[Superior colliculus-pulvinar-amygdala subcortical visual pathway and its biological significance].

Superior colliculus-pulvinar-amygdala pathway is one of the subcortical visual pathways in mammalian brain. Some recent studies suggest that this pathway is involved in processing emotion-related visual information. This review discusses the possibility that this pathway is more related to visual alert rather than simply the early visual information processing. The biological significance of this pathway is also discussed. Instead of detecting "where" or "what" the visual target is, the task of this early visual stage is to send out a warning signal, i.e., "something appears", so that the brain can be set up in a state of alert, which is important for the survival of animals. Thus, in the early visual information process, detection of new object "emerging" or "disappearing" takes priority over the acquisition of its feature information of "texture" and "shape", etc. The subcortical pathway may provide the neural basis of early visual warning in topological perception, a biological significance critical for animal survival.

Environmental cue difference and training duration modulate spatial learning and cue preference in detour task.

In this study, we investigated how different environmental cue and the proficiency of body motion influenced detour learning behaviour and cue preference in cue conflict situations. Domestic chicks were trained to detour around an obstacle and follow a fixed route to rejoin with their partners. When the environmental cue was red versus blue vertical stripes, the chicks learned the detour task quicker, and as the number of training trials after route acquisition increased, they switched their preference from the environmental cue to a body-motion cue in the cue conflict test. On the other hand, when the environmental cue was vertical versus horizontal blue stripes, the chicks learned the detour task slower and showed a dependence on the body-motion cue regardless of the number of training trials performed after route acquisition. When the environmental cue was removed, most chicks could still successfully detour according to the specific route on which they had been trained. Furthermore, a significant difference in detour latency was found between chicks using the environmental cue and chicks using the body-motion cue, suggesting separate neuronal circuits responsible for processing the two types of information. Our results demonstrated that young domestic chicks could use both environmental cue and body-motion cues to memorize the route during the detour learning task; however, the detour route preference could be dynamically modulated by difference of the environmental cue and the number of training trials they received.

Increasing top-down suppression from prefrontal cortex facilitates tactile working memory.

Navigated transcranial magnetic stimulation (TMS) combined with diffusion-weighted magnetic resonance imaging (DW-MRI) and tractography allows investigating functional anatomy of the human brain with high precision. Here we demonstrate that working memory (WM) processing of tactile temporal information is facilitated by delivering a single TMS pulse to the middle frontal gyrus (MFG) during memory maintenance. Facilitation was obtained only with a TMS pulse applied to a location of the MFG with anatomical connectivity to the primary somatosensory cortex (S1). TMS improved tactile WM also when distractive tactile stimuli interfered with memory maintenance. Moreover, TMS to the same MFG site attenuated somatosensory evoked responses (SEPs). The results suggest that the TMS-induced memory improvement is explained by increased top-down suppression of interfering sensory processing in S1 via the MFG-S1 link. These results demonstrate an anatomical and functional network that is involved in maintenance of tactile temporal WM.

Pentylenetetrazole-induced status epilepticus following training does not impair expression of morphine-induced conditioned place preference.

Learning and memory play an important role in morphine addiction. Status epilepticus (SE) can impair the spatial and emotional learning and memory. However, little is known about the effects of SE on morphine-induced conditioned place preference (CPP). The present study was designed to investigate the effects of SE on morphine CPP, with food CPP being used as a control. The effects of SE on spatial memory in the Morris water maze (MWM) and Y-maze were investigated. SE was induced in adult mice using intraperitoneal injection of pentylenetetrazole; control mice received saline. The data indicated that SE had no effects on the formation of morphine CPP; however, the formation of food CPP was blocked by SE. Meanwhile, spatial memory assayed in the MWM and Y-maze was impaired by SE. In addition, the data demonstrated that SE did not cause a lasting disturbance of motor activity nor a change in the mice's appetite. These results suggested that although SE had no effects on morphine CPP, there was impaired food CPP and spatial memory in both the MWM and the Y-maze. The mechanisms underlying memory process of morphine CPP may be different from other types of memory.

Maze model to study spatial learning and memory in freely moving monkeys.

Many types of mazes have been used in cognitive brain research and data obtained from those experiments, especially those from rodents' studies, support the idea that the hippocampus is related to spatial learning and memory. But the results from non-human primates researches regarding the role of the hippocampus in spatial learning and memory are controversial and inconsistent with those obtained in rodents. This might be due to the differences of the methods used in non-human primates and rodents. Several kinds of maze models including two-dimensional computerized visual maze models and three-dimensional maze models have been developed for non-human primates, but they all have some defects. Therefore, development of a maze model for non-human primates that is comparable with those used in rodents is necessary to solve the controversy. This paper describes a large-scale, three-dimensional outdoor maze model for non-human primates which can be used to study spatial learning and memory. Monkeys learn to use the maze quickly compared with two-dimensional computerized visual mazes. It has many advantages which could make up the limits of the existing three-dimensional mazes in non-human primates, and can be comparable with radial arm mazes used in rodents. Based on the results, we believe that the new maze model will be valuable in many research areas, especially in studies involving spatial learning and memory in freely moving monkeys.

Morphine and propranolol co-administration impair consolidation of Y-maze spatial recognition memory.

In the present study, the interaction between morphine and the beta-adrenergic receptor antagonist, propranolol (PROP), in memory consolidation was investigated in a two-trial recognition Y-maze task. Four sets of Y-maze experiments were carried out in mice, with 2 and 4 h inter-trial intervals (ITI) and all drugs administered immediately after the training trials. In the first and second sets of experiments, post-training administration of morphine (0.25 and 2.5 mg/kg) or PROP (2, 10 and 20 mg/kg) alone did not impair memory consolidation after a 2 h ITI. However, in the third and fourth sets of experiments, co-administration of these ineffective doses of morphine (0.25 and 2.5 mg/kg) and PROP (2, 10 and 20 mg/kg) disrupted memory consolidation after a 2 h ITI. Moreover, the relatively higher dose of morphine (2.5 mg/kg) plus the relatively higher doses of PROP (10 and 20 mg/kg) disrupted memory consolidation to a greater extent after a 2 h ITI. Locomotor activity was not affected by any of the drug treatments. Our data shows that morphine and PROP co-administration disrupts the consolidation of spatial recognition memory, suggesting that inactivation of the beta-adrenergic system may contribute to morphine-induced impairment of memory.

Anodal Transcranial Direct-Current Stimulation Over the Right Dorsolateral Prefrontal Cortex Influences Emotional Face Perception.

The dorsolateral prefrontal cortex (DLPFC) is considered to play a crucial role in many high-level functions, such as cognitive control and emotional regulation. Many studies have reported that the DLPFC can be activated during the processing of emotional information in tasks requiring working memory. However, it is still not clear whether modulating the activity of the DLPFC influences emotional perception in a detection task. In the present study, using transcranial direct-current stimulation (tDCS), we investigated (1) whether modulating the right DLPFC influences emotional face processing in a detection task, and (2) whether the DLPFC plays equal roles in processing positive and negative emotional faces. The results showed that anodal tDCS over the right DLPFC specifically facilitated the perception of positive faces, but did not influence the processing of negative faces. In addition, anodal tDCS over the right primary visual cortex enhanced performance in the detection task regardless of emotional valence. Our findings suggest, for the first time, that modulating the right DLPFC influences emotional face perception, especially faces showing positive emotion.

Heroin impairs map-picture-following and memory tasks dependent on gender and orientation of the tasks.

Male and female heroin-dependent patients (HDPs) matched with "normal" people were tested on 4 topographical orientation tasks: schematic map-following, map-memory, schematic picture-following, and picture-memory tasks. The results showed that, in general, female HDPs demonstrated greater performance deficits in map-following and map-picture-memory tasks than did other participants. In the map-picture-following tasks, participants showed a preference for turning right versus turning left, reflected by lower correct scores and longer latencies in completing left-oriented tasks. In contrast, no difference in orientation preference was found for participants in memory tasks, except for female HDPs. Asymmetric dopamine receptor distribution in the brain, sex steroidal hormone, brain areas related to motor functioning and working memory, and gender-dependent lateralization may be involved in the different effects of heroin and rightward bias between men and women.

[Dynamics of hippocampal sensory gating during the chronic morphine administration, withdrawal and re-exposure to morphine in rats].

Drug addiction is considered as a chronic, recurrent brain disease characterized by relapse. Repeated exposure to certain drugs, such as morphine, can produce deleterious sequelae, such as drug dependence, tolerance and compulsive drug seeking. In the present study, we investigated the dependence and psychological craving for morphine in rats using the conditioned place preference (CPP) paradigm. On the other hand, to study the effect of morphine on hippocampal sensory gating (N40), double click auditory-evoked potential was recorded during the chronic morphine administration, withdrawal and re-exposure to morphine in rats. The rats in morphine group received a course of morphine (10 mg/kg, i.p.) injection for 12 d, followed by 12 d of withdrawal, 1 d of re-exposure to morphine (2.5 mg/kg, i.p.) and 2 d of the second withdrawal. The rats in the control group were treated in the same way except that saline was applied instead of morphine. CPP test demonstrated that the method of drug administration in the present study induced dependence and psychological craving for morphine in rats. The results in the double click auditory-evoked potential experiment showed that during the chronic morphine administration, hippocampal N40 gating was damaged. In the initial 2 d of the first withdrawal hippocampal N40 gating in morphine group was reduced compared with that in the control group and it was significantly greater on the 3rd day, and then recovered gradually to the normal level from day 4 to day 12. After re-exposure to morphine, hippocampal N40 gating in morphine group was significantly reduced compared with that in the control group, and it remained at a lower level during the following 2 d, suggesting that hippocampal N40 gating in rats was more sensitive to morphine during re-exposure. Our results suggest that long-term repeated morphine administration and re-exposure to morphine disrupt hippocampal N40 gating, and that the effect of morphine addiction on the brain is possibly long-term.

Differently lasting effects of prenatal and postnatal chronic clozapine/haloperidol on activity and memory in mouse offspring.

UNLABELLED: We evaluated the behavioral effects of chronic haloperidol (HAL) and clozapine (CLO) during gestation and CNS development, compared with transient treatments that stopped 1-3 weeks before the test. RESULTS: 1) Chronic HAL (6 mg/l in drinking water) but not HAL-withdrawal caused hypo-activity in open-field test on postnatal days (PNDs) 35, 42 and 56. However, hyper-activity was found in both CLO (90 mg/l) and CLO-withdrawal pups. 2) In the step-through test, retention performance was significantly higher in HAL-treated mice than in the controls on PND 42, as well as in withdrawal mice on PNDs 35 and 42. However, both chronic CLO (90 mg/l) exposure and CLO-withdrawal tended to improve the acquisition of memory. Furthermore, chronic CLO (180 mg/l) ameliorated scopolamine (3 mg/kg)-induced impairment of memory on PND 56. 3) In the water-maze test, both chronic HAL and HAL-withdrawal treatments significantly impaired performance on the 4th training day at PND 35, but not PNDs 42 and 56. Neither chronic CLO exposure nor CLO-withdrawal affected spatial memory. 4) Body weight following HAL/CLO administration decreased when compared with the controls during PND 21-35, but approached control levels at PND 40. CONCLUSION: HAL doesn't elicit permanent behavioral changes in offspring. By contrast, CLO had longer-lasting effects than HAL. The pups at age before PND 35 seem more sensitive to HAL/CLO than elder pups.

Rhesus monkey neural stem cell transplantation promotes neural regeneration in rats with hippocampal lesions.

Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells. Therefore, neural stem cell transplantation can be used to promote functional recovery of the nervous system. Rhesus monkey neural stem cells (1 × 105 cells/µL) were injected into bilateral hippocampi of rats with hippocampal lesions. Confocal laser scanning microscopy demonstrated that green fluorescent protein-labeled transplanted cells survived and grew well. Transplanted cells were detected at the lesion site, but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum. Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall, and integrated into the recipient brain. Behavioral tests revealed that spatial learning and memory ability improved, indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.

Early adversity contributes to chronic stress induced depression-like behavior in adolescent male rhesus monkeys.

Chronic stress is an important cause for depression. However, not everyone who is exposed to chronic stress will develop depression. Our previous studies demonstrated that early adversity can cause lasting changes in adolescent rhesus monkeys, but depressive symptoms have not been observed. Compared to adults, it is still unknown that whether adolescent rhesus monkeys experiencing early adversity are more likely to develop depressive symptoms. In this study, we investigated the long term relationship between early adversity, chronic stress and adolescent depression for the first time. Eight male rhesus monkeys were reared in maternal separation (MS) or mother-reared (MR) conditions. All of them went through unpredictable chronic stress for two months at their age four. The stressors included space restriction, intimidation, long illumination and fasting. Behavioral and physiological data were collected during the experiment. The results showed that, compared with the MR group, the locomotor activity of MS group was significantly decreased after one month of chronic stress while huddling up and stereotypical behaviors were significantly increased. Moreover, this trend continued and even worsened at the second month. Significantly higher hair cortisol levels and lower body weight were observed in MS group after two months of stress. These results indicate that early adversity is one of the environmental factors which can increase the susceptibility of depression when experiencing chronic stress in the later life. This will further clarify the important roles of early environmental factors in the development of adolescent depression and children rearing conditions should receive more attention.

Prefrontal dysfunction and a monkey model of schizophrenia.

The prefrontal cortex is implicated in cognitive functioning and schizophrenia. Prefrontal dysfunction is closely associated with the symptoms of schizophrenia. In addition to the features typical of schizophrenia, patients also present with aspects of cognitive disorders. Based on these relationships, a monkey model mimicking the cognitive symptoms of schizophrenia has been made using treatment with the non-specific competitive N-methyl-D-aspartate receptor antagonist, phencyclidine. The symptoms are ameliorated by atypical antipsychotic drugs such as clozapine. The beneficial effects of clozapine on behavioral impairment might be a specific indicator of schizophrenia-related cognitive impairment.

Spatially directed movement and neuronal activity in freely moving monkey.

The abilities to plan a series of movements and to navigate within the environment require the functions of the frontal and ventromedial temporal lobes, respectively. Neuropsychological studies posit the existence of egocentric (prefrontal) and allocentric (ventromedial temporal) spatial frames of reference that mediate these functions. To examine neural mechanisms underlying egocentric and allocentric guidance of movement, we have developed behavioral and neurophysiological techniques for freely moving monkey. In this chapter, we provide evidence that the dorsolateral prefrontal cortex is important for egocentric spatial tasks in both the visual and tactile modalities, but it does not contribute to performance of an allocentric spatial task. Moreover, neurophysiological recordings indicate that prefrontal neurons are involved in monitoring the spatial nature of behavioral sequences in an egocentric memory task. In contrast, hippocampal neurons are active during spatially directed locomotion, apparently reflecting the monkey's location in a testing room. This discharge is independent of the task's contingencies.

Reinforcement-related neurons in the primate basal forebrain respond to the learned significance of task events rather than to the hedonic attributes of reward.

The objective of this study was to determine if the responses of basal forebrain neurons are related to the cognitive processes necessary for the performance of behavioural tasks, or to the hedonic attributes of the reinforcers delivered to the monkey as a consequence of task performance. In all cases, it was found that the primary neuronal responses were to visual stimuli that required analysis important for the selection of a behavioural response and not to the delivery of reinforcement per se. Indeed, reinforcement-related neurons that responded only to the delivery of juice or of saline were never encountered. In additional experiments, it was found that abstract visual cues-specific gestures of the experimenter-that signaled the impending delivery of reinforcement were able to activate these neurons. These data are consistent with the view that reinforcement-related basal forebrain neurons influence the sensory and motor processes in the cerebral cortex, providing control signals that optimise the processing of complex sensory stimuli and/or the generation of appropriate behavioural responses.

Dissociation of egocentric and allocentric spatial processing in prefrontal cortex.

Monkeys with lesions of areas 9 and 46 performed three variants of the spatial delayed response (SDR) task. There were no impairments in allocentric spatial memory in which geometrical relationships between environmental cues were used to identify spatial location; thus, memory of a 3D environmental map is intact. In contrast, there were severe impairments in egocentric spatial memory guided by visual or tactile cues that monkeys can relate to their viewing perspective during testing. These results strongly suggest that dorsolateral prefrontal cortex selectively mediates spatial memory tasks that are solved by referencing the location of targets to the body's orientation.

A microelectrode drive for long term recording of neurons in freely moving and chaired monkeys.

An electrode drive is described for recordings of neurons in freely moving and chaired monkeys during the performance of behavioural tasks. The electrode drives are implanted for periods of up to 6 months, and can advance up to 42 electrodes using 14 independent drive mechanisms. The drive samples 288 points within a 12 mmx12 mm region, with 15 mm of electrode travel. Major advantages are that recordings are made in freely moving monkeys, and these recordings can be compared with those in chaired experiments; waveforms of single neurons are stable, enabling prolonged recordings of the same neurons across periods of days; recordings can be made throughout the brain, including the dorsolateral prefrontal cortex and hippocampus; the drive accommodates both sharp microelectrodes and fine wire assemblies such as tetrodes.

Effect of paradoxical sleep deprivation and stress on passive avoidance behavior.

Previous studies have shown that several types of stress can induce memory impairment. However, the memory effects of paradoxical sleep deprivation (PSD), a stressor in itself, are unclear. We therefore compared passive avoidance behavior of rats undergoing PSD and PSD stress yoked-control (PSC) using the "reversed flowerpot method." When rats were kept isolated on a PSC platform for 24 h immediately after criterion training, retention trials showed impaired aversive memory storage. When delayed for 24 h after criterion training, PSC stress did not disrupt retention performance. In rats subjected to PSD, either immediately or 24 h after criterion training, there was no disruption of aversive memory consolidation. These results suggest that, during stress, paradoxical sleep plays a role in erasing aversive memory traces, in line with the theory that we "dream in order to forget."

[Methods for single unit recording in behavioring morphine craving rat].

In this paper, one method was introduced, which was a combination of the cue-related morphine addiction model and a technique for obtaining chronic extracellular recordings of single unit in freely moving rats. With the combination and improvement of this technique, we have successfully applied this new method to study the neuronal activity of the hippocampus CA1 region in morphine withdrawal rats. In all, we found some more accurate and objective cellular characteristics of hippocampal neurons, and considered these characteristics as one of electrophysiological indexes of morphine addiction rats.

Face recognition increases during saccade preparation.

Face perception is integral to human perception system as it underlies social interactions. Saccadic eye movements are frequently made to bring interesting visual information, such as faces, onto the fovea for detailed processing. Just before eye movement onset, the processing of some basic features, such as the orientation, of an object improves at the saccade landing point. Interestingly, there is also evidence that indicates faces are processed in early visual processing stages similar to basic features. However, it is not known whether this early enhancement of processing includes face recognition. In this study, three experiments were performed to map the timing of face presentation to the beginning of the eye movement in order to evaluate pre-saccadic face recognition. Faces were found to be similarly processed as simple objects immediately prior to saccadic movements. Starting ∼ 120 ms before a saccade to a target face, independent of whether or not the face was surrounded by other faces, the face recognition gradually improved and the critical spacing of the crowding decreased as saccade onset was approaching. These results suggest that an upcoming saccade prepares the visual system for new information about faces at the saccade landing site and may reduce the background in a crowd to target the intended face. This indicates an important role of pre-saccadic eye movement signals in human face recognition.