Molecular Manipulations of Extracellular Superoxide Dismutase: Functional Importance for Learning

Extracellular superoxide dismutase (EC-SOD) controls the availability of extracellular superoxide (O ₂ ^- ), which is important for a variety of physiological pathways, including the primary means of inactivating nitric oxide (NO). The role of EC-SOD in neurobehavioral function has been until now unexplored. In the current studies, the phenotypic expression of genotypic alterations of EC-SOD production in mice were characterized for spatial learning and memory. Dramatic impairments in spatial learning in the win-shift 8-arm radial maze were seen in both EC-SOD knockout mice and EC-SOD overexpressing mice. The EC-SOD overexpressing mice were further characterized as having significant deficits in a repeated acquisition task in the radial-arm maze, which permitted the dissociation of long and short-term learning. Long-term learning was significantly impaired by EC-SOD overexpression, whereas short-term learning was not significantly affected by EC-SOD overexpression. NO systems have been shown to be importantly involved in learning and memory. This may be important in the current studies because EC-SOD has primary control over the inactivation of NO. We found that EC-SOD overexpressing mice were resistant to the cognitive effects of L-NAME (N^G-nitro-L-arginine methyl ester hydrochloride), an NO synthase inhibitor. Decreased NO catabolism in these mice may have served to counter the effects of NOS inhibition by L-NAME. The current finding that EC-SOD levels that were either higher or lower than controls impaired learning demonstrates that the proper control of brain extracellular (O ₂ ^- ) may be more vital than merely reduction of brain extracelluar (O ₂ ^- ) in maintaining adequate learning function.     

Conditioned taste aversion using four different means to deliver sucrose to rats

A solution of sucrose either to be drunk from a drinking tube-self-drinking procedure (SD)-or perfused intraorally as a consequence of nose-pokes-self-administration procedure (SA)-or perfused as a consequence of licking an empty tube (LA)-was paired with an LiCl-induced malaise in rats. The effects were compared to those of a procedure consisting of intraoral administration (IO) of sucrose not contingent to any specific action of the rat. Similar levels of conditioned taste aversion (CTA) were obtained but extinction in the IO procedure was quicker than in the SA procedure, which was itself quicker than in the SD procedure. Extinctions in the IO and LA procedures resembled one another and were quicker than in the SD procedure. A step towards deciding between several explanatory hypotheses of these differences was made by conducting two more experiments. The third experiment was based on reinstatement, or not, of the conditioning procedure for the test after standard IO extinction. CTA was produced only when SD was used both at conditioning and test. A fourth experiment was based on latent inhibition where the procedure was changed, or not, between preexposure and conditioning. Latent inhibition was absent only when the rats had been preexposed to sucrose with the SA procedure and conditioned with the SD procedure.     

Impairment and recovery of visual functions after bilateral lesions of superior colliculus

Adult, male hooded rats were tested on a six-choice jumping stand apparatus designed to study their ability to perform visually guided orientation movements with a brightness discrimination task. Upon reaching criterion, the rats suffered either one- or two-stage, bilateral electrolytic lesions of the superior colliculi and then, after a brief recovery period, were retested for their ability to retain the preoperatively learned task and, in addition, perform a more difficult task. Although both brain damaged groups evidenced an impairment in comparison to sham-operated controls, the rats with two-stage lesions were less disabled than their simultaneously operated counterparts.     

Studies on cortical field potentials recorded during learning processes of visually initiated hand movements in monkeys

Summary A monkey was trained to lift a lever by wrist extension in response to a light stimulus. During the learning process of the task over several months, field potentials related not only to the task performance but also to substitution and stimulation experiments were recorded with chronically implanted electrodes on the surface and at a depth of 2.5–3.0 mm in the prefrontal, premotor, motor and prestriate cortices. In the substitution experiment, an examiner lifted a lever for the monkey so that it was watching the light and rewarded without the hand movement. In the stimulation experiment, the same light stimulus was simply delivered to the monkey. In a naive monkey which lifted the lever independently of the stimulus, stimulus-locked potentials were evoked by the task experiment in those cortices except the motor cortex, but none was elicited by the substitution or stimulation experiment. In a welltrained monkey, the substitution and stimulation experiments induced almost the same potentials as those prior to the task movement in respective cortices except the motor cortex, in which the component of cerebellar-induced premovement potential was not observed during the substitution and stimulation experiments. At an intermediate stage of learning, the situation was intermediate between the naive and well-trained stages and most premovement potentials except those in the motor cortex were elicited by the substitution experiment in reduced sizes, but nothing by the stimulation experiment.The present study suggests that the neuronal circuits for the operantly conditioned movement are functionally organized and gradually consolidated in the learning process, and that the consolidation is made earlier for the circuit involving association and premotor cortices than the circuit including the motor cortex in the process. The circuit to the motor cortex via the cerebro-cerebellar interconnection is recruited only on the execution of movement.     

Interference between velocity-dependent and position-dependent force-fields indicates that tasks depending on different kinematic parameters compete for motor working memory

Humans demonstrate motor learning when exposed to changes in the dynamics of movement or changes in the visuomotor map. However, when two opposing dynamic transformations are learned in succession, the memory of the first is overwritten by learning of the second; the same is true for two opposing visuomotor rotations. This retrograde interference is not seen for all combinations of transformations, however. When a dynamic transformation is learned subsequent to a visuomotor rotation, the presence or absence of interference appears to depend crucially on the structure of the dynamic task: a force-field dependent on the position of the hand produces interference, whereas an inertial load applied lateral to the hand does not. To explain these results, it has been hypothesized that two transformations can be learned without interference if they depend on two different kinematic parameters of movement (such as position and velocity of the hand). Here we demonstrate, contrary to this hypothesis, interference between a dynamic transformation that depends on the position of the hand and one that depends on its velocity. However, the interference was found to be incomplete, supporting the view that the ability to retain motor memories for different tasks depends on the degree to which their representations conflict in working memory.     

A neural network-based similarity index for clustering DNA microarray data

A common approach to the analysis of gene expression data is to define clusters of genes that have similar expression. A critical step in cluster analysis is the determination of similarity between the expression levels of two genes. We introduce a neural network-based similarity index as a non-linear similarity index and compare the results with other proximity measures for Saccharomyces cerevisiae gene expression data. We show that the clusters obtained using Euclidean distance, correlation coefficients, and mutual information were not significantly different. The clusters formed with the neural network-based index were more in agreement with those defined by functional categories and common regulatory motifs.     

Operant conditioning studies of taste discrimination in the pigeon (Columba livia)

In the conditioning procedure employed in this study, pigeons were trained to dip their bills into a container and then to peck either at a left or at a right key, depending on whether the container was full of distilled water or of a solution of the substance being tested. The discrimination thresholds found (from one bird each) were 2 g/l (0.034 M) for NaCl, 2 g/l (0.024 M) for NaHCO₃, 1 g/l (0.013 M) for KCl, 0.5 g/l (0.005 M) for KHCO₃. Following the same procedure, two birds were then faced with the choice between the solution of the known substance and of a novel one. A higher degree of discrimination was found between NaHCO₃ and KHCO₃ than between NaHCO₃ and NaCl; in the latter case, choices appeared to be mostly based on the concentration of the two substances.     

非言语型学习障碍儿童社会信息加工的特点

目的: 探讨非言语型学习障碍儿童社会信息加工特点.方法: 本研究为病例对照研究.根据确定学习障碍儿童的标准,先确定学习障碍儿童,然后对学习障碍儿童进行韦氏儿童智力测验,根据测验结果把学习障碍儿童进一步分为非言语型学习障碍组(23人)、言语型学习障碍组(28人),然后按1:1比例选取对照组(51人).设置儿童与同伴、成人相互作用的三类情景,每类情景又分为模糊和清晰两种情况,对三组儿童进行结构性访谈.结果: ①清晰权威情景下.非言语型学习障碍儿童的编码数显著低于对照组儿童[(2.35±1.15)vs.(3.25±1.27),P＜0.01];对人物意图的判断,非言语型学习障碍儿童选择"恶意"的比率(65%)高于言语型学习障碍儿童(29%)(P＜0.05);在工具效能感上,非言语型学习障碍儿童选择有效的比率(74%)高于言语型学习障碍儿童(36%)(P＜0.05).②非言语型学习障儿童在每个情景故事下的总反应数都显著低于对照组儿童[模糊同伴加入情景:(1.17±0.49)vs.(1.09±0.86).P＜0.01;清晰同伴加入情景:(1.09±0.28)vs.(1.69±0.96),P＜0.01;模糊同伴激惹情景:(1.09±0.41)V8.(1.49±0.78),P＜0.05;清晰同伴激惹情景:(1.17±0.49)vs.(1.65±0.95),P＜0.05:模糊权威情景:(0.96±0.36)vs.(1.37±0.72),P＜0.01;清晰权威情景:(1.00±0.30)vs.(1.37±0.59),P＜0.01].结论: ①清晰权威情景下,非言语型学习障碍儿童编码精确性不如对照组儿童;对他人意图的判断非言语型学习障碍儿童比言语型学习障碍儿童倾向于敌意归因;非言语型学习障碍儿童比言语型学习障碍儿童工具效能感高.②在每个情景下,非言语型学习障碍儿童比对照组儿童生成策略少,反应不灵活.     

Scaling of smooth anticipatory eye velocity in response to sequences of discrete target movements in humans

We investigated the ability to generate anticipatory smooth pursuit to sequences of constant velocity (ramp) stimuli of increasing complexity. Previously, it was shown that repeated presentation of sequences composed of four ramps with two speeds in two directions, evoked anticipatory smooth pursuit after only one or two presentations. Here, sequences of four or six ramps, each having a choice of four speeds and either one or two directions (uni- or bi-directional) were examined. The components of each sequence were presented as discrete ramps (duration: 400 ms; randomised velocity: 10–40°/s), each starting from the centre with 1,200 ms periods of central fixation between ramps, allowing anticipatory activity to be segregated from prior eye movement. Auditory warning cues occurred 600 ms prior to each target presentation. Anticipatory smooth eye velocity was assessed by calculating eye velocity 50 ms after target onset (V ₅₀), prior to the availability of visual feedback. Despite being required to re-fixate centre during inter-ramp gaps, subjects could still generate anticipatory smooth pursuit with V ₅₀ comparable to single speed control sequences, but with less accuracy. In the steady state V ₅₀ was appropriately scaled in proportion to upcoming target velocity for each ramp component and thus truly predictive. Only one to two repetitions were required to attain a steady-state for unidirectional sequences (four or six ramps), but three or four repeats were required for bi-directional sequences. Results suggest working memory can be used to acquire multiple levels of velocity information for prediction, but its use in rapid prediction is compromised when direction as well as speed must be retained.     

Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice

Neuromedin B (NMB) is a mammalian bombesin (BN)-like peptide that exerts its function via the neuromedin B receptor (NMB-R). The NMB/NMB-R system is involved in stress response, and therefore we examined behavioral properties in female mice lacking NMB-R using a restraint-induced stress paradigm. Thirty minutes of restraint in a wire mesh cage constituted a sufficient stress stimulus for mice as evidenced by elevated blood glucose concentrations in stressed wild-type and NMB-R-deficient mice. Using a one-trial passive avoidance test, stressed NMB-R-deficient mice exhibited a marked reduction in memory performance. NMB-R-deficient mice exhibited elevated spontaneous activity in a novel environment compared to non-stressed mutant mice after 30-min stress, and a similar difference was also observed between stressed/non-stressed wild-type mice. An elevated plus maze test showed that the stress stimulus had no effect on anxiety in either wild-type or NMB-R-deficient mice. Furthermore, pain response of wild-type and NMB-R-deficient mice induced by electric foot shock was not affected under either stressed or non-stressed conditions. These results indicate that impaired memory performance in stressed NMB-R-deficient mice is not a consequence of changes in spontaneous activity, anxiety, or pain response, and suggest that the NMB/NMB-R pathway may play a role in regulating the stress response via the neural system that controls learning and memory.