Generalization of Habituation and Intrinsic Sensitization in the Leech

Using the shortening reflex of the medicinal leech Hirudo medicinalis we examined stimulus generalization of habituation learning. Preparations received mechanosensory stimulus at two positions on the leech body wall, one site used to carry out habituation training and a second novel site to test for generalization of habituation. After training, the specific mechanosensory neurons activated by each stimulus were assessed using intracellular recordings. As expected, the closer the two sites were to each other, the greater the degree of generalization of habituation at the novel site and the more sensory cells were shared. However, a form of behavioral facilitation was observed at the trained site that resembled behavioral sensitization, but differed from the standard sensitization process in several respects. (1) Facilitation was induced by stimulation of the novel site before habituation training at the trained site, although the stimulus intensity at the novel site was equivalent to the training stimuli and was not the strong, noxious stimuli that normally induce sensitization. (2) The magnitude of the facilitating effect was proportional to the proximity of the novel and trained stimulation sites. (3) Although behavior at the trained site was facilitated, behavior at the novel site was habituated, indicating that the induced behavioral facilitation did not generalize throughout the animal, as normally occurs during sensitization, but was limited to a single stimulus–response pathway.     

Sensitization as a mechanism for multiple chemical sensitivity: relationship to evolutionary theory

Multiple chemical sensitivity (MCS) is a disorder in humans attributed to prior chemical exposure. Sensitization is an amplification of neuronal responsiveness that elicits increased behavioral responding to stimuli, and occurs in a recently developed rat model of MCS. Rats were exposed to repeated formaldehyde (Form) and their response in three behavioral tests, including locomotor activity after a cocaine challenge, conditioned fear, and behavioral avoidance of Form, was assessed. In all three tests, rats demonstrated sensitized behaviors, implicating amplified responding within specific limbic brain regions. Evolutionary theory in the context of MCS specifies how the behavioral strategies of those with MCS are consistent with the notion that their self-perceived sense of survival and reproductive fitness may be threatened by chemical exposures. This behavior may be mediated by the same limbic brain regions that become sensitized after repeated chemical exposure in animals.     

Associative morphine tolerance in the rat: examinations of compensatory responding and cross-tolerance with stress-induced analgesia

The results of three experiments designed to examine the processes subserving associative tolerance to morphine's analgesic effects, as assessed by the tail-flick test, are reported. The experiments indicated that associative tolerance in male Holtzman rats was not subserved by conditioned compensatory responses but was cross-tolerant with an apparently nonopioid form of stress-induced analgesia (SIA). Experiment 1 showed that rats tested for morphine analgesia in a distinctive context that had been paired previously with morphine injections (5 mg/kg) were more tolerant than animals that had had this context explicitly unpaired with a series of morphine injections or animals that were drug-naive. There was no evidence of a conditioned compensatory response of hyperalgesia in animals given a saline injection in the presence of environmental stimuli that had been previously paired with morphine, even under test conditions designed to minimize the possibility of floor effects that might have obscured the detection of drug-compensatory hyperalgesia. Experiment 2 demonstrated that the footshock procedures used for stress induction produced an SIA that was not attenuated by naloxone (10 mg/kg). Experiment 3 replicated the associative tolerance phenomenon of Experiment 1 and again failed to find evidence of conditioned compensatory responses. It was found that animals exposed to footshock in the context that had been associated with morphine administration developed significantly less SIA than control animals. The relevance of these findings for associative models of drug tolerance is discussed.     

Kindling-induced changes in plasticity of the rat amygdala and hippocampus

Temporal lobe epilepsy (TLE) is often accompanied by interictal behavioral abnormalities, such as fear and memory impairment. To identify possible underlying substrates, we analyzed long-term synaptic plasticity in two relevant brain regions, the lateral amygdala (LA) and the CA1 region of the hippocampus, in the kindling model of epilepsy. Wistar rats were kindled through daily administration of brief electrical stimulations to the left basolateral nucleus of the amygdala. Field potential recordings were performed in slices obtained from kindled rats 48 h after the last induced seizure, and in slices from sham-implanted and nonimplanted controls. Kindling resulted in a significant impairment of long-term potentiation (LTP) in both the LA and the CA1, the magnitude of which was dependent on the number of prior stage V seizures. Saturation of CA1-LTP, assessed through repeated spaced delivery of high-frequency stimulation, occurred at lower levels in kindled compared to sham-implanted animals, consistent with the hypothesis of reduced capacity of further synaptic strengthening. Furthermore, theta pulse stimulation elicited long-term depression in the amygdala in nonimplanted and sham-implanted controls, whereas the same stimulation protocol stimulation caused LTP in kindled rats. In conclusion, kindling differentially affects the magnitude, saturation, and polarity of LTP in the CA1 and LA, respectively, most likely indicating an activity-dependent mechanism in the context of synaptic metaplasticity.     

Drug and environmentally induced manipulations of the opiate and serotonergic systems alter nociception in neonatal rat pups

The influence of drug- and environmentally induced alterations in serotonergic and opiate activity on pain sensitivity was assessed in 6-day-old Sprague-Dawley-derived rat pups using tail flick-testing procedures. The opiate agonist morphine was observed to induce tail flick analgesia that was blocked by concurrent administration of the opiate antagonist naloxone. Similarly, the serotonergic agonist quipazine induced analgesia that was blocked by pretreatment with the serotonergic antagonist metergoline. Naloxone alone did not alter tail flick responsivity in non-isolated, nondeprived neonates, suggesting that the opiate system may not exert a significant tonic inhibition of pain sensitivity in neonates. In contrast, the serotonergic system may exert some tonic analgesic influence at this age, given that metergoline was observed to induce slight hyperalgesia in nondeprived, non-isolated neonates. Twenty four hours of food and maternal deprivation, shown previously to increase brain serotonin and 5-hydroxyindole acetic acid and their ratio in neonates (L. P. Spear & F. M. Scalzo, 1984, Developmental Brain Research, in press) was observed to induce tail flick analgesia, an effect blocked by metergoline. Isolation from siblings and the dam and nest for 30 min also induced tail flick analgesia; this analgesia was blocked by treatment with naloxone prior to testing. Together, these experiments support the suggestion that the serotonergic and opiate systems may regulate pain sensitivity even in neonatal rat pups, with agonist- or environmentally precipitated increases in serotonergic or opiate activity inducing significant analgesia during the early postnatal period.     

Proactive behavior,but not inhibitory control,predicts repeated innovation by spotted hyenas tested with a multi-access box

Innovation is widely linked to cognitive ability, brain size, and adaptation to novel conditions. However, successful innovation appears to be influenced by both cognitive factors, such as inhibitory control, and non-cognitive behavioral traits. We used a multi-access box (MAB) paradigm to measure repeated innovation, the number of unique innovations learned across trials, by 10 captive spotted hyenas (Crocuta crocuta). Spotted hyenas are highly innovative in captivity and also display striking variation in behavioral traits, making them good model organisms for examining the relationship between innovation and other behavioral traits. We measured persistence, motor diversity, motivation, activity, efficiency, inhibitory control, and neophobia demonstrated by hyenas while interacting with the MAB. We also independently assessed inhibitory control with a detour cylinder task. Most hyenas were able to solve the MAB at least once, but only four hyenas satisfied learning criteria for all four possible solutions. Interestingly, neither measure of inhibitory control predicted repeated innovation. Instead, repeated innovation was predicted by a proactive syndrome of behavioral traits that included high persistence, high motor diversity, high activity and low neophobia. Our results suggest that this proactive behavioral syndrome may be more important than inhibitory control for successful innovation with the MAB by members of this species.     

Learned preferences induced by electrical stimulation of a food-related area of the parabrachial complex: effects of naloxone

Electrical stimulation of the External Lateral Parabrachial Subnucleus (LPBe), a food-related area, induced behavioral preferences for associated stimuli in a taste discrimination learning task. Although this stimulation appeared to be ineffective to elicit standard lever press self-stimulation, it induced place preference for one of two training compartments of a rectangular maze in which animals (adult male Wistar rats) received concurrent electrical brain stimulation. In subjects that consistently showed a preference behavior in different trials, administration of the opioid antagonist naloxone (4 mg/ml/kg) blocked concurrent learning when the test was made in a new maze but not in the same maze in which animals had learned the task. These results are discussed in terms of the possible participation of the LPBe subnucleus in different natural and artificial brain reward systems.     

第三方惩罚的神经机制：来自经颅直流电刺激的证据

第三方惩罚既是社会规范在群体得以维系的基石, 也是个体维护社会规范的体现。当前关注社会规范的神经研究大多基于第二方惩罚的独裁者或最后通牒实验框架, 缺乏对第三方维护社会规范过程中相关脑区活动的探索, 对这一过程的内在神经机制也不清楚。本文基于第三方惩罚的独裁者博弈框架, 对右侧背外侧前额叶区域(DLPFC)进行不同极性的经颅直流电刺激(tDCS), 同时依据第三方是否需要为其惩罚付出成本设计了零成本和有成本两个实验任务。结果发现, 第三方在零成本任务的情绪反应和惩罚显著受到tDCS设置的影响, 且阴极刺激显著提升了第三方的惩罚值, 这表明情绪机制对第三方惩罚有着重要影响。另外, 第三方在零成本和有成本任务中的惩罚差异在不同tDCS设置之间也存在显著差异, 这与第三方惩罚还受到自利机制影响的观点相符。本文率先为右侧DLPFC活动影响第三方惩罚提供了神经层面的证据, 且支持了第三方对社会规范的遵从与其负性情绪反应和自利加工密切相关的机制解释。     

Exposure to a stressor produces a long lasting enhancement of fear learning in rats

In contextual fear conditioning, footshock is given in a context, and re-exposure to this context elicits the conditional defensive response of freezing, a reliable behavioral index of conditional fear. Normally, the amount of contextual freezing is directly proportional to the number of shocks an animal receives in the context. However, pre-exposure to a stressor can produce an enhancement in conditional freezing. Pre-exposure to repeated footshock in one context produces an enhancement of conditional freezing to cues associated with a single shock in a second distinct context. This model of stress-enhanced fear learning (SEFL) can be utilized to study how stress affects learning of future aversive events. The experiments in this paper characterize the magnitude and longevity of SEFL. In the first experiment, the number of footshocks given during the pre-exposure session was varied and conditional fear to the single shock was assessed. Pre-exposure to 1 shock did not produce an enhancement in fear learning in the second context, but pre-exposure to 4 or 15 shocks did. The time-course of the enhancement was examined in the next two experiments. These experiments show that SEFL persists for at least 3 months.     

Goal-driven attentional capture by invisible colors: Evidence from event-related potentials

We combined event-related brain potentials (ERPs) and behavioral measures to test whether subliminal visual stimuli can capture attention in a goal-dependent manner. Participants searched for visual targets defined by a specific color. Search displays served as metacontrast masks for preceding cue displays that contained one cue in the target color. Although this target-color cue was spatially uninformative, it produced behavioral spatial cuing effects and triggered an ERP correlate of attentional selection (i.e., the N2pc component). These results demonstrate that target-color cues captured attention, in spite of the fact that cue localization performance assessed in separate blocks was at chance level. We conclude that task-set contingent attentional capture is not restricted to supraliminal stimuli, but is also elicited by visual events that are not consciously perceived.     

Homeostatic theory of drug tolerance: a general model of physiological adaptation

At the heart of homeostatic theory is the idea that explicit or implicit behavioral demands placed on physiological systems are required for the biological detection of homeostatic disturbances. The detection of drug-induced disturbances is required to drive the development of all systemic tolerance, both associative and nonassociative (i.e., both forms of tolerance are behaviorally contingent). A wide range of findings ranging from morphine-induced analgesia to ethanol-induced hyposexuality shows that contingent tolerance is pervasive and may be universal. The theory also stipulates that behavioral demands placed on the target system will govern the loss of both associative and nonassociative tolerance (physiological). The present formulation integrates contingent, associative, and nonassociative tolerance and drug-opposite withdrawal reactions within a unified theory.     

Behavioral detection of subcortical stimuli: comparison of somatosensory and "motor" circuits

Cats were trained to press a lever for food reinforcement in response to stimulation of the ventral lateral (VL) nucleus of the thalamus and the deep cerebellar nuclei. By scaling stimulus intensities relative to the appearance of a minimal amplitude evoked response in pericruciate cortex, it was possible to measure behavioral detection thresholds and correlate behavior with electrocortical activity. With stimulus rates of 25 Hz or greater, VL was the least effective stimulus site for producing detection. At stimulus rates less than 25 Hz, stimulation of the lateral or interpositus nuclei was even less effective in eliciting behavior, but at rates of 25 Hz or more, detection thresholds decreased below those for VL stimulation; cerebellar stimulation produced detection as readily as had stimulation of the ventrobasal complex in other experiments. These findings suggest that the cerebellum may modulate sensory experiences and that some portions of cerebral cortex, the pericruciate and suprasylvian regions, do not appear to be directly involved in mediating sensory detection. It is postulated that the neural detection circuits are more likely to be found in subcortical than in cerebrocortical structures.     

Medial preoptic area/anterior hypothalamus and sexual motivation

The medial preoptic area/anterior hypothalamus (MPOA/AH) is a brain site derived from proliferative zones from the diencephalon and telencephalon. It is probably this characteristic that makes this brain region participate in different physiological and behavioral functions. The present review addresses the role of the MPOA/AH in the control of male sexual behavior. It is clear that the MPOA/AH is a crucial site in the control of sexual behavior in males of all species studied to date. But although many different publications have followed the contribution of Heimer and Larsson there is no agreement as to what is specifically the role of the MPOA/AH in sexual behavior. At least three hypotheses have been presented. The first one suggests that this brain region is involved in the consummatory aspects (execution) of sexual behavior. The second indicates that the MPOA/AH is involved in the appetitive components (motivation) of masculine sexual behavior. The third hypothesis considers that MPOA/AH neurons are involved in the regulation of consummatory and appetitive aspects of sexual behavior. From the literature reviewed, it will become evident that the evidence supporting a role of the MPOA/AH in the execution of sexual behavior is based on a number of limited studies not easy to interpret. On the other hand, several lines of evidence using a variety of methodologies support the notion that the MPOA/AH is involved in the motivational aspects of male sexual behavior.     

Cardiac and behavioral responses to rocking stimulations in one- and three-month-old infants

Cardiac and behavioral reactions to lateral rocking stimulations were analysed at two different ages (1 and 3 months) and at two speeds of motion for the younger infants. Sixteen 1- and 3-mo.-old infants received 12 10-sec. trials of four complete cycles of vestibulokinesthetic stimulation (rapid rocking) and another group of 10 1-mo.-olds received one complete cycle in the same time period (slow rocking) provided by a motorized cradle. Stimulations were given when infants were in an alert state. Rapid and slow rocking induced similar cardiac responses in younger infants; these responses varied according to the type of motor reaction observed at stimulus onset. Cardiac acceleration was shown with motor activation and cardiac deceleration with motor quieting. In 3-mo.-olds, cardiac deceleration appeared with both types of motor reaction. A strong link between cardiac and behavioral responses in younger infants may prevent the occurrence of the usual simple cardiac index of orienting (heart-rate deceleration). In older infants, cardiac deceleration to rocking stimulation appeared even when it produced concomitant behavioral arousal. Vestibulokinesthetic stimulation is interpreted as having an important homeostatic effect on the young organism.     

Observational learning in mice can be prevented by medial prefrontal cortex stimulation and enhanced by nucleus accumbens stimulation

The neural structures involved in ongoing appetitive and/or observational learning behaviors remain largely unknown. Operant conditioning and observational learning were evoked and recorded in a modified Skinner box provided with an on-line video recording system. Mice improved their acquisition of a simple operant conditioning task by observational learning. Electrical stimulation of the observer's medial prefrontal cortex (mPFC) at a key moment of the demonstration (when the demonstrator presses a lever in order to obtain a reward) cancels out the benefits of observation. In contrast, electrical stimulation of the observer's nucleus accumbens (NAc) enhances observational learning. Ongoing cognitive processes in the demonstrator could also be driven by electrical stimulation of these two structures, preventing the proper execution of the ongoing instrumental task (mPFC) or stopping pellet intake (NAc). Long-term potentiation (LTP) evoked in these two cortical structures did not prevent the acquisition or retrieval process--namely, mPFC and/or NAc stimulation only prevented, or modified, the ongoing behavioral process. The dorsal hippocampus was not involved in either of these two behavioral processes. Thus, both ongoing observational learning and performance of an instrumental task require the active contribution of the mPFC and/or the NAc.     

Brain-stimulation intensity, rate of self-stimulation, and reinforcement strength: an analysis through chaining

Reinforcement strengths of different intensities of brain stimulation were assessed by means of a two-member behavioral chain. A variable interval schedule of 30 sec was the first-member, and five lever presses, each rewarded with stimulation, was the second. It was found that response rate on the VI schedule continued to increase beyond the intensity value which produced peak rate on the second-member, self-stimulation lever. It was concluded (1) that brain-stimulation reinforcement strength cannot be assessed adequately by means of self-stimulation rate, and (2) the chaining technique employed in the present experiment appears promising as an analytical tool in brain-stimulation research. Finally, some aspects of the data suggested a fatigue or stimulation-adaptation phenomenon.     

疼痛表征在自我和他人间的一致性效应

在以往研究中“pain matrix”被认为是加工自我和他人疼痛信息的特异性神经机制, 也可能是个体对他人疼痛共情的原因。但是最近的研究发现非疼痛的感觉刺激也能激活该脑区, 因此疼痛表征在自我和他人间是否存在一致性受到质疑。研究采用启动范式从两个方面入手探索自身疼痛和疼痛共情间是否存在一致性关系。实验一使用疼痛和非疼痛图片为启动刺激, 疼痛或热刺激为靶刺激, 发现相对于非疼痛图片, 疼痛图片启动下被试对自身疼痛刺激的反应时减少, 疼痛水平和情绪反应增强。实验二使用疼痛和热刺激为启动刺激, 疼痛或非疼痛图片为靶刺激, 发现相对于热刺激, 疼痛刺激启动下被试对疼痛图片的反应时减少。同时, 在两个实验中非疼痛的靶刺激都不受启动刺激的影响。这说明疼痛表征在自我和他人间存在一致性效应。     

Visual aspects of centrally elicited attack behavior in the cat: “Patterned reflexes” associated with selection of and approach to a rat

It has been previously suggested that the electrical brain stimulation which elicits quiet-biting attack in the cat actively affects the way the central nervous system processes visual and tactile information concerned with the reflexes involved in the terminal aspects of attack. In order to examine the effects of brain stimulation on a nonterminal aspect of attack – the stimulated cat's selection of and approach to a rat – cats were implanted with attack-eliciting electrodes in both the lateral hypothalamus and the midbrain ventral tegmental area. These cats were then tested in an 8-ft-long cage, one end of which was divided into three, 2-ft-long parallel compartments, whose openings faced the end of the cage from which the cat commenced its approach. An anesthetized rat was placed at the back of one compartment, a bowl of food at the back of another compartment, and the third compartment contained no object. It was found in the first experiment that the attack elicited by nearly all electrodes was selectively directed at the rat. However, the success of the cat in finding the compartment containing the rat varied dramatically for different electrodes in the same cat. Further, these differences were stable and did not change as the cat gained experience with the task. The results suggested that the stimulation of different brain sites in the same cat differentially affected the visual neural mechanisms involved in guiding a cat to a rat. Previous studies have also suggested that the effects of brain stimulation which elicits quiet-biting attack are largely lateralized to the side of the brain stimulated. In order to determine if the effects of stimulation on the neural mechanisms mediating the visually guided approach of a cat to a rat were also lateralized, attempts were made in a second experiment to disrupt the visual input to one side of the brain by unilaterally transecting the optic tract. It was found that this manipulation interfered with the visually guided selective approach to a rat, if the cat was stimulated through hypothalamic or mid-brain electrodes ipsilateral to the optic tract transection, but not if the hypothalamic or midbrain stimulation was on the contralateral (visually intact) side of the brain. However, any final interpretation of the results was confounded by the finding in all of these cats of a complex syndrome of neglect of all contralateral sensory information.     

Brain stimulation techniques in the treatment of obsessive-compulsive disorder: current and future directions

Recent studies on the epidemiology of obsessive-compulsive disorder (OCD) estimate 50 million patients suffer from OCD worldwide, thus making it a global problem. The treatment of OCD has changed substantially over the last 2 decades following the introduction of selective serotonin reuptake inhibitors, which provide symptom improvement in approximately 60% of patients. However, some patients remain resistant to the standard pharmacologic and behavioral treatments. Although some treatment-resistant patients respond to pharmacologic augmentations, others do not, and there is evidence that some of the most severe cases benefit from treatment with neurosurgical interventions. Besides pharmacologic, behavioral, and neurosurgical approaches, different brain stimulation methods-transcranial magnetic stimulation, deep brain stimulation, and electroconvulsive therapy-have been investigated in treatment-resistant patients with OCD. However, available data about the use of these techniques in OCD treatment are quite limited in terms of sample size and study design, given the difficulty in conducting standard blinded trials for these procedures. In addition, none of the mentioned treatments have received Food and Drug Administration approval for the treatment of OCD. Nevertheless, promising findings regarding efficacy, tolerability, and non-invasiveness and/or reversibility of these techniques have increased interest in investigating their use in treatment-resistant OCD.     

Lateral differences in habituation of ipsilateral head-turning to repeated tactile stimulation in the human newborn

Lateral differences in habituation of ipsilateral head-turning to repeated tactile perioral stimulation following midline head restriction was studied in 44 full-term neonates. Left-sided stimulation had a significantly greater and faster decremental effect than right-sided stimulation. Even in the absence of tactile stimulation (Control Group), head-turning to the left decreased systematically whereas head-turning to the right did not. The transient efficacy of prior midline head restriction for the elimination of lateral differences in both spontaneous head movements and responsiveness to tactile input suggests that behavioral asymmetry is already well-established in the newborn.