Neural correlates of Pavlovian conditioning in components of the neural network supporting ciliary locomotion in Hermissenda

Pavlovian conditioning in Hermissenda consists of pairing light, the conditioned stimulus (CS) with activation of statocyst hair cells, the unconditioned stimulus (US). Conditioning produces CS-elicited foot shortening and inhibition of light-elicited locomotion, the two conditioned responses (CRs). Conditioning correlates have been identified in the primary sensory neurons (photoreceptors) of the CS pathway, interneurons that receive monosynaptic input from identified photoreceptors, and putative pedal motor neurons. While cellular mechanisms of acquisition produced by the synaptic interaction between the CS and US pathways are well-documented, little is known about the mechanisms responsible for the generation or expression of the CR. Here we show that in conditioned animals light reduced tonic firing of ciliary activating pedal neurons (VP1) below their pre-CS baseline levels. In contrast, pseudorandom controls expressed a significant increase in CS-elicited tonic firing of VP1 as compared to pre-CS baseline activity. Identified interneurons in the visual pathway that have established polysynaptic connections with VP1 were examined in conditioned animals and pseudorandom controls. Depolarization of identified type I_e interneurons with extrinsic current elicited a significant increase in IPSPs recorded in VP1 pedal neurons of conditioned animals as compared with pseudorandom controls. Conditioning also enhanced intrinsic excitability of type I_e interneurons of conditioned animals as compared to pseudorandom controls. Light evoked a modest increase in IPSP frequency in VP1 of conditioned preparations and a significant decrease in IPSP frequency in VP1 of pseudorandom controls. Our results show that a combination of synaptic facilitation and intrinsic enhanced excitability in identified components of the CS pathway may explain light-elicited inhibition of locomotion in conditioned animals.     

The coding of roughness.

This review examines the way information about textures is captured, encoded, and processed by the somatosensory system to produce sensations of roughness/smoothness. Textures with spatial periods exceeding about 200 microm are encoded spatially, so roughness is nearly independent of the speed and direction of their movement across the skin. The information consists of spatial variations in activity among slowly adapting (SA1) mechanoreceptors, and appears to be extracted by specialized cortical neurons. Perception of the roughness of finer surfaces is mediated by detection, primarily by Pacinian afferents, of cutaneous vibrations generated when textures move across the skin. Movement is necessary to the perception of these textures, and vibrotactile adaptation interferes with it. The code is an intensitive one (i.e., the amount of activity in Pacinian afferents).     

Ghrelin stimulates corticotropin-releasing factor and vasopressin gene expression in rat hypothalamic 4B cells

Corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) play a central role in regulating the stress response. In response to stress, CRF and AVP neurons in the hypothalamic paraventricular nucleus secrete the peptides to stimulate the release of adrenocorticotropic hormone from the anterior pituitary. Ghrelin, an endogenous ligand of the growth hormone-releasing peptide receptors (GHSR), has been shown to stimulate the release of CRF and AVP by rat hypothalamic explants. However, little is known about the ability of the ghrelin signaling pathways to activate the CRF and AVP genes in the hypothalamus. In the present study, we examined the direct effect of ghrelin on CRF and AVP gene expression in hypothalamic 4B cells, which show the characteristics of the hypothalamic parvocellular paraventricular nucleus neurons. Cells were transfected with CRF or AVP promoter to examine the activity of each promoter. Ghrelin stimulated the promoter activities and mRNA levels for both CRF and AVP. The involvement of a protein kinase pathway was examined using inhibitors. Protein kinase A and phospholipase C pathways were shown to be involved in ghrelin-induced increases in both CRF and AVP promoter activities. GHSR type 1a (GHSR1a) mRNA levels were also increased by ghrelin, and these ghrelin-induced levels were suppressed by a GHSR1a antagonist. Thus, ghrelin-dependent pathways are involved in the regulation of CRF and AVP gene expression in the hypothalamus: ghrelin, an orexigenic hormone, stimulates CRF, an anorexigenic/anxiogenic factor in the hypothalamus, resulting in hypothalamic-pituitary-adrenal axis activation to stimulate the release of glucocorticoids.     

Discriminative touch and emotional touch.

Somatic sensation comprises four main modalities, each relaying tactile, thermal, painful, or pruritic (itch) information to the central nervous system. These input channels can be further classified as subserving a sensory function of spatial and temporal localization, discrimination, and provision of essential information for controlling and guiding exploratory tactile behaviours, and an affective function that is widely recognized as providing the afferent neural input driving the subjective experience of pain, but not so widely recognized as also providing the subjective experience of affiliative or emotional somatic pleasure of touch. The discriminative properties of tactile sensation are mediated by a class of fast-conducting myelinated peripheral nerve fibres--A-beta fibres--whereas the rewarding, emotional properties of touch are hypothesized to be mediated by a class of unmyelinated peripheral nerve fibres--CT afferents (C tactile)--that have biophysical, electrophysiological, neurobiological, and anatomical properties that drive the temporally delayed emotional somatic system. CT afferents have not been found in the glabrous skin of the hand in spite of numerous electrophysiological explorations of this area. Hence, it seems reasonable to conclude that they are lacking in the glabrous skin. A full understanding of the behavioural and affective consequences of the differential innervation of CT afferents awaits a fuller understanding of their function.     

The Organization of Extrinsic Neurons and Their Implications in the Functional Roles of the Mushroom Bodies in Drosophila melanogaster Meigen

Although the importance of the Drosophila mushroom body in olfactory learning and memory has been stressed, virtually nothing is known about the brain regions to which it is connected. Using Golgi and GAL4–UAS techniques, we performed the first systematic attempt to reveal the anatomy of its extrinsic neurons. A novel presynaptic reporter construct, UAS-neuronal synaptobrevin–green fluorescent protein (n-syb–GFP), was used to reveal the direction of information in the GAL4-labeled neurons. Our results showed that the main target of the output neurons from the mushroom body lobes is the anterior part of the inferior medial, superior medial, and superior lateral protocerebrum. The lobes also receive afferents from these neuropils. The lack of major output projections directly to the deutocerebrum’s premotor pathways discourages the view that the role of the mushroom body may be that of an immediate modifier of behavior. Our data, as well as a critical evaluation of the literature, suggest that the mushroom body may not by itself be a “center” for learning and memory, but that it can equally be considered as a preprocessor of olfactory signals en route to “higher” protocerebral regions.     

Bidirectional plasticity in striatonigral synapses: a switch to balance direct and indirect basal ganglia pathways

There is no hypothesis to explain how direct and indirect basal ganglia (BG) pathways interact to reach a balance during the learning of motor procedures. Both pathways converge in the substantia nigra pars reticulata (SNr) carrying the result of striatal processing. Unfortunately, the mechanisms that regulate synaptic plasticity in striatonigral (direct pathway) synapses are not known. Here, we used electrophysiological techniques to describe dopamine D(1)-receptor-mediated facilitation in striatonigral synapses in the context of its interaction with glutamatergic inputs, probably coming from the subthalamic nucleus (STN) (indirect pathway) and describe a striatonigral cannabinoid-dependent long-term synaptic depression (LTD). It is shown that striatonigral afferents exhibit D(1)-receptor-mediated facilitation of synaptic transmission when NMDA receptors are inactive, a phenomenon that changes to cannabinoid-dependent LTD when NMDA receptors are active. This interaction makes SNr neurons become coincidence-detector switching ports: When inactive, NMDA receptors lead to a dopamine-dependent enhancement of direct pathway output, theoretically facilitating movement. When active, NMDA receptors result in LTD of the same synapses, thus decreasing movement. We propose that SNr neurons, working as logical gates, tune the motor system to establish a balance between both BG pathways, enabling the system to choose appropriate synergies for movement learning and postural support.     

Enhanced involvement of brain vasopressin V1 receptors in cardiovascular responses to stress in rats with myocardial infarction

Stress is one of the factors provoking cardiovascular complications. The purpose of the study was to explore the role of vasopressin (VP) in central control of arterial blood pressure and heart rate under resting conditions and during stimulation by an alarming stress (air jet stress) in myocardial infarct-induced cardiac failure. Six groups of male Sprague Dawley (SD) rats were subjected either to sham surgery (sham rats) or to ligation of a left coronary artery (infarcted rats). After 5 weeks both infarcted and sham rats were subjected either to intracerebroventricular infusion of artificial cerebrospinal fluid (aCSF) (sham aCSF and infarcted aCSF), [Arg8]-VP (sham VP and infarcted VP) or VP V1a receptor antagonist (d(CH2)5[Tyr(Me)2Ala-]VP, sham V1ANT and infarcted V1ANT). Air jet stress elicited significantly greater increases in mean arterial blood pressure (MABP) and heart rate in the infarcted aCSF than in the sham aCSF rats. Intracerebroventricular infusion of V1ANT significantly reduced resting MABP and MABP and heart rate increases in response to stress in the infarcted but not in the sham rats. Intracerebroventricular infusion of VP elicited a significant increase in resting MABP in the infarcted VP but not in the sham VP rats. The results provide evidence for enhanced engagement of the brain V1 VP receptors in regulation of resting MABP and in generation of exaggerated cardiovascular responses to air jet stress during the post-infarct state.     

Distortions of vision and pain: two functional facets of D-lysergic acid diethylamide.

D-lysergic acid diethylamide (LSD) produces distortions of visual perception and analgesia. Evidence is advanced from a functional standpoint that the observed visual effects result from an attenuation of light-evoked input to the dorsal lateral geniculate nucleus (LGN) from the purely centripetal pathways of the retina. More slowly responding visual afferents or those with more complex receptive fields seem to be affected most. LSD analgesia, accompanied by severe psychotic symptoms, appears to result from drug actions on a centrifugally controlled pain system involving neurons of the midbrain raphe.     

吸烟:促进还是损害前瞻记忆?

以往研究对吸烟或尼古丁摄入影响前瞻记忆的特点和机制进行了探讨,发现吸烟或尼古丁摄入对前瞻记忆的影响具有双重机制:尼古丁能短暂刺激神经递质释放,并通过促进策略加工提高即时的前瞻记忆表现;但长期来看,吸烟会损伤心脑血管和神经元,降低认知和执行功能的水平,从而持久损害前瞻记忆。将来的研究应在区分前瞻记忆任务类型、尼古丁摄入方式等的基础上,进一步明确吸烟或尼古丁摄入影响前瞻记忆的机制。     

The biochemical bases of the placebo effect

A great variety of medical conditions are subject to the placebo effect. Although there is mounting evidence to suggest that the placebo effect is related to the expectation of clinical benefit, little is still known about the biochemical bases underlying placebo responses. Positron emission tomography studies have recently shown that the placebo effect in Parkinson’s disease, pain, and depression is related to the activation of the limbic circuitry. The observation that placebo administration induces the release of dopamine in the ventral striatum of patients with Parkinson’s disease suggests a link between the placebo effect and reward mechanisms. In addition to Parkinson’s disease, the placebo-reward model may also apply to other disorders. However, the relative contribution of the different neurotransmitters and neuropeptides that are known to be involved in modulating the activity of the limbic system may be disease-specific. Thus, while the placebo-induced clinical benefit observed in Parkinson’s disease would mostly reflect the release of dopamine in the dorsal striatum, the activation of opioid and serotonin pathways could be particularly implicated in mediating placebo responses encountered in pain and depression, respectively. An earlier version of this paper was presented at an international conference, “Placebo: Its Action and Place in Health Research Today,” held in Warsaw, Poland on 12–13 April, 2003.     

Blood pressure and pulse wave velocity measurement for operant conditioning of autonomic responding

Presently available procedures for measuring blood pressure are not completely satisfactory for Es wishing to investigate the operant conditioning of cardiovascular activity. A system is described for measuring a correlate of the blood pressure information obtained with conventional sphygmomanometric systems. The procedure involves the measurement of speed of propagation through the arterial system of the pressure pulse from the heart’s contraction. This speed, the pulse wave velocity, is closely related to cuff-derived blood pressure. Many of the problems present with current sphygmomanometric systems are absent with this apparatus and procedure. The apparatus can be assembled from common instruments or constructed from integrated circuits. Data collected with the apparatus confirm earlier studies which indicate that pulse wave velocity is correlated with sphygmomanometrically measured blood pressure and is a valuable cardiovascular response measure.     

Experimenting With Perceptual Change Strategies

Nonmetric multidimensional scaling procedures are employed in this experimental evaluation of perceptual changes resulting from differences in the presentation of information about stimuli. Longitudinal MDS techniques are found to be useful in monitoring perceptual changes produced by various communication alternatives. Communication strategies aimed at changing the relationships among stimuli are more effective than those designed to change the perceptual space structure. Furthermore, providing comparative information about groups of stimuli has more apparent impact than providing information about a single stimulus.     

Chemical plasticity of visual cortical neurons in integrative organization of feeding behavior in cats

The P.K. Anokhin conception of organization of systemic behavior was used to study the discharge activity and chemical plasticity of cortical neurons in a goal-directed behavior. Chemical sensitivity of neurons in the visual cortex of instrumentally conditioned cats was studied during successive stages of food procuring and consuming. The results showed that definite stages of this integrated behavioral act are characterized by differences in the chemical sensitivity of visual neurons to neurotransmitters. The largest number of neurons resistant to neurotransmitters was found among cells that did not respond at successive stages of goal-directed behavior. The iontophoretic delivery of cycloheximide and lyzilvasopressine altered the discharge activity of individual cortical neurons at different stages of stereotyped instrumental conditioned acts. This suggests that the integrative organization of the feeding behavior is determined by chemical plasticity of the brain’s visual cortical neurons and is dependent upon the processes of protein synthesis. According to the functional system theory (Anokhin, 1974) each brain neuron is included, by various degrees of freedom, in the stages of systemic organization that underlie the goal-directed behavior. Thanks to the plastic reorganization of brain units, each stage is directed toward the achievement of useful adaptive results for the organism during interaction with different environmental factors (Adrianov, 1993; Fadeev, 1988). It may be proposed that the reorganization of discharges of brain neurons that occurs at different stages of activity is due to changes in their chemical capacities. In concordance with such a hypothesis, the purpose of the present investigation was to study the chemical sensitivity of single visual cortical neurons to neurotransmitters at different stages of systemic organization of feeding behavior. The influence of protein synthesis inhibitors on the sensitivity of cortical neurons was also investigated.     

The recognition of mental states from dynamic and static facial expressions

The ability to recognize mental states from facial expressions is essential for effective social interaction. However, previous investigations of mental state recognition have used only static faces so the benefit of dynamic information for recognizing mental states remains to be determined. Experiment 1 found that dynamic faces produced higher levels of recognition accuracy than static faces, suggesting that the additional information contained within dynamic faces can facilitate mental state recognition. Experiment 2 explored the facial regions that are important for providing dynamic information in mental state displays. This involved using a new technique to freeze motion in a particular facial region (eyes, nose, mouth) so that this region was static while the remainder of the face was naturally moving. Findings showed that dynamic information in the eyes and the mouth was important and the region of influence depended on the mental state. Processes involved in mental state recognition are discussed.     

Implications of the cAMP signaling pathway in psychiatric disorders: a systematic review of the evidence

The last decade has seen a shift in the theoretical framework addressing the pathophysiology of psychiatric disorders. During this period, research endeavors have been directed toward investigating the biochemical mechanisms involved in the transduction of information from the cell surface to the cell interior. The emerging picture, supported by growing evidence, is that in addition to neurotransmitters and their receptors, various signal transduction pathways may be linked to the pathophysiology of major psychiatric disorders. In this review, the role of one such pathway--the cyclic adenosine monophosphate (cAMP) signaling pathway--will be highlighted. We review data suggesting the involvement of the upstream and downstream components of this system in the pathophysiology of psychiatric disorders.     

记忆过程中海马CA1区神经元的集群放电特征

观察空间工作记忆过程中海马CA1区神经元群的放电特征。应用多通道神经元集群放电记录技术, 同步观察和记录清醒大鼠在执行延迟选择任务时的行为轨迹以及海马CA1区神经元的放电活动。发现：海马CA1区位置细胞的位置野是在学习过程中逐渐形成并可消退; 部分位置细胞的放电对未来目标定向性行为具有预测作用; 在空间工作记忆过程中, 神经元放电之间的相关性加强, 神经元之间以及神经元与局部场电位之间存在相位编码方式。结果提示海马CA1区神经元参与对空间信息的初级编码和加工, 并为未来行为决策提供有效信息, 而且海马对信息的加工是通过局部神经网络进行, 时间编码可能是海马信息加工的重要方式之一。     

Differential sensitisation to central cardiovascular effects of angiotensin II in rats with a myocardial infarct: relevance to stress and interaction with vasopressin

The purpose of the present study was to elucidate if rats with myocardial infarction manifest altered responsiveness to central cardiovascular effects of low doses of angiotensin II (ANG II), and if ANG II and vasopressin (VP) cooperate in the central regulation of cardiovascular functions at rest and during stress. Conscious Sprague-Dawley rats with myocardial infarction induced by left coronary artery ligation, or sham-ligated (SL) controls were infused intracerebroventricularly with artificial cerebrospinal fluid (aCSF), ANG II, ANG II + VP or ANG II + V1a receptor antagonist (V1ANT) 4 weeks after cardiac surgery. In the infarcted but not in the SL rats, the resting mean arterial blood pressure (MABP) was significantly elevated by infusions of ANG II and ANG II + VP, while infusion of ANG II + V1ANT was not effective. During administration of aCSF, the pressor, and tachycardic responses to an air-jet stressor were significantly greater in the infarcted than in the SL rats. In the SL rats, the pressor responses to the stressor were significantly greater during infusions of ANG II, ANG II + VP and ANG II + V1ANT than during infusion of aCSF. The tachycardic response in the SL rats was enhanced only by the combined infusion of ANG II + VP. In the infarcted rats, the pressor and the tachycardic responses to the stressor were similar in all groups. It is concluded that: (1) under resting conditions the infarcted rats manifest sensitisation to the central pressor effect of ANG II and that this effect depends on concomitant stimulation of V1a VP receptors, (2) central ANG II may enhance the pressor response to an alarming stressor in the SL rats through an action which does not depend on the concomitant stimulation of V1a receptors, (3) the cooperative action of ANG II and VP is required for intensification of the tachycardic response to the alarming stressor in the SL rats and (4) exaggeration of the cardiovascular responses to the alarming stressor in the infarcted rats cannot be further augmented by an additional stimulation of central ANG II receptors or combined stimulation of ANG II and VP receptors.     

Domain specificity in the primate prefrontal cortex

Experimental studies in nonhuman primates and functional imaging studies in humans have underlined the critical role played by the prefrontal cortex (PFC) in working memory. However, the precise organization of the frontal lobes with respect to the different types of information operated upon is a point of controversy, and several models of functional organizations have been proposed. One model, developed by Goldman-Rakic and colleagues, postulates a modular organization of working memory based on the type of information processing (the domain specificity hypothesis). Evidence to date has focused on the encoding of the locations of visual objects by the dorsolateral PFC, whereas the ventrolateral PFC is suggested to be involved in processing the features and identity of objects. In this model, domain should refer to any sensory modality that registers information relevant to that domain—for example, there would be visual and auditory input to a spatial information processing region and a feature analysis system. In support of this model, recent studies have described pathways from the posterior and anterior auditory association cortex that target dorsolateral spatial-processing regions and ventrolateral object-processing regions, respectively. In addition, physiological recordings from the ventrolateral PFC indicate that some cells in this region are responsive to the features of complex sounds. Finally, recordings in adjacent ventrolateral prefrontal regions have shown that the features of somatosensory stimuli can be discriminated and encoded by ventrolateral prefrontal neurons. These discoveries argue that two domains, differing with respect to the type of information being processed, and not with respect to the sensory modality of the information, are specifically localized to discrete regions of the PFC and embody the domain specificity hypothesis, first proposed by Patricia Goldman-Rakic.