Conditioning of a flavor aversion in rats by amygdala kindling

Rats received 30 stimulations and 30 sham stimulations (the lead was attached to the subjects but no current was delivered) to the left basolateral amygdala in a quasirandom sequence. Stimulations were preceded by the presentation of 1 flavored solution conditional stimulus (CS+); sham stimulations were preceded by the presentation of another flavored solution, CS-. As kindled motor seizures developed, the rats began to consume significantly less of the CS+ than the CS-. Moreover, at the end of the experiment, the rats consumed significantly less of the CS+ than the CS- during a 20-min conditioned flavor preference test in which both solutions were available simultaneously. These findings confirm and extend the recent report that interictal changes in defensive behavior can be conditioned by amygdalar kindling.     

Extinction deficit and fear reinstatement after electrical stimulation of the amygdala: implications for kindling-associated fear and anxiety

Generalized seizures produced by electrical kindling of the amygdala in laboratory rats are a widely used animal model of temporal lobe epilepsy. In addition to seizure evolution amygdala kindling enhances emotionality. The relative roles of electrical stimulation and seizure induction in fear responding are unclear. Here we investigate this issue using extinction and reinstatement of fear-potentiated startle. After classical conditioning (light+footshock pairings) laboratory rats were fear extinguished with each light presentation followed by nonepileptogenic amygdala stimulation. In contrast to the normal extinction learning of control subjects, amygdala stimulated animals exhibited conditioned fear after 120 presentations of the nonreinforced conditioned stimulus (CS). In a second experiment electrical stimulation of the amygdala restored extinguished fear responding and the fear reinstatement was specific to extinction context. The reinstatement effect did not involve sensitized fear to the CS produced by amygdala stimulation. The possibility that electrical activation of the amygdala produces unconditioned fear was considered. Animals uniformly failed to demonstrate fear-potentiated startle using electrical stimulation of the amygdala as the unconditioned stimulus. This was the case with a subthreshold afterdischarge stimulus and a stimulation schedule that produced kindled seizures. The extinction deficit and fear reinstatement results were interpreted to suggest that amygdala stimulation activates acquired excitatory stimulus-affect neural connections formed during Pavlovian fear conditioning. Our data supports a model in which excitation of an amygdala-based memory-retrieval system reinforces the expression of learned fear behaviors.     

Flavor preferences conditioned by postingestive effects of nutrients in preweanling rats

The purpose of these experiments was to determine if preweanling rats, like adults, are capable of learning to associate an arbitrary flavor with the postingestive effects of nutrients, and then demonstrate a preference for that flavor after weaning. In Experiment 1, preweanlings were trained daily from postnatal day (P) 16 through P19 with intraoral (IO) infusions of a grape or cherry flavor (CS+) mixed with 20% glucose (US), and the opposite flavor (CS-) mixed with 0.05% saccharin. After weaning, rats were given a 4-h two-bottle choice between the CS+ and CS- flavors both presented in 0.05% saccharin. Rats preferred the flavor previously paired with glucose. In Experiment 2 using similar methods, rats learned to prefer a flavor (CS+G) paired with a glucose US over a flavor (CS+S) paired with a sweeter but less nutritive sucrose US, indicating involvement of postingestive reinforcement. In Experiment 3 preweanling rats with IO and intragastric (IG) catheters were trained with a CS+ flavor paired with IG nutrient infusion, and a CS- flavor paired with no IG infusion. These rats showed no flavor preference 3 days after weaning, but did significantly prefer the CS+ flavor over the CS- flavor 10 days after weaning. Together these experiments demonstrate that neural mechanisms for flavor-nutrient associations are developed before weaning, allowing young rats to learn associations between arbitrary flavors and nutritive consequences. Thus nutrient conditioning may be one way that early experience (such as flavors from the maternal diet transmitted in milk) influences later dietary preferences.     

Ethanol-conditioned flavor preferences compared with sugar- and fat-conditioned preferences in rats

Rats can learn to prefer flavors paired with ethanol and various nutrients. The present study examined the relative strengths of flavor preferences conditioned by 5% ethanol and isocaloric solutions of 7.18% sucrose, 7.18% fructose, or 3.26% corn oil. In three experiments, nondeprived rats were trained with different flavored solutions (conditioned stimuli, CS) paired with intragastric (IG) infusions: a CS+E flavor paired with ethanol infusion, a second CS+ paired with a nutrient infusion, and a CS- paired with water infusion. In two-bottle tests, rats strongly preferred a sucrose-paired CS+S over the CS- and over the CS+E. The preference for the CS+E over CS- was weaker. These effects occurred when the rats drank substantially more CS+S than CS+E in training and when training intakes were matched. Similar results were obtained when the nutrient infusion was fructose or corn oil, except that preferences for the CS+F or CS+O over the CS+E were less pronounced than with CS+S. Consistent with the IG results, rats trained to drink flavored sucrose and ethanol solutions preferred the CS+S to CS+E in a flavored water test. These results confirm prior reports of ethanol-conditioned preferences but show that ethanol is less effective than other nutrients at isocaloric concentrations. The marked individual differences in ethanol-conditioned preferences may be related to the impact of the sugar or fat infusions on the reward evaluation of the ethanol-paired flavor.     

Prevention of amygdala kindling with an inhibitor of gamma-aminobutyric acid uptake

A novel, specific inhibitor of gamma-aminobutyric acid (GABA) uptake, SKF 89976-A (N-[4,4-diphenyl-3-butenyl]-nipecotic acid), was administered daily (15 mg/kg, i.p.) 30 min prior to amygdala stimulation in adult female rats. Whereas control rats developed full kindled seizures after 9.4 +/- 1.2 amygdala stimulations. SKF 89976-A-treated rats had not progressed beyond an early stage of kindled seizures by the termination of drug treatment after 22 episodes of daily amygdala stimulation. Following cessation of SKF 89976-A treatment, full kindled seizures developed after 4.1 +/- 0.9 additional amygdala stimuli. The data suggest that SKF 89976-A can inhibit generalization of amygdala-kindled seizures, possibly by enhancement of central GABAergic activity.     

Anticipating the attack: temporal conditioning during amygdala kindling in rats

The present study showed that amygdala-kindled rats use short-interval timing superimposed on phase or ordinal timing to predict when a convulsion will occur. In 2 experiments, rats received 1 stimulation and 1 sham stimulation each day, always at the same times (conditioned stimulus [CS]+ and CS- times, respectively) and 150 s after rats had been placed in the testing chamber (the preadministration interval). As kindling progressed, the rats displayed more defensive behavior at the CS+ time than at the CS- time. Then, a stimulation-free peak-procedure test was conducted: At the CS+ time, but not at the CS- time, defensive behavior increased progressively as the 150-s preadministration interval elapsed, and then it gradually declined.     

Flavor preferences conditioned by intragastric fructose and glucose: differences in reinforcement potency

Many prior conditioning studies indicate that fructose, unlike glucose, has minimal postingestive reinforcing effects. Using a new training procedure, food-restricted rats were trained in alternate 20-h/day sessions with one flavored solution (CS+F) paired with intragastric (IG) infusions of 16% fructose and another flavor (CS-) paired with IG water. In subsequent two-bottle tests they showed a robust (85%) preference for the CS+F over the CS-. A third flavor (CS+G) was then paired with IG 16% glucose, and it was strongly preferred to the CS+F. When retrained 30 min/day with new flavors paired with IG fructose, glucose, or water the rats learned only a CS+G preference. When training was extended to 20 h/day, a CS+F preference developed. New rats trained 20 h/day with two-bottle access to CS+F and CS- paired with IG fructose and water failed to acquire a CS+F preference. Other rats rapidly developed a strong preference when trained with concurrent access to CS+G and CS- paired with IG glucose and water. These data indicate that both fructose and glucose generate postingestive reinforcing signals, but that the fructose signals are weaker and/or delayed relative to those produced by glucose.     

Conditioned flavor avoidance, preference, and indifference produced by intragastric infusions of galactose, glucose, and fructose in rats.

The postingestive reinforcing and satiating effects of intragastric (i.g.) infusions of 16% galactose, glucose, and fructose were compared in adult female rats. In Experiment 1, food-restricted rats were trained to drink (30 min/day) flavored solutions (the CS+Gal and CS+Glu) paired with intragastric (i.g.) infusions of galactose and glucose; other flavors (the CS-) were paired with IG water infusions. In subsequent choice tests, the rats strongly preferred (91%) the CS+Glu to the CS-, but avoided the CS+Gal (21%) in favor of the CS-. In Experiment 2, the rats were trained with a CS+Fru paired with i.g. fructose infusions and a CS- paired with i.g. water. In the choice test they consumed similar amounts of CS+Fru and CS- (CS+Fru preference = 51%). In other choice tests they preferred the CS+Glu (>80%) to CS+Fru and CS+Gal, and the CS+Fru (81%) to CS+Gal. Satiation tests were performed in Experiment 3 by adapting the rats to drink a 3% sugar + 0.2% saccharin solution paired with i.g. water infusions (30 min/day). On different test days 16% sugar instead of water was infused. IG galactose, glucose, and fructose produced comparable reductions in sugar+saccharin intake in the first test session. These findings demonstrate that, while the three sugars had similar satiating effects, they differed substantially in their postingestive flavor conditioning effects. The glucose and fructose results confirm prior data indicating that only glucose generates potent postingestive reinforcing stimuli. The galactose-induced flavor avoidance indicates that this sugar has a negative postingestive consequence. This may be due to the slow and incomplete hepatic metabolism of this sugar in adult rats. Conceivably, galactose intolerance may contribute to the lactose avoidance in adult animals.     

Correlation between long latency evoked potentials from amygdala and evoked cardiac response to fear conditioned stimulus in rats

We investigated relation between activity of central nucleus of amygdala (CE) and phasic heart rate deceleration during differential fear conditioning. We found that P2 component of long-lasting event potential (EP) to CS+ but not to CS- correlated strongly with HR deceleration in the 1st second after stimulus onset. The obtained results are discussed in the light of LeDoux's and Kapp's findings showing crucial role of amygdala in processing of emotionally relevant stimulation and it's involvement in initiating autonomic responses.     

Flavor preference conditioning as a function of fat source

Rats learn to prefer foods based, in part, on postingestive nutrient actions. This study compared the effectiveness of intragastric (IG) infusions of fat emulsions which varied in their fatty acid composition (chain length and saturation) to condition preferences for flavored saccharin solutions. In Experiment 1, food-restricted rats were trained (30 min/day) with one flavor (CS+CO) paired with IG corn oil (CO) and a second flavor (CS+MCT) paired with IG medium chain triglyceride (MCT); the fats were prepared as isocaloric emulsions. A third flavor (CS-) was paired with IG water. The rats subsequently showed a strong preference for the CS+CO (84%) and a weaker preference for the CS+MCT (65%) relative to the CS-. In a direct choice test, the CS+CO was preferred to the CS+MCT by 75%. In Experiment 2, new rats trained with flavors paired with IG corn oil and beef tallow (BT) infusions learned to prefer both the CS+CO (89%) and the CS+BT (82%) relative to the CS-, and preferred the CS+CO to the CS+BT by 67%. The same rats were trained with three new flavors paired with IG infusions of corn oil, vegetable shortening (VS), and water. The rats strongly preferred both the CS+CO (91%) and CS+VS (86%) over the CS-, and they preferred the CS+CO to the CS+VS by 64%. In Experiment 3, new rats trained with corn oil and safflower oil (SO) paired flavors preferred both the CS+CO and CS+SO to the CS-, and equally preferred the CS+CO and CS+SO in two-bottle tests. The rats were also given one-and two-bottle tests with the various fat emulsions and their preference profile was consistent with their conditioned preferences for the flavored saccharin solutions. These findings demonstrate that many different fat sources can condition flavor preferences. Fats with high polyunsaturated content and/or lower saturated fat content are the most reinforcing.     

Hemodynamic responses of the amygdala, the orbitofrontal cortex and the visual cortex during a fear conditioning paradigm.

Functional magnetic resonance imaging (fMRI) studies consistently demonstrate an enhanced activation of the visual cortex in reaction to emotionally salient visual stimuli. This increase of activation is probably modulated by top-down processes, that are initiated in emotion processing structures, specifically the amygdala and the orbitofrontal cortex. In the present fMRI study, a differential fear conditioning paradigm was applied to investigate this assumed modulation. Hemodynamic responses towards a neutral visual stimulus (CS+) predicting an electrical stimulation (UCS) were compared with responses towards a neutral and unpaired stimulus (CS-). Thereby, particularly the time courses of neural responses were considered. Skin conductance measures were concurrently recorded. Our results show that the differentiation between CS+ and CS- within the amygdala and the extended visual cortex was accomplished during a late acquisition phase. In the orbitofrontal cortex the differentiation occurred at an earlier stage and was then sustained throughout acquisition. It is suggested that these altering activation patterns are reflecting different phases of learning, integrating the analyzed regions to varying degrees. Additionally, the results indicate that statistical analyses comprising a temporal variation of hemodynamic responses are more likely to detect amygdala activation.     

Flavor preferences conditioned by high-fat versus high-carbohydrate diets vary as a function of session length.

Intragastric (i.g.) infusions of fat and carbohydrate condition flavor preferences in rats, but different results have been obtained in studies using pure and mixed nutrient infusions. This experiment compared the preference conditioning effects of mixed high-carbohydrate (HC) and high-fat (HF) diet infusions during short-term and long-term sessions. In Experiment 1 food-deprived rats were given one flavored saccharin solution (CS+HC) paired with i.g. infusions of an HC liquid diet, a second flavor (CS+HF) paired with HF diet infusions, and a third flavor (CS-) paired with i.g. water infusions during 30-min one-bottle training sessions. In subsequent two-bottle tests (30 min/day), the rats preferred both CS+s to the CS- and preferred the CS+HC to the CS+HF. In Experiment 2, the same rats were trained and tested with the CSs and paired infusions during 22 h/day sessions with chow available ad lib. Both CS+s were again preferred to the CS-, but now the CS+HF was preferred to the CS+HC. When given additional 30-min choice sessions in Experiment 3 the rats showed no reliable preference for the CS+HC versus CS+HF under food-deprived or ad lib conditions. In Experiment 4, the rats were given 22-h CS+HC versus CS+HF choice sessions every other day. They showed no reliable CS preference during the first 30 min of each session, but reliably preferred the CS+HF during the remaining 21.5 h. These findings indicate that previously reported differences in preferences conditioned by pure versus mixed nutrient infusions are due to training procedures (session length, deprivation state) rather than to the type of nutrient infusions per se. The rats displayed different CS+HF versus CS+HC preferences as a function of test duration even after being given both short- and long-term training. Thus, short-term choice tests do not always predict the long-term intakes and preferences for high-fat and high-carbohydrate foods.     

Acquisition and retention of separate elements of a conditioned olfactory discrimination in preweanling rats

Acquisition and retention of separate elements of an olfactory discrimination were tested in 15- and 20-day-old preweanling rats. Four or 8 conditioning trials were given in Experiment 1. Each rat was presented one odor always followed by footshock (CS+) and another never paired with footshock (CS-). Conditioning to both stimuli was assessed through 3 types of olfactory preference tests involving comparison between CS+ and a novel odor, CS- and a novel odor, or CS+ and CS-. The results indicated that for 15- and 20-day-olds, both stimuli become excitatory early in training; further conditioning trials diminished the excitation previously accrued to the CS-, and the olfactory discrimination became apparent. When levels of conditioning were equated, retention was tested after intervals of 4 min, 3 days, or 8 days (Exp. 2). Rate of forgetting was more rapid for the 15-day-olds, but both ages of subjects showed similar patterns of forgetting, which included a progressive decrease in the aversion to the CS+ but an increase in aversion to the CS-.     

Selective expression of electrical correlates of differential appetitive classical conditioning in a feeding network

Electrical correlates of differential appetitive classical conditioning were recorded in the neural network that underlies feeding in the snail Lymnaea stagnalis. In spaced training (15 trials over 3 days), the lips and the tentacle were used as CS+ (reinforced conditioned stimulus) or CS- (nonreinforced conditioned stimulus) sites for behavioral tactile conditioning. In one group of experimental animals, touch to the lips (the CS+ site) was followed by sucrose (the unconditioned stimulus, US), but touch to the tentacle (the CS- site) was not reinforced. In a second experimental group the CS+/CS- sites were reversed. Semi-intact lip-tentacle-CNS preparations were made from both experimental groups and a naive control group. Intracellular recordings were made from the B3 motor neuron of the feeding network, which allowed the monitoring of activity in the feeding central pattern generator (CPG) interneurons as well as early synaptic inputs evoked by the touch stimulus. Following successful behavioral conditioning, the touch stimulus evoked CPG-driven fictive feeding activity at the CS+ but not the CS- sites in both experimental groups. Naive snails/preparations showed no touch responses. A weak asymmetrical stimulus generalization of conditioned feeding was not retained at the electrophysiological level. An early excitatory postsynaptic potential (EPSP) response to touch was only enhanced following conditioning in the Lip CS+/tentacle CS- group but not in the Tentacle CS+/lip CS- group. The results show that the main features of differential appetitive classical conditioning can be recorded at the electrophysiological level, but some characteristics of the conditioned response are selectively expressed in the reduced preparation.     

Differential reinforcing and satiating effects of intragastric fat and carbohydrate infusions in rats.

Food intake and preferences are modulated by the postingestive satiating and reinforcing actions of nutrients. This experiment compared the feeding effects of isocaloric intragastric (i.g.) carbohydrate (maltodextrin) and fat (corn oil) infusions in food-restricted rats fed low-fat (12% fat kcal) or high-fat (48% fat kcal) diets. In Experiment 1, the rats were given one flavored saccharin solution (CS+C) paired with i.g. carbohydrate infusions, a second flavor (CS+F) paired with i.g. fat infusions, and a third flavor (CS-) paired with i.g. water infusions during 30-min one-bottle training sessions. In subsequent two-bottle tests, the rats preferred both CS+s to the CS- (68-83%) and the CS+C to the CS+F (68-70%). In Experiment 2, the feeding inhibitory effects of the nutrient infusions on an ongoing meal (satiation test) or a subsequent meal (satiety test) were compared. The intake of a palatable Polycose+saccharin solution was suppressed by a concurrent carbohydrate infusion but not by a fat infusion. Also, i.g. carbohydrate preloads suppressed the intake of a subsequent (30-180 min) mixed carbohydrate+fat test meal more than did i.g. fat preloads. The satiety effects of the fat preloads were more pronounced in rats fed the low-fat diet than in rats fed the high-fat maintenance diet. Diet composition did not reliably influence the preference conditioning and satiation effects of the nutrient infusions. These results confirm prior reports that fat is less satiating than carbohydrate, and further demonstrate that i.g. carbohydrate infusions condition a stronger flavor preference than fat infusions.     

Low-frequency stimulation reverses kindling-induced neocortical motor map expansion

Repeated application of low-frequency stimulation can interrupt the development and progression of seizures. Low-frequency stimulation applied to the corpus callosum can also induce long-term depression in the neocortex of awake freely moving rats as well as reduce the size of neocortical movement representations (motor maps). We have previously shown that seizures induced through electrical stimulation of the corpus callosum, amygdala or hippocampus can expand the topographical expression of neocortical motor maps. The purpose of the present study was to determine if low-frequency stimulation administered to the corpus callosum could reverse the expansion of neocortical motor maps induced by seizures propagating from the hippocampus. Adult Long-Evans hooded rats were electrically stimulated in the right ventral hippocampus, twice daily until 30 neocortical seizures were recorded. Subsequently, low-frequency stimulation was administered to the corpus callosum once daily for 20 sessions. High-resolution intracortical microstimulation was then utilized to derive forelimb-movement representations in the left (un-implanted) sensorimotor neocortex. Our results show that hippocampal seizures result in expanded motor maps and that subsequent low-frequency application can reduce the size of the expanded motor maps. Low-frequency stimulation may be an effective treatment for reversing seizure-induced reorganization of brain function.     

Energy density and macronutrient composition determine flavor preference conditioned by intragastric infusions of mixed diets

In prior studies rats preferred a flavor (CS+HF) paired with intragastric (IG) infusions of a high-fat diet to a flavor (CS+HC) paired with a high-carbohydrate diet, yet just the opposite preference was observed with pure-nutrient infusions. The present study tested the hypothesis that variations in nutrient density as well as composition influence flavor learning. Animals were trained (22 h/day) with IG infusion of milk-based high-fat and high-carbohydrate liquid diets paired with intakes of flavored, noncaloric CS+ solutions. A third flavor, the CS-, was paired with water infusion. Standard chow was available ad libitum. The rats preferred both CS+ flavors to the CS-, whether the infused diets were dense (HF and HC, 2.1 kcal/ml) or dilute (hf and hc, 0.5 kcal/ml), indicating that all diet infusions were reinforcing. They consumed the CS+hc and CS+hf equally in training, and preferred the CS+hc, showing that at low-energy density carbohydrate was more reinforcing than fat. In contrast, CS+HF intake exceeded that of CS+HC in training, and the rats preferred the CS+HF to the CS+HC. In further tests the rats preferred the CS+HF to the CS+hc, the CS+HF to the CS+hf, and the CS+HC to the CS+hc; i.e., when the diets differed in energy density the flavors associated with the more concentrated infusions were preferred. In the absence of influence by flavor cues from the nutrients themselves, rats' preferences for flavors associated with diets high in fat or carbohydrate are dependent on energy density. The differential satiating effects of fat and carbohydrate may contribute to these density-dependent preferences.     

Amygdaloid kindled seizures induce weight gain that reflects left hemisphere dominance in rats

The present study sought to determine the effects of kindled seizures generated from the left and right amygdala upon weight gain in rat. Seventy-five female Sprague-Dawley rats were implanted with electrodes in basal amygdala of the left and right hemispheres. A kindling paradigm was employed in which electrical stimulation was applied once per day for 30 days after Stage 5 seizures. An electrode was implanted into the basal amygdala of the control rats but no stimulation was applied. All rats were weighed daily during the course of the experiment and changes in weight during this period were recorded for all rats. The results demonstrated that kindling from either the left or right amygdala induced significant increases in weight gain relative to the control rats. However, kindling from the left basal amygdala induced increases in body weight that were four times greater than control rats and two times greater than the rats kindled from the right side of the basal amygdala. Likewise, serum leptin levels, which were highly correlated with weight gain, also showed significantly greater increases in left amygdaloid kindled rats relative to rats kindled from the right amygdala and control rats. These findings demonstrate that basal amygdaloid kindling induces significant increases in weight gain and that the magnitude of these effects is linked to the dominance of the left hemisphere.     

Effects of selective excitotoxic lesions of the nucleus accumbens core,anterior cingulate cortex,and central nucleus of the amygdala on autoshaping performance in rats

The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an unpaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS+ significantly less often than controls, failing to discriminate between the CS+ and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations.     

Propagation of amygdala-kindled seizures to the hippocampus in the rat: electroencephalographic features and behavioural correlates

BACKGROUND: The propagation of amygdala-kindled seizures to the dorsal and ventral hippocampus was examined, in rats. The relation of contralateral seizure propagation to the onset of generalized convulsions was also studied. METHODS: In all subjects, electrodes were implanted in the amygdala. Two additional electrodes were implanted (bilaterally) in the dorsal (n = 6) or ventral (n = 8) hippocampus. Kindling stimulations were delivered twice daily (interval 4 h). RESULTS: Initially, triggered after-discharges (ADs) were recorded only in the amygdala. With repeated stimulation, the AD propagated to the hippocampus. Rates of propagation were as follows (mean # of stimulations +/- SEM): ipsilateral ventral hippocampus, 4.0 +/- 0.9; ipsilateral dorsal hippocampus, 6.2 +/- 1.4; contralateral dorsal hippocampus, 7.5 +/- 1.4; contralateral ventral hippocampus, 8.5 +/- 1.0. AD propagation to contralateral sites was significantly slower than to ipsilateral sites. Ipsilateral hippocampal recruitment occurred between stages 1 and 2 (partial seizures), whereas contralateral hippocampal recruitment occurred between stages 2 and 3 (transition to generalized seizures). SUMMARY: These results indicate that during amygdala-kindling, it takes several stimulations before discharge propagates to the hippocampus. The close link between contralateral hippocampus involvement and seizure generalization warrants further study, and may lead to a better understanding of the pathways involved in seizure spread.