John Gaito’s research while affiliated with University of Waterloo and other places

Eighteen experiments pairing the transfer experiment with the kindling paradigm were conducted. The brain homogenate supernatant from rats kindled to clonic convulsions was injected intraperitoneally into naive recipients. Similar material from nonkindled rats was injected into other naive recipients. One, two, two and one-half, and three brain amounts were used. Recipients receiving supernatant from kindled animals were retarded significantly in the development of clonic convulsions for all brain amounts. No clear retardation effect was obtained if the supernatant was injected intracerebrally or if the recipients had reached the convulsion stage.

Four experiments showed consistent differences in neurochemical measures between learning and nonlearning animals in the medial ventral cortex.

Data from a number of kindling experiments involving 60 convulsion trials were evaluated by a truncated principal components factor analysis to determine the number of common factors present. These data were obtained on 123 rats in which periodic low-intensity unilateral stimulation was alternated from one amygdala to the other after six convulsions on each side. Two dependent variables (latency of convulsion, duration of convulsion) were analyzed over Trials 1–60, 1–24, 25–60, 1–12, 13–24, 25–36, 37–48, and 49–60 for each dependent variable. Two factors appeared for all latency analyses: primary site stimulation (first side stimulated), secondary site stimulation (second side stimulated). The factor resolution was not clear for the duration measure; two to four factors were suggested in the various analyses.

Experiments were conducted to evaluate the effect of 5-day and 14-day intertrial intervals of 1-Hz brain stimulation on kindling behavior induced by 60-Hz sine-wave stimulation. The effective threshold intensity (ETI) to elicit a kindled response with 60-Hz stimulation was determined on two separate occasions with 15 brain-stimulation trials between determinations. In Experiment 1, experimental rats were stimulated with 1-Hz sine waves before and after a 60-Hz brain-stimulation trial, with a 14-day interval between each stimulation session (Group 1- 60-1). A second group (Group X-60-X) received only the 60-Hz stimulation on the same trials as those on which Group 1-60-1 was stimulated with 60-Hz current. Experiment 2 was similar to Experiment 1, but the interval was 5 days. In previous experiments with 1, 3, or 24 h between trials, Group 1-60-1 had had a gradual increase in the intensity required to elicit a kindled response with 60-Hz current from ETI1 to ETI4 (the suppression effect). However, with a 72-h interval, a decline similar to that of Group X-60-X occurred in ETI values. The results with 14-day and 5-day intervals were similar to those with a 72-h interval. Suppression of kindled behavior on daily trials was not present in Group 1-60-1, in contrast to the results with 1, 3, and 24 h. Apparently, intervals of 3 days or greater allow much of the suppression effect to dissipate.

Previous research indicated that an oscillation effect resulted during sequential alternation of unilateral amygdaloid stimulation with consistently low latency values for one side and consistently high values for the contralateral one when 30 sec was the duration of stimulation. In the present experiment, stimulation was for 5 sec. The oscillation tendency was the same with 5 sec duration as it had been with 30 sec.

Three experiments were conducted to evaluate the effect of 1-Hz brain stimulation of the amygdala on kindling behavior induced by 60-Hz sine-wave stimulation in the contralateral amygdala. In Experiment 1, the effective threshold intensity (ETI) to elicit a kindled response with 60-Hz stimulation was determined on four separate occasions with 15 trials between determinations (three per day) for each of three groups. Experimental rats in Group 1 were stimulated with 1-Hz sine waves in one amygdala, then with 60-Hz current in the opposite amygdala, followed by 1-Hz stimulation of the first site (1-60-1, OA), with 1-h interstimulation intervals. Group 2 was treated with the 1-60-1 pattern, but with all stimulation in the same amygdala (1-60-1, SA). Group 3 received only the 60-Hz stimulation trials (X-60-X), on the second trial. Group 2 showed the typical suppression result, a gradual increase in threshold over the four ETI determinations. However, Group 1’s responses were similar to those of Group 3: ETI values decreased gradually over the determinations. Later, when Group 1 received a set of trials in which 1- and 60-Hz current stimulation was to the same site, suppression responses occurred. Two further experiments were conducted with similar results. These results suggest that the suppression effect generated by 1-Hz stimulation appears to involve a local process, an intrahemispheric effect.

Five experiments were conducted in which donor rats were kindled to the clonic-convulsion stage, sacrificed, and their brains removed. The brain was homogenized, and the supernatant fraction was injected intraperitoneally into recipient experimental rats, who then were subjected to the kindling procedure. Control donors which received no stimulation were included. When the injection involved two or more brain amounts, a retarding effect tended to occur with the experimentals. If only one brain amount was used for the injection, no change resulted in the kindling rate of these recipients. This interanimal negative-transfer effect appears to be similar to the intraanimal negative-transfer effect reported by Mclntyre and Goddard.

Previous experiments indicated that the development of clonic convulsions could be retarded by intraperitoneal injections of brain homogenate supernatant from male Wistar rats which had convulsed via amygdaloid electrical stimulation if two or more brain equivalents were used. Six experiments were conducted employing intracerebral injections. Although significant differences appeared in one experiment, the overall effect was one of no difference between experimental (E) and control (C) recipients. However, the mean number of trials for first clonic convulsion was greater for E and C than for E donors, and for recipients in the previous intraperitoneal experiments, suggesting possible disruption of brain function with this type of injection. Thus, two further experiments were conducted with male Wistar rats using the intraperitoneal route of injection and separating the homogenate into two fractions: molecular weight less than 500, molecular weight greater than 500. In the fraction greater than 500 molecular weight, E mean value to first clonic convulsion was greater than that for C, confirming results of the previous experiments.

In two experiments, rats were subjected to a sequence of electrical stimulations alternating from one amygdala to the contralateral one. Each phase of stimulation was for six convulsions prior to alternation to the other side. An oscillation effect resulted, involving low trials to six clonic convulsions and low latency to convulse for stimulation of one side, but high values of these measures for the contralateral site. The oscillation persisted, especially for the latency measure, even when one phase of bilateral stimulation preceded unilateral stimulation, when a 17- to 23-day rest period was inserted following a sequence of alternations and when two phases of bilateral stimulation occurred following postrest unilateral stimulations. The oscillation effect was less prominent in the number of trials to six convulsions data and almost nonexistent in duration of convulsion. Of 16 rats used in 15 to 19 alternating phases, 7 oscillated throughout all of these phases in latency data, but none showed oscillation over all phases in the other dependent variables.

Data from a number of sequential alternation experiments were factor analyzed to determine the number of common factors present. Three dependent variables (latency of convulsion, number of trials to six convulsions, duration of convulsions) were evaluated by three procedures: principal components solution with 1s in main diagonals, principal axes solution with largest r in the diagonals, principal axes solution with R2 in the diagonals. The results were similar; the presence of two factors was suggested in the latency and criterion measures (primary site stimulation and secondary site stimulation) and one in the duration data. A principal components factor analysis over the three dependent variables showed the presence of three factors, those observed in each of the separate analyses.