells. Two separate functional correlates of selective LTP were found. First, there was enhanced paired-pulse depression of B1, indicating increased inhibition of PC pyramidal cells. Second, there was a shift from paired-pulse facilitation to depression of A1, which was accompanied by a decrease in amplitude of the LOT volley, indicating that fewer mitral cells were activated by the stimulation. This shift was most prominent in animals with stimulating electrodes closest to the mitral cell layer, suggesting that it is dependent upon direct stimulation of mitral cell somata. These observations, together with other results reported in the manuscript, support the conclusion that there is an enhanced inhibition of mitral cells following selective LTP. Thus a primary consequence of selective LTP appears to be enhanced inhibition of principal neurons in both the PC and OB. These findings are consistent with our previous proposal that selective LTP represents potentiation at excitatory synapses made by PC pyramidal cells on inhibitory interneurons in the PC and OB.

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Characterization and anatomical distribution of selective long-term potentiation in the olfactory forebrain.

High-frequency stimulation of the granule cell layer of the olfactory bulb (OB) has previously been shown to result in a form of long-term potentiation in the piriform cortex (PC) that is selective to late components of the potential evoked in the PC58. This phenomenon was explored in male Long-Evans rats with chronically implanted electrodes by recording potentials evoked in the OB and in various sites in the ipsilateral and contralateral PC before and after repeated high-frequency stimulation of the OB. Recordings at all sites exhibited a gradually developing potentiation that was selective to late components of the evoked potential. In the OB and ipsilateral PC this potentiation had an overt long-term component that lasted for days, and all sites exhibited a latent potentiation that enabled the reestablishment of substantial levels of potentiation by mild patterns of stimulation that had no effect in control animals. No potentiation of the population EPSP representing input from the lateral olfactory tract to the PC was seen. Available evidence concerning the neuronal elements activated by the stimulation and the neuronal events likely to underlie the potentiated components of the evoked potentials suggests that this potentiation may represent an enhancement of inhibitory interactions within the PC and between the PC and OB.

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Twenty-four-hour post-seizure inhibition during limbic kindling requires seizure generalization.

Male Long-Evans rats were kindled by stimulation of the pyriform cortex using an afterdischarge (AD) threshold procedure that triggered one AD every 24 h. AD threshold dropped rapidly as long as the seizures remained localized, reaching an asymptote of 30% of its initial value by the 6th AD. In contrast, AD threshold rose progressively across the first six generalized seizures (i.e. ADs accompanied by forelimb clonus). This elevation in threshold was dependent upon the daily elicitation of a generalized seizure, and the threshold returned to its previous low value after 4 seizure-free days. This indicates that post-seizure inhibition in the pyriform cortex is a transient response produced by generalized seizures and is not related to the relatively permanent changes that underlie kindling.

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Effect of cocaine and lidocaine on the development of kindled seizures.

The effect of a subconvulsive dose of cocaine or lidocaine on the development of kindling was studied in male Long-Evans rats. Animals were divided into three groups and kindled by daily electrical stimulation of the pyriform cortex. Fifteen minutes before each stimulation each animal received an intraperitoneal injection of either saline, 20 mg/kg cocaine hydrochloride, or 20 mg/kg lidocaine hydrochloride. Following kindling the drug treatment was discontinued and the transfer of kindling to a nondrug state was assessed by test stimulations given 2, 6, and 48 days after the last day of kindling. Both cocaine and lidocaine dramatically accelerated the development of kindling. Furthermore, the duration of clonus at kindling criterion was significantly longer in lidocaine-treated animals than in animals treated with saline, and the onset of clonus in cocaine-treated animals occurred significantly sooner after stimulation. However, this performance did not transfer fully to the nondrug state, with some animals failing to exhibit clonus. Among those animals exhibiting clonus at nondrug tests, afterdischarge duration was significantly higher in cocaine-treated than in saline-treated animals, but clonus duration was no longer elevated in lidocaine-treated animals, and the latency to clonus rose dramatically in animals previously treated with either cocaine or lidocaine. These results indicate that a subconvulsive dose of cocaine or lidocaine can facilitate the development of kindling when the drug is active at the time of electrical stimulation, apparently by means of the local anesthetic action shared by the two drugs. The kindling produced in this fashion is not entirely equivalent to kindling produced by electrical stimulation alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selective long-term potentiation in the pyriform cortex.

Electrical stimulation of the olfactory bulb (OB) produces an evoked potential in the pyriform cortex (PC) characterized by an initial surface-negative wave (period 1) representing activation of PC pyramidal cells via the lateral olfactory tract, followed by a surface-positive wave (period 2) which is temporally associated with recurrent and feed-forward inhibition. The experiment reported here examined the changes that occur in the PC evoked potential following a pattern of stimulation that has been found to produce short- and long-term potentiation (LTP) in other areas of the forebrain. Male Long-Evans rats with electrodes in the OB and PC were divided into two groups. LTP animals received high-frequency stimulation of the OB (30 trains of 10 pulses each at a frequency of 100 Hz). Control animals received the same number of pulses at a lower frequency (1 Hz). This procedure was repeated 6 times at 2-day intervals. Neither high- nor low-frequency stimulation altered period 1 of the PC evoked potential, indicating that synaptic input arriving via the lateral olfactory tract was unaffected. However, LTP animals exhibited a marked increase in the amplitude and duration of period 2 which appeared to reflect two separate processes: a short-term change that peaked within 30 min of the trains; and a long-term change that accumulated across the 6 treatments. LTP of period 2 persisted in latent form for at least 32 days after the last treatment. Control animals exhibited only small changes that were attributed to the paired-pulse stimulation used for testing rather than the 1 Hz Control trains. These results suggest that repeated high-frequency stimulation of the OB causes a persistent alteration in the way information is processed within the PC. The form of LTP demonstrated here is markedly different from that found in the hippocampal formation, where potentiation of the monosynaptic excitatory postsynaptic potential is a prominent effect. The functional significance of this change cannot be determined with certainty from the present experiment, but available evidence suggests that it represents an enhancement of inhibitory processes within the PC.

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Effect of pentylenetetrazol-induced convulsions on the development and expression of limbic kindled seizures.

Male Long-Evans rats experienced three convulsions induced by intravenously administered pentylenetetrazol (PTZ) and were then kindled by electrical stimulation of the olfactory bulb or amygdala. Pretreatment with PTZ did not alter the rate of kindling in either site but did enhance the expression of kindled seizures once generalization had occurred (PTZ-treated animals had significantly longer motor seizures, measured by clonus duration, than did saline-treated controls). This suggests that PTZ-induced convulsions have selective effects on areas of the brain that are involved in the expression of the motor seizure. In addition, rats treated with PTZ after kindling had convulsions that were significantly longer in duration than any of their three pre-kindling convulsions, indicating that kindling produced an increased sensitivity to PTZ's convulsant effects. Comparison of this experiment with previous research suggests that the ability of a drug treatment to generate a kindling-like effect is related to the pattern of seizure activity that it produces.

Amygdala↗

Effect of olfactory bulb kindling on evoked potentials in the pyriform cortex.

The potential evoked in the pyriform cortex by single-pulse stimulation of the olfactory bulb was examined before and after single and repeated elicitation of an epileptiform afterdischarge produced by stimulation of the olfactory bulb. A single afterdischarge (AD) produced a rapid (i.e. within 5 min) increase in the amplitude of an early surface-negative wave and duration of a later surface-positive wave. These effects persisted at least 48-72 h. Repeated elicitation of ADs resulted in kindling. A large increase in the amplitude of a later surface-negative wave (approximately 25 ms latency) occurred during kindling. This wave remained significantly elevated for at least 72 h after the last AD. Long-term potentiation of the early surface-negative wave was produced by kindling or two focal ADs. A short-term effect which was consistently observed following a focal or generalized AD was a prolongation of a late surface-positive wave. These effects are discussed in relation to long-term potentiation, postseizure inhibition, and kindling development.

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Monoaminergic and local anesthetic components of cocaine's effects on kindled seizure expression.

Male Long-Evans rats were kindled via daily electrical stimulation of the left prepyriform cortex. The animals were then used in two experiments which examined the pharmacological basis of cocaine's effects on three mutually exclusive components of the kindled seizure, which were the following: (a) latency to clonus, (b) clonus duration, and (c) duration of AD outlasting clonus. The first experiment compared the effects produced by cocaine HCl (20 mg/kg, IP), lidocaine HCl (20 mg/kg, IP), and amphetamine sulfate (2.5 mg/kg, IP). The results indicated that both cocaine and lidocaine reduced the duration of kindled AD, latency to clonus, and duration of AD persisting beyond clonus, thus suggesting that these cocaine effects are mediated by local anesthetic mechanisms. Only cocaine reduced clonus duration, which suggests that this cocaine effect is not produced by a local anesthetic action. The second experiment examined the effects of cocaine following the administration of three dose levels of the monoamine antagonists haloperidol, prazosin, yohimbine, propranolol, or metergoline (selected for their ability to block dopamine, alpha-1-norepinephrine, alpha-2-norepinephrine, beta-norepinephrine, and serotonin receptors, respectively). The results of this experiment found no support for a monoaminergic contribution to cocaine's effect on clonus latency or AD after clonus. However, results for prazosin, which reduced clonus duration and exhibited an additive effect with cocaine on this variable, suggest that cocaine's norepinephrine action (especially on the alpha-norepinephrine systems) may modulate clonus duration.

Amphetamine↗

Effect of cocaine and pentylenetetrazol on cortical kindling.

The effect of drug-induced convulsions on subsequent cortical kindling was studied in male Long-Evans rats. Animals experienced three intravenous infusions of physiological saline at 3 day intervals, or three convulsions induced by the infusion of cocaine or pentylenetetrazol (PTZ). Beginning eight days after the last infusion, all animals were kindled by stimulation of the anterior neocortex (area 6). PTZ-induced convulsions facilitated the development of both the behavioral convulsion and the electrographic seizure during cortical kindling, while cocaine-induced convulsions facilitated only the development of the electrographic seizure. Comparison of these results with previous research indicates that convulsions induced by these two drugs have long-lasting effects on brain function which differ both in their anatomical distribution and in the nature of the effects produced. These drugs also differed in their acute effects at subconvulsant doses on the expression of cortically kindled seizures. Cocaine (and lidocaine, another local anesthetic) substantially elevated afterdischarge (AD) threshold and inhibited the focal component of the cortically kindled seizure. PTZ had no significant effect on either of these variables but significantly increased AD duration. In addition to these drug effects, a substantial inhibitory effect on seizure expression was observed, both during kindling and afterwards, when ADs were elicited daily but not when they were separated by 3 days or more. This finding suggests that the large number of ADs typically required for cortical kindling may be due in part to daily stimulation.

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Cocaine and "pharmacological kindling" in the rat.

The concept of "pharmacological kindling" has been used to explain the behavioral sensitization to cocaine produced by repeated administration of subconvulsive doses. This idea was tested by the repeated administration of cocaine to rats followed by electrical kindling of the olfactory bulb (a site at which cocaine has prominent electrophysiologic effects). No significant effect of cocaine on kindling was found. The relationship of this finding to studies using other drugs is discussed.

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Origin of cocaine- and lidocaine-induced spindle activity within the olfactory forebrain of the rat.

Cocaine and other local anesthetics produce a characteristic form of electrical activity in the olfactory forebrain consisting of bursts of sinusoidal potentials (spindles) in the range of 20-50 c/sec. The purpose of the present experiment was to determine if this drug-induced spindle activity is generated by the same neuronal elements in the olfactory bulb (OB) and prepyriform cortex (PPC) which generate naturally occurring olfactory spindles. Rats with chronically implanted electrodes in the OB and PPC were injected with doses of cocaine or lidocaine hydrochloride sufficient to produce spindles (5 mg/kg i.v. or 40 mg/kg i.p.). Drug-induced and naturally occurring spindles exhibited similar anterior-posterior amplitude profiles, with the highest amplitude in the OB and the lowest in the posterior PPC. Multipolar recordings from the PPC indicated that the amplitude of naturally occurring and drug-induced spindles was highest at sites near the superficial pyramidal cell layer of the PPC and lower at sites 1-2 mm more dorsal. Furthermore, both naturally occurring and drug-induced spindles exhibited a polarity reversal near the superficial pyramidal cell layer of the PPC and the mitral cell layer of the OB. Finally, neither form of spindle occurred when nasal air flow (olfactory stimulation) was prevented. These observations suggest that cocaine- and lidocaine-induced spindles are generated in the OB and PPC by the same neuronal elements which also produce naturally occurring olfactory spindles.

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Effect of cocaine on afterdischarge threshold in previously kindled rats.

Previous experiments have yielded conflicting reports on the effect of cocaine on the after discharge (AD) threshold for electrical stimulation. The present study was designed to determine if differences in the type of stimulation used could account for these discrepancies. Male Long-Evans rats which had been previously kindled by stimulation of the olfactory bulb were used to determine the AD threshold of the olfactory bulb following the intraperitoneal injection of saline or 20 mg/kg cocaine hydrochloride. AD's were elicited by trains of square-wave pulses which varied in frequency and train duration. Cocaine significantly increase the amount of current required to produce AD's using stimulus trains with frequencies of 30-100 pulses/sec, while evidence of a decrease in AD threshold by cocaine was found at a frequency of 20 pulses/sec. The results suggest that cocaine has opposite effects on AD threshold at high and low frequencies of stimulation.

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Facilitation of kindling by convulsions induced by cocaine or lidocaine but not pentylenetetrazol.

The effect of drug-induced convulsions on kindling was studied in male Long-Evans rats. In Experiment 1 rats experienced a single convulsion induced by the intravenous infusion of cocaine, lidocaine, or pentylenetetrazol (PTZ), or received a control infusion of saline. Beginning eight days later all animals were kindled by daily stimulation of the olfactory bulb. Animals which had been convulsed by cocaine or lidocaine kindled significantly faster than either saline controls or PTZ-convulsed animals, which did not differ significantly. Experiment 2 was conducted to determine if an effect of PTZ on kindling could be obtained with repeated convulsions. Rats experienced three convulsions induced by cocaine or PTZ at 72 hr intervals, or control infusions of saline. Kindling began on the eighth day after the last infusion. Cocaine-convulsed animals again kindled significantly faster than saline or PTZ-convulsed animals, which did not differ significantly. The cocaine animals also had significantly longer afterdischarges than the saline group at the end of kindling and when stimulated again 21 days after kindling was completed. These results suggest that the facilitating effect of cocaine-induced convulsions is not a general property of all convulsants but is a more specific effect which is apparently shared by other local anesthetics.

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A simple intravenous catheter for use with a cranial pedestal in the rat.

A catheter design and implantation technique are described which permit the repeated infusion of drugs into the external jugular vein of the rat. The catheter is designed specifically for use when electrode implantation or other surgery requires the construction of a cranial pedestal from dental acrylic. The speed and simplicity of the catheter's construction and implantation are advantageous, and it performs reliably for several months after implantation.

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