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D C McIntyre

Publications and source records attributed to D C McIntyre.

At least 55 records · Page 3Linked to original sources

Facilitation of secondary site kindling in the dorsal hippocampus following forebrain bisection.

Bisection of the corpus callosum and hippocampal commissure, after the kindling of one dorsal hippocampus (primary site), had no effect on the rate of generalized kindled seizure development in the contralateral dorsal hippocampus (secondary site). The rate of kindling in the secondary site was very rapid in both intact and commissure-bisected rats, resulting in a positive transfer between the two sites of approximately 90%. In addition, the afterdischarge threshold response of the secondary site, after commissurotomy but before secondary site kindling, revealed mature local epileptogenesis. These observations support the suggestion that the positive transfer observed between the dorsal hippocampi is based on bilateral epileptogenesis during primary site kindling. Bisection of the anterior corpus callosum lateralized the forelimb convulsion while the hippocampal commissure independently mediated the laterality of the hippocampal afterdischarge. Commissurotomy had no significant influence on the latency to onset or offset of these motor and electrographic responses. These results are compared with those from the amygdala, and their implication for the laterality of epileptogenesis is discussed.

Animals↗

Power spectral analysis of electroencephalographic activity in kindled rats.

Power spectral analysis of the resting EEG activity of amygdala kindled rats revealed a decrease of power in the 1- to 3-Hz band and an increase in the 4- to 6-Hz band compared with 3-Hz-stimulated and operated control animals. This effect was observed only in the stimulated but not the contralateral amygdala. The alteration in power seen shortly after kindling was still evident after a 1-month stimulation-free period.

Amygdala↗

Status epilepticus following stimulation of a kindled hippocampal focus in intact and commissurotomized rats.

Status epilepticus of either a nonconvulsive, partial, or generalized form was provoked in rats by 60 min of electrical stimulation of a kindled focus in the posterior-ventral hippocampus. Following spontaneous offset of the nonconvulsive status epilepticus, minor pathology occurred which was largely restricted to the hippocampus, whereas partial or generalized status epilepticus produced considerable bilateral damage in the hippocampus, basolateral amygdala, and pyriform cortex. Bisection of the anterior half of the corpus callosum lateralized the forelimb motor seizures and bisection of the hippocampal commissure lateralized the hippocampal afterdischarge and the associated brain pathology. Paradoxically, commissurotomy also increased the probability of developing status epilepticus while reducing its severity. Further, it was shown that the right hippocampus precipitated status epilepticus with a higher probability than the left hippocampus in both intact and split-brain rats.

Action Potentials↗

Cellular and synaptic properties of amygdala-kindled pyriform cortex in vitro.

The evoked and spontaneous activity of neurons in the pyriform cortex of control and kindled rats was examined using a coronal slice preparation containing the amygdala-pyriform region. Electrical stimulation of the amygdala nuclei elicited synchronized burst responses in pyriform cells of slices from both control and kindled animals. The mean duration of the burst was greatly prolonged in cells from kindled preparations. The depolarizing synaptic events underlying the burst response in the kindled and control animals could be examined when Mg2+ was increased to suppress but not block synaptic transmission. Electrical stimulation evoked a short-latency graded synaptic depolarization, followed by a long-latency all-or-none depolarizing event, which appeared to be involved in generating the burst response. Norepinephrine (NE), in a 4-microM concentration, reversibly blocked the burst responses in the control preparation. Burst responses elicited from kindled preparations were also suppressed by NE. For the latter cases, higher concentrations of NE were required to produce this effect. The alpha-2-agonist clonidine mimicked the suppressive action of NE on the evoked events. In contrast the beta-agonist isoproterenol facilitated the occurrence of spontaneous synchronous bursts and prolonged evoked burst discharges in both the control and kindled preparations. NE and clonidine block the burst response by suppressing the underlying synaptic events. The facilitatory action of isoproterenol on spontaneous and evoked responses suggests that NE may also exert an excitatory effect.

Amygdala↗

Supersensitivity to the anticonvulsant and proconvulsant activity of clonidine following noradrenaline depletion induced by 6-hydroxydopamine.

Electrically induced focal cortical seizures were examined in 6-hydroxydopamine (6-OHDA) pretreated or control rats in the presence of 0, 1, 2.5, 5, and 10 micrograms/kg clonidine. In baseline determinations, rats pretreated with 6-OHDA showed lower seizure thresholds and longer behavioral and electrographic seizure than controls. Consistent with other reports, the lowest dose of clonidine (1 microgram/kg) inhibited seizures in control animals; 6-OHDA potentiated the anticonvulsant effect of the lowest dose of clonidine but exacerbated seizure in the presence of the highest dose of clonidine (10 micrograms/kg). Since others have reported proconvulsant effects of clonidine at much higher doses (100 or 1,000 micrograms/kg) using control animals, the depletion of forebrain norepinephrine with 6-OHDA therefore appears to produce a supersensitivity both to the proconvulsant and to the anticonvulsant effect of clonidine. These data suggest that the receptors that mediate the proconvulsant (possibly alpha 1 adrenoceptors) and the anticonvulsant (possibly alpha 2 adrenoceptors) effects are located postsynaptically.

Animals↗

Modification of local neuronal interactions by amygdala kindling examined in vitro.

Stimulation of the amygdala in coronal slices of the amygdala-pyriform region elicited burst responses in the pyriform cortex cells. The burst responses, recorded intracellularly, consisted of a train of action potentials riding on a depolarizing envelope that lasted for an average of 0.4 s. When a similar stimulus was applied to slices prepared from rats previously subjected to amygdala kindling, burst responses were significantly prolonged (average of 6.6 s). Our results indicate that the increased excitability of the chronic epileptic site developed in vivo was retained in the excised amygdala-pyriform slice.

Amygdala↗

Dorsal hippocampal kindling and transfer in split-brain rats.

The rate of kindling of a primary site in the dorsal hippocampus of rats was not altered by various forebrain commissurotomies or midbrain bisection. The positive transfer in the kindling of a secondary site in the homotopic hippocampus, on the other hand, was abolished by extensive forebrain transection, whereas anterior callosal or midbrain bisection alone was ineffective. In addition, there was no evidence of an interference effect when rekindling the original primary site. These results have important implications for interhemispheric mechanisms in kindling.

Animals↗

State-dependent learning following electrical stimulation of the hippocampus: intact and split-brain rats.

In experiment 1, electrical stimulation of the posterior hippocampus was shown to produce state-dependent learning (SDL) for a step-out inhibitory avoidance task in rats. Stimulation sites in either the right or left hippocampus were equally effective in producing this effect. Similarly, the presence or absence of afterdischarge (AD) following the stimulation did not differentially affect performance on the task. In experiment 2, forebrain bisection ameliorated the behavioral deficits in the animals receiving stimulation before testing but not before training (N/S group), while those stimulated before training but not before testing (S/N group) remained impaired; thus, providing a demonstration of asymmetrical SDL. Variations in extent of the commissurotomy differentially affected the laterality of the afterdischarge but not the performance in the SDL task. Speculation as to the mechanisms of this SDL effect was presented.

Animals↗

Lateralized state-dependent learning produced by hippocampal kindled convulsions: effect of split-brain.

In previous experiments, it was demonstrated that convulsions kindled from a ventral hippocampal focus in rats supported state-dependent learning which tended to lateralized to, and asymmetrical in, the right hemisphere. The question of the differential contribution of the left and right hippocampus to the production of state-dependency can best be addressed through confining the seizure to one or the other hemisphere via commissurotomy. In the present investigation, then, commissurally-intact and split-brain rats were implanted with bilateral hippocampal electrodes, then a left or a right focus was kindled. Later behavioral testing in an aversive inhibitory avoidance (IA) paradigm, revealed that intact animals, both left and right kindled groups, displayed good state-dependency. Split-brain animals, however, exhibited differential state-dependent responses to convulsive stimulation. Those kindled in the left hippocampus showed good retention when the conditions of seizure during training and testing were the same (same-state conditions), while showing deficient recall in changed-state conditions (a good state-dependent profile). On the other hand, those kindled in the right hippocampus displayed good retention of the IA experience in both same- and changed-state conditions. Differential recall after a left versus a right hippocampal convulsion in split-brain animals could not be accounted for in terms of differential seizure parameters, laterality of afterdischarge, extent of extracommissural damage or the extent of the actual transection. Possible mechanisms underlying this effect were discussed.

Animals↗

Long-term reduction in beta-adrenergic receptor binding after amygdala kindling in rats.

The long-term effect of amygdala kindling on beta-adrenergic receptor binding was examined in three groups of Wistar rats. The animals in one of two kindled groups received six stage-5 generalized convulsions, one each day, and then were not stimulated for 23 days before being killed (23-day group). Animals in the other kindled group received only five generalized convulsions prior to 22 days of no stimulation but then received their sixth convulsion 1 day before being killed (1-day group). All animals including the operated controls experienced similar handling. A significant reduction in [3H]dihydroalprenolol binding in the anterior cortex and kindled amygdala was observed in the 23-day animals compared with control animals, whereas the 1-day animals exhibited intermediate values which were not different from either of the other two groups. Thus, amygdala kindling results in a long-lasting reduction in beta-adrenergic binding which, paradoxically, can be partially ameliorated by a single convulsion 1 day before killing.

Amygdala↗

Relation between social rank, submissive behavior, and brain catecholamine levels in ring-necked pheasants (Phasianus colchicus).

In Experiment 1, the social hierarchy of 23 male ring-necked pheasants (Phasianus colchicus) was found to be linear except for positions in the middle ranks. Social rank was inversely correlated with submissive ("supercedent") behavior but was unrelated to size (weight) of the birds. In Experiment 2, with 8 cock pheasants, general activity of the birds was not correlated with social rank or supercedent behavior. These data suggest that the spatial displacement of one individual by another is not a random or neutral social process, or a function of size differences among birds. The catecholamine concentrations in several brain structures were determined. Only dopamine concentrations in the neostriatum of high-ranking males were reliably different (higher) from concentrations of low-ranking males. These concentrations were inversely correlated with supercedent behavior. These findings are discussed in terms of other pharmacological, neuroanatomical, and behavioral data.

Animals↗

A new model of partial status epilepticus based on kindling.

In this experiment, a new model of partial status epilepticus (SE) is described which is based on the antecedent development of a kindled focus. Following kindling, the amygdala was stimulated continuously for 60 min with the previous kindling stimulus (60 Hz sine wave, 50 microA peak-to-peak). This treatment provoked SE in 22 of 35 rats. Without drug intervention, rats spontaneously recovered (SR group) from the seizure between 10 and 24 h. After recovery from SE, after discharge (AD) thresholds were elevated and remained so for the 2 weeks before sacrifice. The histologies of these SR rats indicated massive gliosis and degeneration of the ipsilateral hemisphere, extending from the medial olfactory bulb, through the amygdala-pyriform cortex to the ventral hippocampus. Damage was observed frequently in the midline thalamic nuclei and hippocampal CA1 fields. Interruption of the SE with Nembutal 30 min after the stimulation offset (30 Min group) was occasionally associated with slight gliosis at the kindled electrode, whereas interruption after 4 h of SE (4 Hr group) resulted in more extensive cell loss. The AD thresholds of the 30 Min group, like those of the rats which did not develop SE (NSE group), returned to near-normal values by 2 weeks after SE; only the NSE rats exhibited generalized seizures to their AD threshold stimulus. This model of SE results in brain pathology similar to that found in other models, but has the advantage of being uncontaminated by exogenous chemicals and toxins.

Amygdala↗