Reversible hippocampal lesions disrupt water maze performance during both recent and remote memory tests

Conventional lesion methods have shown that damage to the rodent hippocampus can impair previously acquired spatial memory in tasks such as the water maze. In contrast, work with reversible lesion methods using a different spatial task has found remote memory to be spared. To determine whether the finding of spared remote spatial memory depends on the lesion method, we reversibly inactivated the hippocampus with lidocaine either immediately (0-DAY) or 1 mo (30-DAY) after training in a water maze. For both the 0-DAY and 30-DAY retention tests, rats that received lidocaine infusions exhibited impaired performance. In addition, when the 0-DAY group was retested 2 d later, (when the drug was no longer active), the effect was reversed. That is, rats that had previously received lidocaine performed as well as control rats did. These findings indicate that the rodent hippocampus is important for both recent and remote spatial memory, as assessed in the water maze. What determines whether remote spatial memory is preserved or impaired following disruption of hippocampal function appears to be the type of task used to assess spatial memory, not the method used to disrupt the hippocampus.     

The effects of aging and dorsal hippocampal lesions: performance on spatial and nonspatial comparable versions of the water maze

Aged intact and young hippocampal-lesioned rats show similar deficits on the spatial water maze. However, this does not necessitate that the source of these deficits in the aged animals is due to hippocampal damage. These water maze deficits may arise from other aging factors such as changes in thermoregulation, muscle fatigue, swim ability, and response to stress. Consequently, it is imperative to examine the performance of aged rats on a comparable nonhippocampal version of this task. Past attempts to develop a hippocampus-independent version of the water maze were confounded because these tasks were easier (i.e., the rats spent much less time swimming in the water) than the spatial versions of the task. The current study examined performance on a hippocampus-independent task comparable in difficulty to the spatial water one. Middle-aged (16-m) and old (25-m) male F344 rats were given sham or dorsal hippocampus lesions and tested on both a spatial and a nonspatial water maze. The middle-aged rats with hippocampal lesions were impaired on the spatial task but not on the nonspatial task. Conversely, aged animals showed a similar impairment on both types of water maze tasks. Additionally, hippocampal lesions exacerbated the age-related impairment on both tasks. These findings indicate that caution must be used when interpreting the results of water maze tasks for aged animals.     

Impairment of spatial learning and hippocampal synaptic potentiation in c-kit mutant rats

The c-kit receptor tyrosine kinase encoded by the white-spotting (W) gene is highly expressed in rat hippocampal CA1–CA4 regions. We found an impaired spatial learning and memory in homozygous c-kit (Ws/Ws) mutant rats that have a 12-base deletion in the tyrosine kinase domain of the c-kit gene and a very low kinase activity. Electrophysiological studies in hippocampal slices revealed that the long-term potentiation (LTP) induced by the tetanic stimulation (100 Hz, 1 sec) in the mossy fiber (MF)–CA3 pathway, but not in the Schaffer collaterals/commissural–CA1 pathway, was significantly reduced in c-kit mutants compared with wild-type (+/+) rats. The paired-pulse facilitation (PPF) was measured before the tetanus and after the establishment of the LTP in each slice. The initial PPF in the MF–CA3 pathway positively correlated with the amplitude of the LTP in the wild-type rats but not in the c-kit mutant rats. Furthermore, they failed to show the normal characteristics observed in the MF–CA3 pathway of +/+ rats; that is, the negative correlation between the initial PPF and the changes in PPF measured after the LTP. These findings suggest an involvement of SCF/c-kit signaling in hippocampal synaptic potentiation and spatial learning and memory.     

Kv4 potassium channels modulate hippocampal EPSP-spike potentiation and spatial memory in rats

Kv4 channels regulate the backpropagation of action potentials (b-AP) and have been implicated in the modulation of long-term potentiation (LTP). Here we showed that blockade of Kv4 channels by the scorpion toxin AmmTX3 impaired reference memory in a radial maze task. In vivo, AmmTX3 intracerebroventricular (i.c.v.) infusion increased and stabilized the EPSP-spike (E-S) component of LTP in the dentate gyrus (DG), with no effect on basal transmission or short-term plasticity. This increase in E-S potentiation duration could result from the combination of an increase in excitability of DG granular cells with a reduction of GABAergic inhibition, leading to a strong reduction of input specificity. Radioactive in situ hybridization (ISH) was used to evaluate the amounts of Kv4.2 and Kv4.3 mRNA in brain structures at different stages of a spatial learning task in naive, pseudoconditioned, and conditioned rats. Significant differences in Kv4.2 and Kv4.3 mRNA levels were observed between conditioned and pseudoconditioned rats. Kv4.2 and Kv4.3 mRNA levels were transiently up-regulated in the striatum, nucleus accumbens, retrosplenial, and cingulate cortices during early stages of learning, suggesting an involvement in the switch from egocentric to allocentric strategies. Spatial learning performance was positively correlated with the levels of Kv4.2 and Kv4.3 mRNAs in several of these brain structures. Altogether our findings suggest that Kv4 channels could increase the signal-to-noise ratio during information acquisition, thereby allowing a better encoding of the memory trace.     

Flexible memory processing by rats: use of prospective and retrospective information in the radial maze

Four experiments investigated the content of the memory used by rats in mediating retention intervals interpolated during performance in a 12-arm radial maze. The delay occurred following either the 2nd, 4th, 6th, 8th, or 10th choice. A 15-min delay had the greatest disruptive effect when interpolated in the middle of the choice sequence and less of an effect when it occurred either earlier or later. This pattern of results was obtained when either a free- or forced-choice procedure was used prior to the delay and regardless of whether postdelay testing consisted of completion of the maze or two-alternative forced-choice tests. Assuming that the disruptive effect of a delay is a function of memory load, this implies that the rats used information about previously visited arms (retrospective memory) following an earlier interpolated delay but information about anticipated choices (prospective memory) following a delay interpolated late in the choice sequence. There appeared to be a recency effect only in the early and middle delay conditions. This provides converging evidence for the dual-code hypothesis. No evidence for prospective memory was obtained following a 60-min delay.     

Sex differences and estropausal phase effects on water maze performance in aged rats

An age-related decline in memory has been reported in male rats; however, there are few studies that have addressed these changes in aged female rats. In young female rats, hormonal cycles influence behavior. By the age of 22 months most female rats have not had regular hormonal cycles for at least 9 months. In the current study we examined how the hormonal status (persistent estrus and pseudo-pregnant) of the aged (22-24 months) female rat (Long Evans) influenced performance on a spatial version of the Morris water maze and compared this to aged male rats. Aged females in persistent estrus showed better performance on the water maze than both aged females that were pseudopregnant and aged males. Thus, postestropausal hormonal status may influence the course of aging in females.     

Beacon training in a water maze can facilitate and compete with subsequent room cue learning in rats

In Stage 1 of 4 experiments in which rats completed a water-maze blocking procedure, experimental groups were trained to use a predictive beacon (hanging above, connected to, or displaced from the platform) to find a submerged escape platform in the presence of predictive or irrelevant background cues and in the presence or absence of irrelevant landmarks. In Stage 2, a fixed beacon, landmarks, and background cues all predicted the platform location. A Room Test (landmarks and background cues only) showed that Stage 1 training with a fixed hanging beacon or the moving displaced beacon facilitated Stage 2 learning of predictive room cues for experimental relative to control subjects. In contrast, Stage 1 training with a moving pole beacon interfered with Stage 2 learning about predictive room cues relative to controls, whereas training with a fixed pole or moving hanging beacon had no effect. We conclude that multiple spatial learning processes influence locating an escape platform in the water maze.     

Predator (cat hair)-induced enhancement of hippocampal long-term potentiation in rats: involvement of acetylcholine

Extensive literature has demonstrated that arousal and fear modify memory acquisition and consolidation. Predator hair and odors increase arousal in rats and, therefore, may influence information encoding and synaptic plasticity in the rodent nervous system. In behavioral experiments, we confirm that laboratory-bred Long Evans rats avoid cat hair. Electrophysiological work in vivo showed that long-term potentiation (LTP) in the dentate gyrus induced by perforant path stimulation was enhanced for 5-7 days when LTP induction occurred in the presence of cat hair relative to fake hair. The muscarinic receptor antagonist scopolamine (i.p.) reversed the cat hair-elicited LTP enhancement without affecting weaker LTP elicited in the presence of fake hair. Thus, exposure to a predator stimulus elicits a cholinergically-dependent state of heightened plasticity that may serve to facilitate information storage in hippocampal circuits.     

Post-training administration of corticosterone enhances consolidation of contextual fear memory and hippocampal long-term potentiation in rats

This study was designed to examine the effect of corticosterone on consolidation of contextual fear memory and hippocampal long-term potentiation (LTP) in rats. In Experiment 1, dose–response effects of corticosterone on consolidation of contextual fear memory were determined. Immediately after training in contextual fear conditioning task, rats received different doses of corticosterone. Testing 24 h later, it revealed that corticosterone enhanced memory consolidation in an inverted U shape as evidenced in increased freezing behavior of corticosterone-treated animals. The most effective dose was 3 mg/kg. In Experiment 2, LTP was examined in rats whose memory consolidation has been enhanced with corticosterone. The rats were trained as the above and received corticosterone (3 mg/kg) immediately after training. Immediately or up to one day after retention test, rats were anesthetized with urethane for LTP experiments. For LTP induction, three episodes of high frequency stimuli, 30 s apart, were delivered to the perforant path, each consisting of 10 stimuli at 250 Hz. LTP was assessed by measuring the increase in the initial slope of the population excitatory post-synaptic potentials and the amplitude of the population spikes. Data indicated that animals whose memory has been enhanced by corticosterone, also displayed enhanced hippocampal LTP. The above findings suggest that glucocorticoids may enhance contextual fear memory consolidation via enhancing hippocampal LTP.     

Fischer 344 and wistar rats differ in anxiety and habituation but not in water maze performance

The fact that various neuropharmacological substances have anxiolytic as well as amnesic effects suggests that neuronal mechanisms of anxiety and learning/memory closely interact. Hence, we hypothesized that differences in anxiety-related behavior could be accompanied with differences in cognition or habituation. Two rat strains with different levels of anxiety, more anxious Fischer 344 rats by Charles River (FC) and less anxious Wistar rats by Winkelmann (WW), were tested in the Morris water maze task and an open field test for habituation learning. Additionally, we investigated the effect of different light intensities on the performance in the Morris water maze and the elevated plus maze. The results of the water maze task indicate that differences in anxiety-related behavior do not go along with differences in this performance of learning/memory. Moreover, the test was not affected by different light intensities. In contrast, illumination did affect performance in the elevated plus maze test, wherein dim light provoked an anxiolytic effect in both rat strains. The findings that neither different baseline levels of anxiety nor fear modulating light conditions were accompanied by changes in the performance of rats in the Morris water maze led us to the suggestion that there is no connection between anxiety and learning/memory in this task. Contrarily, anxiety might be associated with habituation learning in the open field test, shown by the superior habituation of the anxious FC rats in comparison to the less anxious WW rats. In sum, these results indicate that anxiety and learning/memory seem to be independently regulated behaviors, whereas habituation might be more closely correlated with anxiety. Nevertheless, a general statement about the relation between emotionality and learning/memory mechanisms would be premature and the link between behaviors remains to be clarified.     

Temperamental contributions to children's performance in an emotion-word processing task: a behavioral and electrophysiological study

Seven-year-old children (N=65) participating in a study of the influence of infant temperament on socioemotional development performed an auditory selective attention task involving words that varied in both affective (positive vs. negative) and social (social vs. nonsocial) content. Parent report of contemporaneous child temperament was also collected, and individual differences in self-regulation in the affective (soothability) and cognitive (attentional control) domains were noted. Overall, children showed slower responses to stimuli that were either social or negative in content, with the largest effect elicited by words that possessed both traits. Children rated high in soothability and attentional control showed slower responses to social negative words. The other children showed little to no differential response patterns across the word categories. ERPs collected during the task indicated that processing differences were evident in the later more cognitive components of the ERP, especially in children low in attentional control. These findings indicate that performance on an auditory selective attention task can assist in identifying underlying patterns of affective processing.     

Breaking the cycle: cognitive behavioral therapy and biofeedback training in a case of cyclic vomiting syndrome

The present article presents a case of cognitive behavioral therapy (CBT) along with heart rate variability (HRV) biofeedback training for the treatment of a medication unresponsive 13-year-old boy with cyclic vomiting syndrome (CVS). CVS is characterized by recurring stereotypic episodes of vomiting, interspersed with asymptomatic periods. Triggers for vomiting include anticipatory anxiety related to school examinations, family conflicts, and birthday parties as well as infectious diseases, and certain foods. Current treatment design addressed two pivotal etiological factors: autonomic dysregulation and anticipatory anxiety. Treatment outcome suggests that vomiting episodes may be successfully prevented by aiding the patient to identify and manage precipitant psychological stressors, to regulate HRV patterns, and gain a renewed sense of bodily control and self-efficacy. Further research is suggested using a controlled study with pre- and post-behavioral and stress measures to evaluate the effectiveness of CBT and biofeedback training compared to pharmacotherapy and placebo.     

Emotional responses and memory performance of middle-aged CD1 mice in a 3D maze: effects of low infrared light

Non-thermal near infra-red (IR) has been shown to have many beneficial photobiological effects on a range of cell types, including neurons. In the present study, a pretreatment with a daily 6 min exposure to IR1072 for 10 days yielded a number of significant behavioral effects on middle-aged female CD-1 mice (12-months) tested in a 3D-maze. Middle-aged mice show significant deficits in a working memory test and IR treatment reversed this deficit. Interestingly, the IR treated middle-aged group despite making less memory errors than sham middle-aged group spent longer time in different parts of the maze than both the young group (3-months) and sham-middle-aged group (12-months). Young mice appeared more anxious than middle-aged mice in the first sessions of the test. Exposure to IR appeared to have no significant effects upon exploratory activity or anxiety responses. However, it elicited significant effects on working memory, with the IR middle-aged mice being more considerate in their decision making, which results in an overall improved cognitive performance which is comparable to that of young CD-1 mice. The present study describes a novel method for assessing emotional responses and memory performance in a 3D spatial navigation task and demonstrates the validity of our new all-in-one test and its sensitivity to ageing and non-invasive beneficial IR treatment.     

Neonatal tactile stimulation enhances spatial working memory, prefrontal long-term potentiation, and D1 receptor activation in adult rats

Environmental stimuli during neonatal periods play an important role in the development of cognitive function. In this study, we examined the long-term effects of neonatal tactile stimulation (TS) on spatial working memory (SWM) and related mechanisms. We also investigated whether TS-induced effects could be counteracted by repeated short periods of maternal separation (MS). Wistar rat pups submitted to TS were handled and marked transiently per day during postnatal days 2–9 or 10–17. TS/MS pups were stimulated in the same way as TS pups and then individually separated from their mother for 1 h/day. Their nontactile stimulated (NTS) siblings served as controls. In adulthood, TS and TS/MS rats showed better performance in two versions of the delayed alternation task and superior in vivo long-term potentiation of the hippocampo–prefrontal cortical pathway when compared with controls. Furthermore, there were more doses of A77636 (a selective dopamine D1 agonist) to significantly improve SWM performance in TS and TS/MS rats than in NTS rats, suggesting that activation of prefrontal D1 receptors in TS and TS/MS rats is more optimal for SWM function than in NTS rats. MS did not counteract TS-induced effects because no significant difference was found between TS/MS and TS animals. These data indicate that in early life, external tactile stimulation leads to long-term facilitative effects in SWM-related neural function.     

Distinct subsystems for the parafoveal processing of spatial and linguistic information during eye fixations in reading

Two experiments examined readers' use of parafoveally obtained word length information for word recognition. Both experiments manipulated the length (number of constituent characters) of a parafoveally previewed target word so that it was either accurately or inaccurately specified. In Experiment 1, previews also either revealed or denied useful orthographic information. In Experiment 2, parafoveal targets were either high- or low-frequency words. Eye movement contingent display changes were used to show the intact target upon its fixation. Examination of target viewing duration showed completely additive effects of word length previews and of ortho-graphic previews in Experiment 1, viewing duration being shorter in the accurate-length and the orthographic preview conditions. Experiment 2 showed completely additive effects of word length and word frequency, target viewing being shorter in the accurate-length and the high-frequency conditions. Together these results indicate that functionally distinct subsystems control the use of parafoveally visible spatial and linguistic information in reading. Parafoveally visible spatial information appears to be used for two distinct extralinguistic computations: visual object selection and saccade specification.     

Taste potentiation of auditory aversions in rats (Rattus norvegicus): a case for spatial contiguity

An aversion for an auditory stimulus was established in laboratory rats when a tone was spatially and temporally contiguous with a novel taste in a food conditioned stimulus compound followed by toxicosis. The procedure involved varying the location of the tone relative to a novel tasting food. During toxicosis conditioning, one group ate sweet food with a speaker located in the food, two groups ate sweet food with the speaker displaced (near or far) from the food, and a fourth group was presented with a tone without food available. It was found that the potentiation of auditory aversions required both the presence of a novel taste and spatial contiguity between the taste and the tone.     

Equal performance but distinct behaviors: sex differences in a novel object recognition task and spatial maze in a highly social cichlid fish

Animal Cognition - Sex differences in behavior and cognition can be driven by differential selection pressures from the environment and in the underlying neuromolecular mechanisms of...