应用MRI预扫描定位提高大鼠脑立体定位术的准确性

目的评价MRI预扫描方法在鼠脑穿刺定位准确性上的作用与价值。材料与方法选取健康雄性SD大鼠18只,随机分为2组,分别为MRI预扫描定位组（9只）,在MR图像指导下进行穿刺注射;以及经典穿刺组（9只）,不采用MR影像学检测定位,严格按照脑立体定位图谱进行穿刺注射。穿刺以通过苍白球中心的鼠脑切面中尾状核区为靶目标,穿刺后采用MRI影像学方法确定穿刺点位置,比较MRI预扫描定位穿刺与经典立体定位穿刺的准确度。结果 MRI预扫描定位组穿刺准确率为88.89%,经典穿刺组穿刺准确率为66.67%;两种方法的穿刺定位差异有显著性（P〈0.05）,MRI预扫描组的穿刺定位准确度明显高于经典穿刺组。结论 MRI预扫描可显著提高鼠脑立体定位穿刺的准确度,是进行立体定位精细穿刺的必要操作。     

The effects of naloxone,diprenorphine, and diazepam on responding suppressed by pre-shock and pre-food stimuli

The lever-pressing of rats was reinforced with food according to a variable-interval 1-min schedule. In one group, occasional illumination of cue lights for 30-sec periods was followed by a brief electric shock; responding was suppressed during these periods. Naloxone (0.01–10 mg/kg) did not change the degree to which responding was suppressed during the pre-shock stimulus. Diprenorphine (0.1–10 mg/kg) slightly attenuated suppression, and diazepam (1.0–3.0 mg/kg) increased responding during the stimulus to normal levels. These results confirm that opiate antagonists do not always enhance the effects of shock on behavior. In a second group, occasional illumination of the cue lights for 20-sec periods was followed by delivery of free food pellets. Responding was also suppressed during the pre-food stimulus. Neither naloxone nor diprenorphine had any effect on response rate during this stimulus. In contrast to the results of earlier studies using benzodiazepines, diazepam (1.0–3.0 mg/kg) produced a marked attenuation of response suppression during the pre-food stimulus.     

Extended exposure to a discriminated,limited-hold temporal schedule does not produce stimulus control

Four rats were exposed to two different stimuli (either lights or tones), each stimulus being correlated with independent probabilities of water delivery in a temporally defined schedule. The schedule consisted of a 60 s T cycle with 30 s t(D) and t(-) successive subcycles; t(D) was correlated with a probability of water delivery of 1.0 and t(-) was correlated with a probability of water delivery of 0.0. The schedule was maintained during 180 sessions and extended for 25 extra sessions omitting the stimulus in t(-). The four rats showed low frequencies of responding, response frequency being slightly higher in t(-) than in t(D). The percentage of lost reinforcers was independent of response frequency. The rats which lost less reinforcers were those which obtained more water deliveries during the first 15 cycles of each session. These results show that stimulus control does not develop in limited-hold temporal schedules, and that response-reinforcer effectiveness may depend on the initial contact with reinforcers in the first cycles of the session.     

Electrodermal discrimination with visual feedback in two incompatible stressful situations. A yoked control comparison

One group (N = 14) of human volunteers received three sessions of discriminated avoidance and punishment with the skin resistance response (SRR) as the instrumental behavior. Each session consisted of three 7 minute periods of Sidman avoidance (response-stimulus [R-S] and stimulus-stimulus [S-S] = 40 sec) of a 0.5 second, 15 Hz square wave shock mixed with three periods of punishment with the same shock. The avoidance and punishment periods were differentially signaled by red and green lights, and a circle appeared superimposed on the discriminative stimuli during a criterion SRR. A second group (N = 14) was yoked to the first by recording shock events on magnetic tape and shocking the yoked subject in the same temporal sequence. In both groups the visual feedback stimulus was consistently related to the subject's ongoing electrodermal behavior. As in previous research, the contingent shock subjects made significantly more SRRs during avoidance than during punishment in all three sessions. For yoked subjects the discrimination did not appear until the third session. The findings imply that the discrimination is at least partly independent of the avoidance and punishment contingencies, and they raise questions about the role of the feedback stimulus.     

Relevance of a neutral cue in a two-choice detection task in the rat

Relevance of a neutral cue for performance in a two-choice visuospatial detection task was examined. Nine rats were trained, 5 with short intertrial interval (ITI) and 4 with long ITI, to detect a target (lateral lights) presented after a neutral-cue (central light). The removal of the neutral-cue decreased accuracy and increased response latencies and omissions. These results demonstrate that a neutral-cue, preceding the target, is relevant for the performance, suggesting that rats are highly expectant during the neutral-cue and reallocate attentional resources during ITI. Furthermore, latencies were higher, omissions were lower and the fall of accuracy was greater for rats with long than with short ITI, which could indicate that the neutral-cue was more relevant for the former group.     

Tonic and phasic stimulus control of blood pressure responses using opposing unconditional stimuli

The transswitching paradigm was used in the present study to investigate the effects of tonic (long duration) environmental stimuli paired with opposing unconditional stimuli on human blood pressure. Sixty volunteers participated for two sessions, one week apart. Subjects were presented with a pseudorandom sequence of four trials of red lights (five minutes each) and four trials of blue lights (five minutes each) within each session. All subjects received the cold pressor test during the red lights. During the blue lights, half the subjects received warm water and the other half received a neutral temperature water. Subjects received the presentations of the water in one of three methods: as determined by the experimenter, preceded by a warning signal, or self-administered. The results indicated that conditional and unconditional responses during the red lights were progressive increases in blood pressure. During the blue lights associated with warm water, conditional and unconditional responses were often progressive decreases in blood pressure. The method of administration of the water affected the magnitude of the unconditional responses. Evidence for phasic stimulus control was not as unequivocal as tonic stimulus control. The present results indicated that it is possible to modify blood pressure in two directions (increases and decreases) when two high contrast, opposing unconditional stimuli are presented.     

The effects of cross-modal manipulations of attention on the detection of vibrotactile stimuli in humans

Although it is well known that attention to a visual or auditory stimulus can enhance its perception, less is known concerning the effects of attention on the perception of natural tactile stimuli. The present study was conducted to examine the magnitude of the effect of cross-modal manipulations of attention in human subjects on the detection of weak, low-frequency vibrotactile stimuli delivered to the glabrous skin of the finger pad of the right index finger via an Optacon. Three suprathreshold vibrotactile arrays (40 Hz), varying in the number of activated pegs and hence the area of skin stimulated, were used. Subjects were trained to detect the occurrence of vibrotactile or visual stimuli and to respond by pressing a foot pedal as quickly as possible thereafter. Two instructional lights were used to cue the subjects as to which stimulus modality they should attend, in three experimental conditions. In the first cue condition, the forthcoming stimulus modality was indicated by the illumination of its associated light. In the second cue condition, both instructional lights were illuminated, and the subjects were asked to divide their attention equally between the two modalities. In the third cue condition, the stimulus modality was falsely indicated by the illumination of the cue not associated with the stimulus to be presented. Reaction times (RTs) were calculated for each trial. For each modality, tactile and visual, the RTs varied significantly with the cue condition, with the mean RT changing in a graded manner across the experimental conditions (being shortest for the correctly cued condition, intermediate for the neutrally cued condition, and longest for the incorrectly cued condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serial conditional discrimination and temporal bisection in rats selectively lesioned in the dentate gyrus

In positive serial conditional discrimination, animals respond during a target stimulus when it is preceded by a feature stimulus, but they do not respond when the same target stimulus is presented alone. Moreover, the feature and target stimuli are separated from each other by an empty interval. The present work aimed to investigate if two durations (4 or 16 s) of the same feature stimulus (light) could modulate the operant responses of rats to different levers (A and B) during a 5-s target stimulus (tone). In the present study, lever A was associated with the 4-s light, and lever B was associated with the 16-s light. A 5-s empty interval was included between the light and the tone. In the same training procedure, the rats were also presented with the 5-s tone without the preceding light stimuli. In these trials, the responses were not reinforced. We evaluated the hippocampal involvement of these behavioral processes by selectively lesioning the dentate gyrus with colchicine. Once trained, the rats were submitted to a test using probe trials without reinforcement. They were presented with intermediate durations of the feature stimulus (light) to obtain a temporal bisection curve recorded during the exposure to the target stimuli. The rats from both groups learned to respond with high rates during tones preceded by light and with low rates during tones presented alone, which indicated acquisition of the serial conditional discrimination. The rats were able to discriminate between the 4- and 16-s lights by correctly choosing lever A or B. In the test, the temporal bisection curves from both experimental groups showed a bisection point at the arithmetic mean between 4 and 16 s. Such processes were not impaired by the dentate gyrus lesion. Thus, our results showed that different durations of a feature stimulus could result in conditional properties. However, this processing did not appear to depend on the dentate gyrus alone.     

Nicotine-evoked conditioned responding is dependent on concentration of sucrose unconditioned stimulus

Previous studies have shown that the interoceptive nicotine conditional stimulus (CS) functions similarly to exteroceptive CSs such as lights or environments. For instance, the appetitive conditioned response (CR) evoked when nicotine is repeatedly paired with sucrose presentations (the unconditioned stimulus; US) is sensitive to changes in training dose (CS salience) and the contiguity between the CS effects and sucrose. The current study was conducted to extend this research by examining the possible role of US intensity in CR acquisition and maintenance. Rats were trained using one of four sucrose concentrations: 0, 4, 16, or 32% (w/v). On nicotine sessions (0.4 mg base/kg), rats received 36 deliveries (4 s each) of their assigned concentration intermittently throughout the session; sucrose was withheld on saline sessions. In all groups, an appetitive goal-tracking CR was acquired at a similar rate. However, the asymptotic CR level varied with sucrose concentration. The magnitude of the CR was increased in rats trained with higher sucrose US concentrations. These findings are consistent with previous Pavlovian conditioning research, and extend the conditions under which the nicotine state functions as an interoceptive conditional stimulus.     

Effect of Isolation-Rearing on Conditioned Dopamine Release In Vivo in the Nucleus Accumbens of the Rat

Abstract: Intracerebral microdialysis in conjunction with HPLC coupled to electrochemical detection was used to investigate the effect of isolation-rearing in the rat on extracellular dopamine (DA) and its metabolites in vivo, in the shell region of the nucleus accumbens, in response to footshock and in relation to a conditioned emotional response. Male Lister hooded rats were reared from weaning for 6–8 weeks in either social isolation or groups of five. In the training phase, rats were exposed to a novel environment for 10 min where they experienced mild footshock. Footshock caused an immediate increase in basal extracellular DA levels in both rearing groups relative to control rats. However, the increase in extracellular DA was prolonged in the case of the isolation-reared rats and significantly greater than in group-reared rats. Exposure to the novel environment without shock (control groups) did not significantly alter basal extracellular DA in the nucleus accumbens shell; 140 min later rats were returned to the testing box (contextual stimulus) without receiving footshock. The contextual stimulus increased basal extracellular DA in the nucleus accumbens of both groups of rats with respect to controls; however, this increase was significantly greater and more prolonged in isolates. Extracellular levels of the metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid did not differ between isolation- and group-reared rats, and they were not significantly affected by either footshock or the contextual stimulus. These results suggest that exposure to footshock and a contextual stimulus are associated with increases in basal extracellular DA levels in the nucleus accumbens shell. The results also support evidence in favour of an isolation-induced enhancement in dopaminergic activity in the nucleus accumbens, which probably underlies aspects of the behavioural syndrome associated with isolation.     

Strategy of auditory discrimination of scale in Java sparrows: they use both "imagery" and specific cues

We examined whether Java sparrows use imagery of auditory stimuli (imagery is a subject's mental representation of a stimulus by which the subject's behaviour may be governed under stimulus control even in the absence of the physical stimulus). Three types of ascending tone sequences were used. In the intact scale, sequence tones were played in ascending order. In the intact-masked scale, part of the sequence was masked by noise but the remaining scale was identical with the intact scale, whereas in the violated scale, the sequence could be heard as if tones were played slowly (Experiment 1) or quickly (Experiment 2). Subjects were divided into two groups: one group was trained to respond to the intact and intact-masked scales and to suppress response to the violation scale (imagery-positive group). The contingency was reversed for the other (violation-positive) group. In Experiment 1, all the birds acquired discrimination, but successful transfer to novel stimuli was observed only in the imagery-positive group, suggesting that the imagery of the tone sequence was used as a discriminative cue. Experiment 2 confirmed that the stimulus duration was a discriminative cue for both groups, suggesting that the birds also acquired discrimination using only specific cues.     

The immune system response to antigen in cold- and warm-adapted rats

In rat experiments, it was shown that long-term adaptation to cold modified the response pattern of the immune system to antigen stimulus by variously changing the different components of the response. There was a considerable decrease in the number of antigen-binding cells in spleen and peritoneal exudate and also a marked decrease in general antibodies in blood. Conversely, the number of antibody-forming cells in spleen increased twofold. The shift in the thermal conditions after immunization caused changes in the immune response. After the placement of cold-adapted animals to the warm environments the number of antigen binds and antibody-forming cells in spleen, as well as hemagglutinin titers in serum normalized, became indistinguishable from those in the warm-adapted control group. The placement from warm to cold after immunization of warm-adapted rats also produced considerable shifts in parameters of the immune response. However, these shifts were not entirely consistent with those observed for long-term adapted to cold. The obtained data evidence that the thermal factor of the environment is of major importance to the function of immunocompetent cells.     

Levels of integration in cognitive control and sequence processing in the prefrontal cortex

Cognitive control is necessary to flexibly act in changing environments. Sequence processing is needed in language comprehension to build the syntactic structure in sentences. Functional imaging studies suggest that sequence processing engages the left ventrolateral prefrontal cortex (PFC). In contrast, cognitive control processes additionally recruit bilateral rostral lateral PFC regions. The present study aimed to investigate these two types of processes in one experimental paradigm. Sequence processing was manipulated using two different sequencing rules varying in complexity. Cognitive control was varied with different cue-sets that determined the choice of a sequencing rule. Univariate analyses revealed distinct PFC regions for the two types of processing (i.e. sequence processing: left ventrolateral PFC and cognitive control processing: bilateral dorsolateral and rostral PFC). Moreover, in a common brain network (including left lateral PFC and intraparietal sulcus) no interaction between sequence and cognitive control processing was observed. In contrast, a multivariate pattern analysis revealed an interaction of sequence and cognitive control processing, such that voxels in left lateral PFC and parietal cortex showed different tuning functions for tasks involving different sequencing and cognitive control demands. These results suggest that the difference between the process of rule selection (i.e. cognitive control) and the process of rule-based sequencing (i.e. sequence processing) find their neuronal underpinnings in distinct activation patterns in lateral PFC. Moreover, the combination of rule selection and rule sequencing can shape the response of neurons in lateral PFC and parietal cortex.     

Acquisition of visually guided conditional associative tasks in Göttingen minipigs

Fourteen Göttingen minipigs were trained on two different visually guided conditional associative tasks. In a spatial conditional task, a black stimulus signalled that a response to the left was correct, and a white stimulus signalled that a response to the right was correct. In a conditional go/no-go task, a blue stimulus signalled go, and a red stimulus signalled no-go. The pigs were trained until a behavioural criterion of 90% correct for each of two consecutive sessions. For the spatial conditional task, all pigs reached this criterion in 520 trials or less. For the conditional go/no-go task, all pigs, except three, reached this criterion in 1600 trials or less. Sows and boars learned equally fast. The tasks can be useful for the testing of cognitive function in pig models of human brain disorders.     

Influence of haptic guidance in learning a novel visuomotor task

In (re)learning of movements, haptic guidance can be used to direct the needed adaptations in motor control. Haptic guidance influences the main driving factors of motor adaptation, execution error, and control effort in different ways. Human-control effort is dissipated in the interactions that occur during haptic guidance. Minimizing the control effort would reduce the interaction forces and result in adaptation. However, guidance also decreases the magnitude of the execution errors, which could inhibit motor adaptation. The aim of this study was to assess how different types of haptic guidance affect kinematic adaptation in a novel visuomotor task. Five groups of subjects adapted to a reaching task in which the visual representation of the hand was rotated 30°. Each group was guided by a different force field. The force fields differed in magnitude and direction in order to discern the adaptation based on execution errors and control effort. The results demonstrated that the execution error did indeed play a key role in adaptation. The more the guiding forces restricted the occurrence of execution errors, the smaller the amount and rate of adaptation. However, the force field that enlarged the execution errors did not result in an increased rate of adaptation. The presence of a small amount of adaptation in the groups who did not experience execution errors during training suggested that adaptation could be driven on a much slower rate and on the basis of minimization of control effort as was evidenced by a gradual decrease of the interaction forces during training. Remarkably, also in the group in which the subjects were passive and completely guided, a small but significant adaptation occurred. The conclusion is that both minimization of execution errors and control effort drives kinematic adaptation in a novel visuomotor task, but the latter at a much slower rate.     

Performance of mice in an automated olfactometer: odor detection, discrimination and odor memory

Mice were trained on a variety of odor detection and discrimination tasks in 100- or 200-trial sessions using a go, no-go discrete trials operant conditioning procedure. Odors, presented for 1 s on each trial, were generated by an air dilution olfactometer (for threshold tests) and an easily constructed eight-channel liquid dilution unit (for two- and multiple-odor discrimination tasks). Mice rapidly acquired the operant task and demonstrated excellent stimulus control by odor vapors. Their absolute detection threshold for ethyl acetate was similar to that obtained with rats using similar methods. They readily acquired four separate two-odor discrimination tasks and continued to perform well when all eight odors were presented in random order in the same session and when reinforcement probability for correct responding was decreased from 1 to 0.5. Memory for these eight odors, assessed under extinction after a 32 day rest period, was essentially perfect. Time spent sampling the odor on S+ and S- trials was highly correlated with response accuracy. When accuracy was at chance levels (e.g. initial trials on a novel task), stimulus sampling time on both S+ and S- trials was approximately 0.5-0.7 s. As response accuracy increased, sampling time on S+ trials tended to increase and remain higher than sampling time on S- trials.     

The role of temporal generalization in a temporal discrimination task

Two experiments trained rats to discriminate two or three stimulus durations using a temporal discrimination task. A standard peak shift effect was observed when training was administered with short versus long signals in Experiment 1. Both discrimination accuracy scores and the generalization gradients revealed that shorter intervals were discriminated more accurately, which may be due to the scalar property of timing. In Experiment 2, three signals (short, medium, and long) were associated with three different responses, or two of the intervals were associated with one response (short and long or short and medium) and the other interval with a different response. Here, the short/medium versus long discrimination was learned most readily of the three tasks. The results of both experiments indicated a strong contribution of learning of individual durations combined with scalar generalization gradients, but Experiment 2 indicated that categorical encoding of durations may have also been operating.     

Response strategies during acquisition of serial learning in pigeons (Columba livia)

Pigeons were exposed on fixed duration sessions to four chromatic stimuli and trained to perform a 2-item sequence. A detailed analysis of incorrect responses performed on each trial prior to completion of the sequence led to distinguish three learning stages. Already on initial sessions animals responded significantly more frequently to relevant stimuli than to irrelevant ones indicating stimulus control by salience. During an intermediary stage, responding to item 2 increased significantly and animals started an increasing number of trials with item 2, suggesting stimulus control by recency. On the final session the correct sequence outnumbered significantly the reverse sequence, suggesting control by order, while recency and salience effects were present to a lesser extent. Repeated pecks, i.e. consecutive pecks on the same cue, occurred on the four cues on the first session and decreased significantly on the last session for irrelevant colours. In addition, when key pecks were followed by a brief sound signal, repeats on relevant stimuli decreased while efficient colour pecks (i.e. when repeats were ignored) on these stimuli increased. These findings are discussed in the light of those obtained in traditional chaining paradigms.     

Adrenal-mediated depression of N-acetyltransferase activity and melatonin levels in the rat pineal gland

N-acetyltransferase (NAT) is believed to be the rate-limiting enzyme in the synthesis of melatonin from serotonin in the pineal gland. Norepinephrine released from sympathetic nerve endings within the pineal gland stimulates NAT activity and, therefore, melatonin synthesis. When an animal is subjected to a stressful stimulus, it would be expected that the increase in plasma stimulus, it would be expected that the increase in plasma catecholamines originating from the adrenal medulla and/or the sympathetic nervous system would result in a stimulation of pineal NAT activity. Adult male rats were given a 1.5cc injection of physiological saline subcutaneously into the back leg. Compared to non-injected controls, animals stressed in this manner were shown to have significantly lower pineal melatonin content 10 min after the saline injection late in the light phase of the light/dark cycle (at 18.30 h-lights on at 07.00 h). To test this more thoroughly, a time course study was conducted during the dark phase (at 02.00 h-5 hours after lights out) when pineal NAT activity and melatonin levels are either increasing or elevated. NAT activity and melatonin levels in the pineal were significantly depressed in stressed animals as compared to controls by 10 min after the saline injection, and remained so until 60 min after injection. By 90 min they had returned to control values. In the next study the nighttime response of the pineal to stress was compared in intact and adrenalectomized rats. Adrenalectomy prevented the changes in NAT activity and melatonin content associated with the saline injection. Some factor, such as a catecholamine or corticosterone from the adrenal, seems to be eliciting the response in the pineal to the saline injection. It is not known if the factor is acting centrally or directly on the pineal gland.     

Speed and Accuracy of Visual Motion Discrimination by Rats

Animals must continuously evaluate sensory information to select the preferable among possible actions in a given context, including the option to wait for more information before committing to another course of action. In experimental sensory decision tasks that replicate these features, reaction time distributions can be informative about the implicit rules by which animals determine when to commit and what to do. We measured reaction times of Long-Evans rats discriminating the direction of motion in a coherent random dot motion stimulus, using a self-paced two-alternative forced-choice (2-AFC) reaction time task. Our main findings are: (1) When motion strength was constant across trials, the error trials had shorter reaction times than correct trials; in other words, accuracy increased with response latency. (2) When motion strength was varied in randomly interleaved trials, accuracy increased with motion strength, whereas reaction time decreased. (3) Accuracy increased with reaction time for each motion strength considered separately, and in the interleaved motion strength experiment overall. (4) When stimulus duration was limited, accuracy improved with stimulus duration, whereas reaction time decreased. (5) Accuracy decreased with response latency after stimulus offset. This was the case for each stimulus duration considered separately, and in the interleaved duration experiment overall. We conclude that rats integrate visual evidence over time, but in this task the time of their response is governed more by elapsed time than by a criterion for sufficient evidence.