对听感觉运动门控自上而下调节的动物模型和神经机制

对惊反射的前脉冲抑制是减少干扰影响、保护脑内信息加工的重要机制。它既是研究感觉运动门控的模型, 也是探究精神分裂症机制的模型。前脉冲抑制可被选择性注意和情绪等高级认知活动所调节。本论文工作围绕着恐惧条件化和知觉空间分离去掩蔽(空间选择性注意)对听觉前脉冲抑制多层次化的自上而下调节, 在大鼠行为模型、神经通路、神经电生理机制等几个层次上开展了系统性研究, 并引入了精神分裂症的神经发育模型, 证实早期社会隔离饲养对前脉冲抑制注意调节的破坏影响。本论文研究成果不仅对认识正常情况下脑在复杂刺激场景中的信息加工机制有重要意义, 以感觉运动门控认知调节功能缺失为基础的动物模型也将推动精神分裂症心理学和神经生物学机制的研究。     

Second-order conditioning of human causal learning

This article provides the first demonstration of a reliable second-order conditioning (SOC) effect in human causal learning tasks. It demonstrates the human ability to infer relationships between a cause and an effect that were never paired together during training. Experiments 1a and 1b showed a clear and reliable SOC effect, while Experiments 2a and 2b demonstrated that first-order extinction did not affect SOC. These results were similar to those found in animal and human conditioning and suggested that a similar associative mechanism could explain these effects. However, they can also be used to look into the underlying causal mental model people build and store while they are learning this task. From a cognitive view, overall results suggest that an independent rather than a chain causal mental model is stored after second-order learning in human causal tasks.     

Nonuniform effects of reinstatement within the time window

A time window is a limited period after an event initially occurs in which additional information can be integrated with the memory of that event. It shuts when the memory is forgotten. The time window hypothesis holds that the impact of a manipulation at different points within the time window is nonuniform. In two operant conditioning experiments with 68 3-month-old human infants, we tested the predictive validity of the nonuniformity principle for reinstatement—a partial training trial that forestalls forgetting. After demonstrating that 3-month-olds forget the training task after 5 days (Experiment 1), we presented a reinstatement early (immediately), midway (3 days), or late (5 days) in the time window (Experiment 2). Retention increased exponentially with the reinstatement delay. The surprising magnitude of this result, plus its generality across tasks and species, strongly suggests that the timing of reinstatement differentially affects the outcomes of studies on learning and memory.     

Intrahippocampal insulin improves memory in a passive-avoidance task in male wistar rats

The main impacts of insulin favor the peripheral organs. Although it functions as a neuropeptide, insulin possesses also some central effects. The aim of this study was to determine the effect of intrahippocampal infusion of insulin on passive avoidance learning in healthy male rats. Thirty male wistar rats were divided into three groups (n=10 each). The experimental group had posttraining insulin infusion into the CA1 region of dorsal hippocampus, after which they were compared with sham (saline) and control (intact) groups. Insulin treated animals had greater latency to enter the dark compartment in compare with saline treated (p=0.023) or control groups (p=0.017). Upon our results, we concluded that intrahippocampal injections of insulin may enhance memory for a simple learning task which supports the concept that insulin possibly plays an endogenous role in memory formation.     

Beyond Fear Emotional Memory Mechanisms in the Human Brain

ABSTRACT— Neurobiological accounts of emotional memory have been derived largely from animal models investigating the encoding and retention of memories for events that signal threat. This literature has implicated the amygdala, a structure in the brain's temporal lobe, in the learning and consolidation of fear memories. Its role in fear conditioning has been confirmed, but the human amygdala also interacts with cortical regions to mediate other aspects of emotional memory. These include the encoding and consolidation of pleasant and unpleasant arousing events into long-term memory, the narrowing of focus on central emotional information, the retrieval of prior emotional events and contexts, and the subjective experience of recollection and emotional intensity during retrieval. Along with other mechanisms that do not involve the amygdala, these functions ensure that significant life events leave a lasting impression in memory.     

Anxiety-related biases in children's avoidant responses to a masked angry face

While anxious children often show escape and withdrawal behaviours towards threats, few studies have experimentally assessed avoidance. The present study examined whether children with high levels of anxiety showed more avoidant responses to a neutral conditioned cue (CS+) that was paired with an unconditioned threat stimulus (UCS), a masked angry facial expression. Thirty-six 10 and 11 year-olds participated in a task, which involved choosing between two CS card stimuli of different colours to win points. Whilst both cards awarded the same number of points, one colour was systematically paired with a masked angry face (CS+), whilst the other colour was paired with a masked neutral face (CS-). Children with higher anxiety scores had an overall tendency to choose the card associated with the neutral face, with some evidence suggesting that this tendency emerged gradually across trials. These results suggest a relationship between anxiety and stimulus-response learning for CS+-UCS associations that support behavioural avoidance.     

Fear conditioning in posttraumatic stress disorder: evidence for delayed extinction of autonomic, experiential, and behavioural responses

Aversive conditioning has been proposed as an important factor involved in the etiology of posttraumatic stress disorder (PTSD). However, it is not yet fully understood exactly which learning mechanisms are characteristic for PTSD. PTSD patients (n=36), and healthy individuals with and without trauma exposure (TE group, n=21; nTE group, n=34), underwent a differential fear conditioning experiment consisting of habituation, acquisition, and extinction phases. An electrical stimulus served as the unconditioned stimulus (US), and two neutral pictures as conditioned stimuli (CS+, paired; CS-, unpaired). Conditioned responses were quantified by skin conductance responses (SCRs), subjective ratings of CS valence and US-expectancy, and a behavioural test. In contrast to the nTE group, PTSD patients showed delayed extinction of SCRs to the CS+. Online ratings of valence and US-expectancy as well as the behavioural test confirmed this pattern. These findings point to a deficit in extinction learning and highlight the role of affective valence appraisals and cognitive biases in PTSD. In addition, there was some evidence that a subgroup of PTSD patients had difficulties in learning the CS-US contingency, thereby providing preliminary evidence of reduced discrimination learning.     

Interoceptive fear conditioning as a learning model of panic disorder: an experimental evaluation using 20% CO(2)-enriched air in a non-clinical sample

Despite the role afforded interoceptive fear conditioning in etiologic accounts of panic disorder, there are no good experimental demonstrations of such learning in humans. The aim of the present study was to evaluate the interoceptive conditioning account using 20% carbon dioxide (CO(2))-enriched air as an interoceptive conditioned stimulus (CS) (i.e., physiologically inert 5-s exposures) and unconditioned stimulus (US) (i.e., physiologically prepotent 15-s exposures). Healthy participants (N=42) were randomly assigned to one of three conditions: a CS-only, contingent CS-US pairings, or unpaired/non-contingent CS and US presentations. Electrodermal and self-report (e.g., distress, fear) served as indices of conditioned emotional responding. Results showed greater magnitude electrodermal and evaluative fear conditioning in the paired relative to the CS-only condition. The explicitly unpaired condition showed even greater electrodermal and evaluative responding during acquisition, and marked resistance to extinction. The latter results are consistent with the possibility that the unpaired procedure constituted a partial reinforcement procedure in which CO(2) onset was paired with more extended CO(2) exposure on 50% of the trials. Overall, the findings are consistent with contemporary learning theory accounts of panic.     

Electrical stimulation of the pedunculopontine tegmental nucleus in freely moving awake rats: time- and site-specific effects on two-way active avoidance conditioning

The pedunculopontine tegmental nucleus (PPTg) is involved in the regulation of thalamocortical transmission and of several functions related to ventral and dorsal striatal circuits. Stimulation of the PPTg in anesthetized animals increases cortical arousal, cortical acetylcholine release, bursting activity of mesopontine dopaminergic cells, and striatal dopamine release. It was hypothetized that PPTg stimulation could improve learning by enhancing cortical arousal and optimizing the activity of striatal circuits. We tested whether electrical stimulation (ES) of the PPTg, applied to freely-moving awake rats previously implanted with a chronic electrode, would improve the acquisition and/or the retention of two-way active avoidance conditioning, and whether this effect would depend on the specific PPTg region stimulated (anterior vs posterior) and on the time of ES: just before (pre-training) or after (post-training) each of three training sessions. The treatment consisted of 20 min of ES (0.2 ms pulses at 100 Hz; current intensity: 40-80 microA). The results showed that (1) this stimulation did not induce either any signs of distress nor abnormal behaviors, apart from some motor stereotyped behaviors that disappeared when current intensity was lowered; (2) pre-training ES applied to the anterior PPTg improved the acquisition of two-way active avoidance, (3) no learning improvement was found after either post-training ES of the anterior PPTg, or pre- and post-training ES of the posterior PPTg. The results give support to a role of PPTg in learning-related processes, and point to the existence of functional PPTg regions.     

Biphasic ERK1/2 activation in both the hippocampus and amygdala may reveal a system consolidation of contextual fear memory

There is accumulating evidences to suggest that memory consolidation in some conditions involves two waves of neuronal plastic change. Using two fear conditioning procedures in male C57BL/6J mice, we have recently shown that consolidation of the foreground contextual fear memory required two waves of ERK1/2 activation in hippocampal CA1, while consolidation of cue conditioning was only associated with the early phase of activation. The present experiment further showed that this bi-phasic pattern of ERK1/2 activation was not restricted to hippocampal CA1, but could also be observed in other fear memory-related brain areas. The unpaired conditioning procedure (context in foreground) induced two waves of ERK1/2 activation in hippocampal CA1 and CA3, as well as in the LA and BLA nuclei of the amygdala. In contrast, the paired conditioning procedure (context in background) led to a transient early phase only in hippocampal CA1 and LA. In addition, ERK1/2 phosphorylation in the hippocampus was found to correlate with that in the amygdala nuclei specifically after the unpaired procedure. Taken together, our data suggest that the observed biphasic pattern of neuronal plastic events may reflect the interplay between hippocampal and amygdala activity-dependent plasticity critical for the system consolidation of contextual fear memory.