The effect of novelty, an environmental background variable affecting feeding and appetitive learning performance, was examined in a behavioral study of the pond snail Lymnaea stagnalis. Transfer of snails into a novel aquatic environment (clean water) evoked exploratory behavior which manifested itself in an increased number of spontaneous rasping movements of the mouth over the second to fifth minute after exposure to the novel environment. The intensity of this behavior was much weaker in a familiar environment (used water from the home tank). Similarly, sucrose-induced feeding rates were highest when the snails were given the sucrose stimulus in a novel environment. The effectiveness of appetitive conditioning using tactile stimulus paired with food (Kemenes & Benjamin, 1989a) improved when the snails were subjected to conditioning in a novel environment. Satiety, an internal variable, suppressed the stimulating effects of the novel environment on the spontaneous, unconditioned, and conditioned feeding alike. After training in the novel environment, the conditioned response was retained for up to 12 days and thus provided a robust behavioral paradigm for the extension of the analysis to the neurophysiological mechanisms of factors affecting appetitive learning in molluscs.
The effect of 2-deoxygalactose (2-D-gal), an inhibitor of glycoprotein synthesis, on memory formation was investigated with the day-old chick trained on a single-trial passive discrimination task. 2-D-gal (10 mu mol/chick) was shown to inhibit memory formation at a time before the emergence of an antibiotic-sensitive long-term memory stage. The amnestic effect of 2-D-gal was successfully prevented by galactose, and more significantly by noradrenaline. In contrast, anisomycin-induced amnesia was resistant to challenge by either galactose or noradrenaline. The results are consistent with the view that some glycoprotein involvement in memory formation occurs prior to the formation of protein synthesis-dependent longterm memory, and this role of glycoproteins may be associated with the triggering of long-term memory formation by noradrenaline. (C) 1994 Academic Press, Inc.
Rats were bilaterally implanted with cannulae in the entorhinal cortex, amygdala, and hippocampus; after recovery, they were trained in a step-down inhibitory avoidance task and tested for retention 24 h later. Muscimol (0.03 microgram) or D-amino-5-phosphonovalerate (5.0 micrograms) infused in the entorhinal cortex 20 min prior to training inhibited the amnestic effect of the same dose of muscimol infused into this area 100 min after training. Thus, memory-relevant information must be processed by the entorhinal cortex at the time of training in order that this cortex may play a late post-training role in memory processing. Pretraining intraentorhinal muscimol administration did not affect the amnestic effect of the post-training infusion of muscimol into the amygdala and hippocampus, or the inhibition of memory expression induced by a pretest infusion of CNQX into the amygdala and hippocampus or into the entorhinal cortex. Pretest intraentorhinal muscimol also did not influence the effect of pretest intra-amygdala and intrahippocampal CNQX administration. These data indicate that the cells of the entorhinal cortex that are sensitive to pretraining muscimol are not part of the inputs that lead to post-training processing by the amygdala and hippocampus, or to the intervention of the amygdala, hippocampus, and entorhinal cortex in memory expression. The present findings are compatible with the possibility that, instead, the entorhinal cortex may be an output of the amygdala and hippocampus at the time of memory expression.
The present study employed the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to investigate the possible importance of NMDA receptor activation for naturally occurring spatial learning in birds by exploiting the navigational ability of homing pigeons (Columba livia). Control pigeons released from two unfamiliar release sites displayed vanishing bearings that were poorly oriented. However, when released a second time from the same sites they displayed improved homeward orientation. The control birds apparently learned something about the spatial relationships of stimuli at the release sites on the first releases and used that information to orient better when released a second time from the same locations. Experimental pigeons given the NMDA receptor antagonist MK-801 (0.10 mg/kg) initially behaved as controls, orienting poorly when released for the first time from the two sites. In contrast to controls, the experimental birds failed to show significant improvement in orientation when released again from the same sites without MK-801. A second experiment revealed no state-dependent learning. Results of a position/color discrimination task showed that the impairments observed did not generalize to associative learning in an operant chamber, and together with field observations were not a result of sensory or motor drug effects. The data indicate that blocking NMDA receptors can disrupt navigational learning in homing pigeons. As such, the results are consistent with the hypothesis that NMDA receptor activation plays an important role in spatial learning in birds.
Previous studies indicate that somatosensory inputs to the snout and the ventral trunk play critical roles in the elicitation and maintenance of maternal aggression by postpartum lactating Long-Evans Norway rats toward a strange male intruder. In the present studies we examined the possible influence of visual and auditory stimuli in the display of this behavior. In Experiment 1, dams temporarily deprived of visual or auditory input by eyelid suturing or ear molds, respectively, on Day 2 postpartum, were found to have normal levels of maternal aggression 1 day later. In Experiment 2, males were found to contribute about 50% of the short-duration 50-kHz vocalizations, which begin shortly after introduction of the intruder, and all of the long-duration 22-kHz vocalizations, which begin after the onset of attacks. Nonetheless, females tested with males surgically devocalized 7 days earlier were not significantly different in aggressiveness from dams tested with vocalizing males on either Day 1 or Day 4 postpartum. These findings indicate that visual or auditory inputs from the pups or intruder are not critical to the display of maternal aggression in rats, at least within the confines of laboratory housing.
This experiment investigated the effect on memory, in rats, of the bilateral intrahippocampal post-training infusion of two different inhibitors of protein kinase C activity, staurosporin and CGP41231. Male Wistar rats were implanted bilaterally with cannulae aimed at the CA1 region of the dorsal hippocampus. After recovery from surgery, they were trained in step-down inhibitory avoidance using a 0.5-mA footshock and tested for retention 24 h later. Immediately or 30, 120, or 180 min after training they received, through the cannulae, infusions of vehicle, staurosporin (1.0 mu g), or CGP41231 (2.5 mu 8) The two drugs caused full retrograde amnesia when given immediately or 30 min post-training, partial amnesia when given 120 min after training, and had no effect when given 180 min after training. The results support the suggestion that memory involves long-term potentiation initiated at the time of training in the hippocampus. Inhibitors of protein kinase C block the development of long-term potentiation when administered in the first 2 h after induction. (C) 1994 Academic Press, Inc.
Three experiments assessed the effects of beta-amyloid 1-40 (beta A4) on spatial learning in Sprague-Dawley rats. In Experiment 1, rats were trained on a signaled footshock avoidance in a Y-maze. Rats received a single injection of beta A4 or vehicle in both sides of the hippocampus immediately after the fifth trial. The beta A4 group took significantly longer than the vehicle group to learn to avoid the shock when trained to criterion I week later, suggesting a detrimental effect of beta A4 on memory consolidation. Experiment 2 used a food reinforcer rather than shock relief under procedures similar to Experiment 1. Again, the beta A4 group took longer to learn the maze to criterion. This shows that the effect in Experiment 1 was not specific to shock-maintained learning. In Experiment 3, rats were trained to retrieve a food pellet fi om each arm of an eight-arm radial maze. After training to criterion, beta A4 or vehicle was administered intrahippocampally 30 min before the daily session for 26 sessions. There were no acute or chronic effects of beta A4 injection on radial maze performance, and no aggregation of beta A4 or significant necrosis was observed upon postmortem histological analysis. These experiments suggest that single injections of beta A4 impair memory consolidation, but repeated injections of beta A4 over an extended period do not affect well-learned behavior. (C) 1994 Academic Press, Inc.
In the present investigation the functional activity of transport systems mediating the GABA and L-glutamate uptake into nerve terminals of the rat brain cortex and hippocampus in response to a single carbacholine administration to hippocampus was studied. It has been established that synaptosomes isolated from the brain cortex and hippocampus of rats used in the experiments 24 h after a single carbacholine injection possess an increased capability of GABA and L-glutamate accumulation, and 48 h later the GABA and L-glutamate uptake begins to return to its control level and was equal to it on seventh day after injection.
It was recently reported that administration of relatively high intensities of footshock (overreinforcement) during training of passive avoidance protected animals against the amnesic effect of scopolamine, injected 5 min after training. This was interpreted in terms of a lesser involvement of acetylcholine in memory consolidation. An alternative explanation was that overreinforcement accelerated the consolidation process, which could have taken place before the injection of scopolamine. To test for this possibility, male Wistar rats were injected with 4, 8, or 12 mg/kg of scopolamine, 5 min before training with low or high levels of footshock and then tested for retention of the task. Scopolamine induced the expected memory deficit after the low-intensity footshock; after overreinforcement the higher doses of scopolamine induced state dependency, while no deficits were produced with the lower dose. It was concluded that: (a) acetylcholine is indeed involved in memory consolidation of passive avoidance; (b) scopolamine interacts with high footshock levels to produce state dependency; and (c) when relatively low doses of scopolamine are used in conditions of overreinforcement, protection against scopolamine-induced amnesia becomes evident.
A role for the 5-HT1A receptor in learning and memory has been suggested by diverse evidence. The present paper deals with the acute effect of 8-OH-DPAT (a 5-HT1A agonist) administered to rats before or after training in an autoshaped lever-press response (a model of associative learning). The results show that 8-OH-DPAT improved consolidation of the conditioned response (CR) when injected post-training, but impaired it with pretraining administration. Both effects were time-dependent. When the compound was administered pre- or post-training to free-feeding or prefeeding animals, they did not learn the CR. When it was administered to retrained food-deprived animals, the compound was also inactive. However, with retrained animals on a free-feeding schedule, pre- or post-training administration of 8-OH-DPAT enhanced retrieval in a dose-dependent fashion. Pretraining administration of 8-OH-DPAT impaired food intake and exploration, and therefore learning. The present results strongly suggest a role of 5-HT1A receptors in the consolidation and retrieval of learning. Such improvement is independent of food intake.
Thirteen protein kinase inhibitors (PKIs) were investigated in chicks for their in vitro effects on PKC activity and for their in vivo effects on memory formation for a peak-avoidance task. Amnesia occurred by 15-30 min post-training when agents that inhibit primarily Ca2+/calmodulin were injected into brain. Amnesia occurred by 60 min post-training when agents that inhibit PKC-, PKA-, and/or PKG-dependent protein kinases, but not Ca2+/calmodulin, were injected. Enhancement of memory formation was accomplished by injecting bradykinin, but not forskolin. Both of these agents, however, attenuated the amnesia produced by H-7. These results are discussed as relevant neural processes involved in memory and synaptic plasticity.
Honeybee placode sensilla contain 18-35 olfactory receptor neurons. In insects, such neurons are thought to not interact with one another before reaching the central nervous system. Extracellular, multiunit recordings were made from the placodes and separated into spike shape classes, termed subplacode units. An analysis of the response spectra of subplacode units demonstrated that subplacode units with similar response spectra were more likely to be found in different placodes than in the same placode. An analysis was made of the mean interspike intervals and its variation for whole placodes and subplacode units. The coefficient of variation for whole placodes was less than that for subplacode units. Whole placode spike trains are therefore more uniform than subplacode spike trains, indicating that neurons might not be firing independently of each other. (C) 1994 Academic Press, Inc.
Reaction time (RT) is usually speeded and slowed to correctly and incorrectly cued target stimuli, respectively, in experiments on attention shift (Posner, 1988). When targets occur in a spatial location different from the cue, shifting attention from the cued location to the target location involves interrupt of ongoing activity, move attention to the new location, and reengage attention. The present study investigated whether the cognitive operations involved in cued vs uncued attentional shifts also were detectable in the event-related potentials (ERPs). Two experiments are reported, one with visual and one with auditory stimuli. In the visual modality, the cue and target were a lit-up square and an asterisk, respectively, shown on a computer screen. In the auditory modality, the cue was a tone in either the left or right ear, followed by the target noise in either the same or the opposite ear. The results from the visual experiment showed shorter RTs to correctly cued (Valid) targets and longer RTs to incorrectly cued (Invalid) targets. Invalidly cued targets elicited enhanced P3 amplitudes, with a frontocentral distribution. Reduced P3 amplitudes were observed on Valid trials, largest reduction for parietooccipital leads. The auditory experiment showed P3 enhancement frontally and reduced amplitudes at temporal and parietal leads. No RT differences were seen to Valid and Invalid trials. The existence of an anterior attention system involved in interrupt and disengage of attention, and a posterior attention facilitation system related to cue presentation is discussed.
Depending on dose and task requirements, ethanol can have either a facilitative or an impairing influence on learning. Some explanations for this dichotomy have considered ethanol's suppression of behavioral variability and processing of incidental stimuli (e.g., context). The present study examined the effect of ethanol on context and conditioned stimulus (CS) learning in the preweanling rat. To assess state-dependent effects, a drug dissociation design was used. Learning to both context and CS were analyzed within each dose of ethanol (0, 1.2, 1.6, or 2.0 g/kg) and a trend analysis was conducted to determine dose-response relationships as a function of train-test state. The 1.2 g/kg dose of ethanol did not affect conditioning to either the context or the CS. A 1.6 g/kg dose tended to disrupt context, but not CS, conditioning. The influence of 2.0 g/kg ethanol depended on train-test conditions. Ethanol administration prior to training resulted in the stronger impairment of CS learning while context conditioning was most disrupted if ethanol was given only prior to testing. The results suggest that ethanol selectively attenuates processing of stimuli, possibly dependent on relative saliency at the time of testing.
Long-term behavioral and neurochemical effects of bilateral lesions to only the infracallosal component of the ''so-called'' septohippocampal pathways (cingular bundle, fimbria and fornix) have not been assessed. This experiment compared the behavioral, histochemical and neurochemical effects of supracallosal (SUPRA; cingular bundle) and infracallosal (INFRA; fimbria-fornix) hippocampal denervations in Long-Evans female rats. The rats were tested, over two periods (8-52 and 92-170 days postlesion), for open field locomotion, spontaneous alternation and radial-maze performance. Subsequently, histochemical or neurochemical determinations of cholinergic, serotonergic and noradrenergic hippocampal innervations were performed using acetylcholinesterase-staining, determination of high-affinity synaptosomal uptake of choline and serotonin, and measurement of hippocampal serotonin and noradrenaline concentrations by HPLC methods. Whatever behavioral test was considered, no significant effect was found in rats with SUPRA lesions, whereas rats with INFRA lesions were permanently impaired in all tests. Histochemical and neurochemical analyses showed hippocampal cholinergic as well as serotonergic markers to be substantially decreased in INFRA rats as compared to SHAM and SUPRA rats. The SUPRA rats exhibited a weak but significant reduction of both serotonergic and noradrenergic markers compared to SHAM and INFRA rats. These results suggest that lesions limited to the infracallosal pathway induce a hippocampal denervation sufficient to account for most of the behavioral, histochemical and neurochemical deficits classically reported following extensive lesions of the anterior hippocampal connections. Since the behavioral and neurochemical deficits were found to be lasting, it is suggested that bilateral infracallosal damage to the septohippocampal pathways might constitute an interesting paradigm of partial hippocampal deafferentation to investigate the effects of neural grafts or other treatments in an animal model of Alzheimer's disease. (C) 1994 Academic Press, Inc.
We investigated the effect of a bilateral post-training intracerebral infusion of KN62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II (CaM-II), on memory. This enzyme plays a crucial role in the early phases of long-term potentiation. Male Wistar rats were implanted bilaterally with cannulae aimed at the CA1 region of the dorsal hippocampus or at the junction between the central and the basolateral nuclei of the amygdala. After recovery, rats were trained in step-down inhibitory avoidance using a 0.5-mA footshock and tested for retention 24 h later. At various times after training (0, 30, 120, or 240 min for the animals implanted into the hippocampus; 0 or 240 min for the animals implanted in the amygdala) they received, through the cannulae, an infusion of vehicle (0.1% dimethylsulfoxide in water) or KN62 (100 mumol/side). KN62 caused full retrograde amnesia when given 0 min after training into either the amygdala or the hippocampus. When given into the hippocampus 30 min post-training it had a partial amnestic effect. When given 120 min after training into the hippocampus, or 240 min after training into either structure, KN62 had no effect. The data suggest that the early phase of memory requires intact CaM-II activity in the amygdala and hippocampus and support the hypothesis that memory involves long-term potentiation initiated at the time of training in both structures.
The mushroom bodies of insects are believed to be involved in higher order sensory integration and learning. In the honeybee, the mushroom body can be separated into three different, modality-specific input compartments and several morphologically inseparable output regions. By means of morphometric analysis we show that the volumes of these subcompartments depend on both the age of the adult bee and its experience. For the most part a significant, age-dependent increase in neuropile volume is observed. Additionally, the olfactory and visual input regions show experience-related differences. Unlike other subcompartments, the visual input region does not change in volume with age, but only with experience. We thus suggest that experience is an important factor in the structural development of higher order brain regions of an insect, the honeybee. (C) 1994 Academic Press, Inc.
In four experiments with rats, the effects of the NMDA antagonist ketamine on several forms of gustatory learning were studied. Replicating previous findings, in Experiment 1 ketamine was shown to impair one-trial acquisition of a flavor aversion at the dose of 25 mg/kg, but also produced a significant state-dependency effect. In Experiment 2 ketamine did not alter the process of habituation of neophobia to a new flavor. Abolition of latent inhibition by ketamine injected before preexposure in Experiment 3a was not replicated in Experiment 3b when ketamine was injected before all phases of the experiment. Finally, in Experiment 4 rats injected with ketamine showed slower acquisition of a flavor aversion with a multiple-trial procedure but finally reached a level similar to that shown by saline controls. The implications of these results for an interpretation of the effects of ketamine on flavor aversion learning in terms of interference with flavor memory storage are discussed.
Biochemical investigations show that vasopressin interacts with noradrenalin to potentiate noradrenalin-induced accumulation of cyclic-AMP in the hippocampus, via the beta-adrenergic receptors. We previously showed in BALB/c mice that the effects of vasopressin (bilaterally injected at a 25-pg dose) in the ventral hippocampus were more effective than in the dorsal hippocampus on the retrieval and relearning of a Go-No Go visual discrimination task. Considering our results and those reported by biochemical investigations, we evaluated possible noradrenergic-vasopressinergic interaction in the ventral hippocampus under our behavioral conditions. To do so, we first explored the effects of propranolol and phentolamine, antagonists of beta- and alpha-adrenergic receptors, respectively. Second, we assessed the modifications in the vasopressin-induced improvement of retrieval and relearning by pretreating the subjects with either propranolol or phentolamine. Third, we tested the treatments in a locomotor activity task to determine whether the effects demonstrated in the two preceding experiments could be partially due to locomotor alterations by the drug. The results indicated that bilateral injection of propranolol (1 microgram on each side), which did not appear to affect the retention performance itself, completely blocked the enhancement of retrieval and relearning resulting from the vasopressin treatment. In contrast, bilateral injection of phentolamine (1 microgram on each side), which moderately improved retrieval, enhanced the vasopressin effect. The present results lend further support to the view that both noradrenalin and vasopressin play important roles in retrieval and relearning processes. More importantly, they provide additional support for the functional interaction of the noradrenergic and vasopressinergic hippocampal systems.
A passive avoidance-to-active avoidance negative transfer paradigm was used to investigate in rats the effects of glucose and fructose on recently acquired memories. Immediate post-passive avoidance conditioning injections of glucose, fructose, or saline were followed 48 h later by active avoidance conditioning. Equimolar 10, 32, 100, and 2000 mg/kg sc doses of the two sugars significantly impaired acquisition of the reversal task, whereas 3.2 mg/kg doses of both sugars were without significant effect on subsequent performance and 320 mg/kg doses of both sugars significantly enhanced subsequent performance. The cubic trends for both dose-response functions were statistically significant and did not differ from each other. This is the first demonstration that glucose and fructose affect recently acquired memories in accord with comparable cubic dose-response functions, and that there are doses of both sugars that can enhance memory (as indicated by an increase in the number of trials required to reach criterion on the reversal task) and doses of both sugars that can impair memory (as indicated by a decrease in the number of trials required to reach criterion on the reversal task), compared to saline treatment. The similar cubic dose-response functions for glucose and fructose suggest that their mechanisms of action when they are injected peripherally are similar. In addition, because fructose does not readily pass the blood-brain barrier, the results suggest that these two monosaccharides may act through a common peripheral pathway.
