Subcellular interactions between parallel fibre and climbing fibre signals in purkinje cells predict sensitivity of classical conditioning to interstimulus interval

Classical conditioning of the nictitating membrane response requires a specific temporal interval between conditioned stimulus and unconditioned stimulus, and produces an incrase in Protein Kinase C (PKC) activation in Purkinje cells. To evaluate whether biochemical interactions within the Purkinje cell may explain the temporal sensitivity, a model of PKC activation byCa ²⁺, diacylglycerol (DAG), and arachidonic acid (AA) is developed.Ca ²⁺ elevation is due to CF stimulation and IP3 inducedCa ²⁺ release (IICR). DAG andIP ₃ result from PF stimulation, while AA results from phospholipase A2 (PLA ₂). Simulations predict increased PKC activation when PF stimulation precedes CF stimulation by 0.1 to 3 s. The sensitivity of IICR to the temporal relation between PF and CF stimulation, together with the buffering system of Purkinje cells, significantly contribute to the temporal sensitivity.     

Differential involvement of mGluR1 and mGluR5 in memory reconsolidation and retrieval in a passive avoidance task in 1-day old chicks

Group I metabotropic glutamate receptors (mGluRs) are involved in memory formation. The Ca2+ signal derived from stimulation of IP3 receptors (IP3Rs) via mGluRs, initiates protein synthesis that is required for memory consolidation and reconsolidation. However it has been suggested that different mechanisms are triggered by mGluR1/5 activation in these two processes. It is also not clear whether the transient amnesia observed after blockade of group I mGluRs after a reminder, results from disturbance of memory reconsolidation or temporal impairment of recall. The aim of this study was to examine more closely the role of mGluR1 in memory consolidation and reconsolidation and to detect differences in the participation of mGluR1 and mGluR5 in memory retrieval after initial training and after the remainder of the task. Our results demonstrate, that in chicks performing a one-trial passive avoidance task, antagonists of mGluR1, mGluR5 and IP3R significantly disturb memory consolidation and reconsolidation. Inhibition of mGluR5 and IP3R also impairs memory recall, whereas mGluR1 do not seem to participate in this process. The presented data suggest that activation of mGluR1 and mGluR5 is necessary for the correct course of memory consolidation and reconsolidation, whereas mGluR5 are additionally involved in retrieval processes dependent on Ca2+ release from IP3 activated intracellular stores.     

Effects of Paired and Unpaired Eye-Blink Conditioning on Purkinje Cell Morphology

This experiment addressed (1) the importance of conjunctive stimulus presentation for morphological plasticity of cerebellar Purkinje cells and inhibitory interneurons and (2) whether plasticity is restricted to the spiny branches of Purkinje cells, which receive parallel fiber input. These issues were investigated in naive rabbits and in rabbits that received paired or unpaired presentations of the conditioned stimulus (CS) and unconditioned stimulus (US). To direct CS input to the cerebellar cortex, pontine stimulation served as the CS. Air puffs to the cornea served as the US. Paired condition rabbits received pontine stimulation for 350 msec paired with a coterminating 100-msec air puff. Unpaired condition rabbits received the same stimuli in a pseudorandom order at 1- to 32-sec intervals. Rabbits were trained for a mean of 12 days. Naive rabbits received no treatment. In Golgi-stained Purkinje neurons in lobule HVI, total dendritic length, main branch length, total spiny branch length, and number of spiny branch arbors were all greater in the naive group than in the paired and unpaired groups, which did not differ. No differences were found between the hemispheres ipsilateral and contralateral to the trained eye. The dendritic length and number of branches for inhibitory interneurons did not differ across groups. The Purkinje cell morphological changes detected with these methods do not appear to be uniquely related to the conjunctive activation of the CS and US in the paired condition.     

Elaborative feedback: Engaging reward and task-relevant brain regions promotes learning in pseudoword reading aloud

Although much is known about the cognitive and neural basis of establishing letter-sound mappings in learning word forms, relatively little is known about what makes for the most effective feedback during this process. We sought to determine the neural basis by which elaborative feedback (EF), which contains both reward-related and content-specific information, may be more helpful than feedback containing only one kind of information (simple positive feedback, PF) or the other (content feedback, CF) in learning orthography-phonology (spelling-sound) mappings for novel letter strings. Compared to CF, EF activated the ventromedial prefrontal cortex, implicated in reward processing. Compared to PF, EF activated the posterior middle temporal, superior temporal, and supramarginal gyri—regions implicated in orthography-phonology conversion. In the same comparison, EF also activated the left fusiform gyrus/visual word form area—implicated in orthographic processing. Also EF, but not CF or PF, modulated activity in the caudate nucleus. In a postscan questionnaire, EF and PF were rated as more pleasant than CF, suggesting that modulation of the caudate for EF may be due to the coupling of reward and skill content. These findings suggest the enhanced effectiveness of EF may be due to concurrent activation of reward-related and task-relevant brain regions.     

Analysis of sequence-dependent interactions between transient calcium and transmitter stimuli in activating adenylyl cyclase in Aplysia: possible contribution to CS--US sequence requirement during conditioning

An important recent insight in a number of neurobiological systems is that during learning, individual dually regulated proteins with associative properties function as critical sites of stimulus convergence. During conditioning in Aplysia, the Ca2+ /calmodulin-sensitive adenylyl cyclase (AC) in mechanosensory neurons serves as a molecular site of interaction between Ca2+ and serotonin [5-hydroxytryptamine (5-HT)]-two signals that represent the CS and US in these cells. Conditioning requires that the CS and US be paired within a narrow time window and in the appropriate sequence. AC shows an analogous sequence preference: It is more effectively activated when a pulse of Ca2+ precedes a pulse of 5-HT than when the 5-HT precedes Ca2+. One mechanism that contributes to this sequence preference is that Ca2+/calmodulin binding to AC accelerates the rate of AC activation by receptor-Gs. We have identified two additional properties of AC activation that would cause pairing with Ca2+ preceding 5-HT to be more effective than simultaneous pairing or pairing with the reciprocal sequence: (1) Activation of Aplysia AC by a Ca2+ pulse rose with a delay compared with activation by a 5-HT pulse. (2) A late pulse of Ca2+, which arrived after 5-HT, acted, via calmodulin, to accelerate the decay of AC activation by receptor-Gs. Together, these activation properties of AC may contribute to the CS-US sequence requirement of classical conditioning.     

Acute restraint stress enhances calcium mobilization and proliferative response in splenic lymphocytes from mice

Calcium (Ca2+ ) plays an essential role in lymphocyte activation and maturation. Acute and chronic stress has been shown to modulate the lymphocyte immune response; but the relationship between cytosolic free Ca2+ concentration ([Ca2+ ]i) and the immune response in lymphocytes following exposure to stress has not been examined. In the present study, we investigated the effects of acute restraint stress on [Ca2+ ]i and the proliferation of splenic lymphocytes from mice. We observed that 2 h of restraint significantly increased plasma corticosterone levels in mice. On examining [Ca2+ ]i and the proliferation ex vivo of splenic lymphocytes isolated from restraint-stressed mice using fura-2 and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, respectively, we found that acute restraint stress caused a significant increase in resting [Ca2+ ]i and significantly enhanced the ability of concanavalin A (Con A; a T-cell-selective mitogen) to increase [Ca2+ ]i but not that of lipopolysaccharide (LPS; a B-cell-selective mitogen). In addition, acute restraint stress significantly enhanced Con A-stimulated but not LPS-stimulated lymphocyte proliferation. Overall, there was a positive correlation between [Ca2+ ]i and T-cell proliferation following acute restraint stress. The enhancements of [Ca2+ ]i and T-cell proliferation were completely suppressed by verapamil (a Ca2+ channel blocker). These results suggest that acute restraint stress enhances Con A-stimulated T-cell proliferation by increasing [Ca2+ ]i via stimulation of Ca2+ entry.     

发展性阅读障碍的视听时间敏感性缺陷及其脑神经机制

阅读是一个视听加工过程,阅读障碍的产生可能是过程中视听时间敏感性缺陷的结果。视听时间敏感性指个体对视觉和听觉刺激出现时间的感知能力,可通过同时性判断、时间顺序判断和视听整合考察。研究发现,阅读障碍者在这一能力上表现出行为和脑层面异常。而这些研究多是拼音文字背景,汉语文字下该领域研究相当少。未来需要丰富实验设计,扩大对汉语背景下视听时间敏感性研究,并以此开发干预手段,为阅读障碍的机制和治疗提供借鉴。     

Temporal and spatial effects in luminance discrimination

Luminance difference thresholds (ΔI) were obtained by a successive and a simultaneous method of presenting the stimuli Spatial and temporal separation between the fields was the independent variable while other variables as stimulus size, luminance, retinal area of stimulation and duration were kept constant ΔI was less for simultaneously presented stimuli than for successively presented stimuli This was related to spatial and temporal interaction effects such that the greater the spatial interaction between simultaneously presented fields, the greater the discriminability while the greater the temporal interaction between successively presented fields, the less the sensitivity to luminance differences. It was suggested that the basis of the luminance discrimination may be different under conditions of temporal interaction than under conditions of spatial interaction between the fields.     

Infants' intermodal perception of two levels of temporal structure in natural events

Infants' intermodal perception of two levels of temporal structure uniting the visual and acoustic stimulation from natural, complex events was investigated in four experiments. Films depicting a single object (single, large marble) and a compound object (group of smaller marbles) colliding against a surface in an erratic pattern were presented to infants between 3 and months of age using an intermodal preference and search method. These stimulus events portrayed two levels of invariant temporal structure: (a) temporal synchrony united the sights and sounds of object impact, and (b) temporal microstructure, the internal temporal structure of each impact sound and motion, specified the composition of the object (single vs. compound). Experiment 1 demonstrated that by 6 months infants detected a relation between the audible and visible stimulation from these events when both levels of invariant temporal structure guided their intermodal exploration. Experiment 2 revealed that by 6 months infants detected the bimodal temporal microstructure specifying object composition. They looked predominantly to the film whose natural soundtrack was played even though the motions of objects in both films were synchronized with the soundtrack. Experiment 3 assessed infants' sensitivity to temporal synchrony relations. Two films depicting objects of the same composition were presented while the motions of only one of them was synchronized with the appropriate soundtrack. Both 6-month-olds showed evidence of detecting temporal synchrony relations under some conditions. Experiment 4 examined how temporal synchrony and temporal microstructure interact in directing intermodal exploration. The natural soundtrack to one of the objects was played out-of-synchrony with the motions of both. In contrast with the results of Experiment 2, infants at 6 months showed no evidence of detecting a relationship between the film and its appropriate soundtrack. This suggests that the temporal asynchrony disrupted their detection of the temporal microstructure specifying object composition. Results of these studies support on invariant-detection view of the development of intermodal perception.     

Timing of Conditioned Responses Utilizing Electrical Stimulation in the Region of the Interpositus Nucleus as a CS

A large body of evidence indicates that the cerebellum is essential for the acquisition, retention, and expression of the standard delay conditioned eyeblink response and that the basic memory trace appears to be established in the anterior interpositus nucleus (IP). Adaptive timing of the conditioned response (CR) is a prominent feature of classical conditioning-the CR peaks at the time of onset of the unconditioned stimulus (US) over a wide range of CS-US interstimulus intervals (ISI). A key issue is whether this timing is established by the cerebellar circuitry or prior to the cerebellum. In this study timing of conditioned eyeblink responses established via electrical stimulation of the interpositus nucleus as a conditioned stimulus (CS) was analyzed prior to and following modification of the CS-US interval in well-trained rabbits. Consistent with previous results, learning under these conditions is very rapid and robust. The CR peak eyeblink latencies are initially timed to the US onset and adjust accordingly to lengthening or shortening of the CS-US interval, just as with peripheral CSs. The acquisition of conditioned eyeblink responses by direct electrical stimulation of the IP as a CS thus retains temporal flexibility following shifts in the CS-US delay, as found in standard classical eyeblink conditioning procedures.     

Timing of conditioned responses utilizing electrical stimulation in the region of the interpositus nucleus as a CS

A large body of evidence indicates that the cerebellum is essential for the acquisition, retention, and expression of the standard delay conditioned eyeblink response and that the basic memory trace appears to be established in the anterior interpositus nucleus (IP). Adaptive timing of the conditioned response (CR) is a prominent feature of classical conditioning—the CR peaks at the time of onset of the unconditioned stimulus (US) over a wide range of CS-US interstimulus intervals (ISI). A key issue is whether this timing is established by the cerebellar circuitry or prior to the cerebellum. In this study timing of conditioned eyeblink responses established via electrical stimulation of the interpositus nucleus as a conditioned stimulus (CS) was analyzed prior to and following modification of the CS-US interval in well-trained rabbits. Consistent with previous results, learning under these conditions is very rapid and robust. The CR peak eyeblink latencies are initially timed to the US onset and adjust accordingly to lengthening or shortening of the CS-US interval, just as with peripheral CSs. The acquisition of conditioned eyeblink responses by direct electrical stimulation of the IP as a CS thus retains temporal flexibility following shifts in the CS-US delay, as found in standard classical eyeblink conditioning procedures.     

Modification of the rat's acoustic startle response by antecedent visual stimulation.

Male hooded and albino rats were exposed to a light flash followed at various temporal intervals by a startle-eliciting 117 db. (re 20 muN/m2) burst of white noise. The visual stimulus engendered startle response inhibition (maximally when the lead time was 64-250 msec) as well as startle response latency reduction (maximally when the lead time was 2-8 msec). The temporal functions for the effects of visual stimuli paralleled those previously reported for startle modification by acoustic events. Further study revealed that, given optimal lead times, inhibition is produced reliably by weaker visual stimuli (3 X 10-6 cd-sec/cm2) than latency reduction (3 X 10-4 cd-sec/cm2). This differential sensitivity to visual stimuli is also analogous to previously reported findings for events in the acoustic environment. It reveals that the neural mechanisms that mediate latency reduction and inhibition can be engaged by either acoustic or visual stimulation.     

Excitatory and inhibitory learning with absent stimuli

Three experiments showed that 2 associatively activated stimulus representations may engage in excitatory or inhibitory learning, depending on their temporal relationship. Experiment 1a suggested that simultaneously activated stimulus representations show evidence of inhibitory learning in an acquisition test. Experiment 1b showed similar evidence of inhibition in a summation test. Experiment 2 found that activation of 2 stimulus representations in a serial compound resulted in excitatory learning between the antecedent and the subsequent (forward) and inhibitory learning between the subsequent and the antecedent (backward). The results show the dynamic influence of temporal contiguity on mediated learning.     

Stimulus and temporal cues in classical conditioning

In 2 experiments, separate groups of rats were given stimulus conditioning, temporal conditioning, untreated control and (in Experiment 2) learned irrelevance control procedures, followed by a compound with both stimulus and temporal cues. Stimulus conditioning consisted of a random 15-s duration conditioned stimulus (CS) followed by food; temporal conditioning consisted of food-food intervals of fixed 90 s (Experiment 1) or fixed 75 + random 15 s (Experiment 2). The stimulus group abruptly increased responding after CS onset, and the temporal group gradually increased responding over the food-food interval. When the food-food interval was fixed 90 s, the temporal cue exerted stronger control in the compound, whereas when the food-food interval was fixed 75 + random 15 s, the stimulus cue exerted stronger control. The strength of conditioning, temporal gradients of responding, and cue competition effects appear to reflect simultaneous timing of multiple intervals.     

Vibrotactile thresholds during background vibration of long duration

Thresholds for vibrotactile stimuli of low and high frequency (20 and 150 Hz) were determined during a long-lasting (15 min) background stimulus of low or high frequency (40 or 240 Hz). Thresholds for high frequency were markedly elevated during both low and high frequency background stimulation, whereas thresholds for low frequency were elevated only at the beginning of high-frequency background stimulation. The present results indicate that during activation of the high-frequency vibrotactile channel it is possible to find both a cross-channel and a channel specific inhibition depending on the temporal parameters of the background stimulus. The effects of the present low-frequency background stimulus can be explained on the basis of a minor co-activation of the high-frequency channel.     

The effects of voluntary movements on auditory-haptic and haptic-haptic temporal order judgments

In two experiments we investigated the effects of voluntary movements on temporal haptic perception. Measures of sensitivity (JND) and temporal alignment (PSS) were obtained from temporal order judgments made on intermodal auditory-haptic (Experiment 1) or intramodal haptic (Experiment 2) stimulus pairs under three movement conditions. In the baseline, static condition, the arm of the participants remained stationary. In the passive condition, the arm was displaced by a servo-controlled motorized device. In the active condition, the participants moved voluntarily. The auditory stimulus was a short, 500Hz tone presented over headphones and the haptic stimulus was a brief suprathreshold force pulse applied to the tip of the index finger orthogonally to the finger movement. Active movement did not significantly affect discrimination sensitivity on the auditory-haptic stimulus pairs, whereas it significantly improved sensitivity in the case of the haptic stimulus pair, demonstrating a key role for motor command information in temporal sensitivity in the haptic system. Points of subjective simultaneity were by-and-large coincident with physical simultaneity, with one striking exception in the passive condition with the auditory-haptic stimulus pair. In the latter case, the haptic stimulus had to be presented 45ms before the auditory stimulus in order to obtain subjective simultaneity. A model is proposed to explain the discrimination performance.     

Perceptual modification of sensitivity (d′): Modifying temporal resolution by the consistency of the spatial configuration

The major question in this study was whether perceptual modifications are basic alterations in a sensory system or changes in the S’s criterion. Four Ss were given prolonged training with a particular two-lined stimulus, deciding whether the stimulus had been presented in one continuous presentation or in two successive presentations with a temporal gap. The results confirmed the hypothesis, generated from modifications in visual cells, that the S’s sensitivity (d′) to a two-lined stimulus could be disrupted by the presentation of one original line with a new line. In contrast, two entirely new lines had little effect on the S’s sensitivity. A discussion of the results also indicated that temporal resolution must be a plastic process which depends on the consistency of the spatial configuration as well as temporal parameters.     

Depotentiation of vdccLTP Requires NMDAR Activation

Long-term potentiation is an enduring increase in synaptic efficacy following repeated stimulation of afferent fibers that is thought to underlie memory. In area CA1 of the hippocampus at least two forms of synaptic potentiation coexist at the same synapses; nmdaLTP and vdccLTP. NmdaLTP is induced by Ca2+ entry through NMDARs and is dependent on serine/threonine kinase activation, while vdccLTP is induced through Ca2+ entry through VDCCs and is dependent on tyrosine kinase activation. Depotentiation is a mechanism known to reverse nmdaLTP through phosphatase activation. The depotentiation of vdccLTP has not been previously investigated. We used hippocampal slices (area CA1) from male Long-Evans rats to induce vdccLTP with a 200-Hz tetanus in the presence of 50 microM APV. The 200-Hz tetanus resulted in a slowly developing vdccLTP that remained stable for at least 30 min. Thirty minutes after vdccLTP was induced, a low-frequency tetanus (3, 10, 20, 30, or 40 Hz) was applied in the presence of APV in an attempt to depotentiate vdccLTP. The 3- and 10-Hz low-frequency tetani resulted in no depotentiation. The 20- and 30-Hz tetani partially depotentiated vdccLTP (by approximately 13%), whereas the 40-Hz tetanus resulted in further potentiation. When APV was washed out prior to the 3-Hz low-frequency tetanus, the vdccLTP was completely depotentiated--presumably by NMDAR mechanisms. Our results indicate that vdccLTP is resistant to depotentiation under low-frequency stimulation conditions that readily depotentiate nmdaLTP. As tetanus frequencies are increased a small depotentiation is observed, suggesting that vdccLTP can be depotentiated to a small extent. When NMDARs are unblocked, vdccLTP can be completely depotentiated by a 3-Hz low-frequency tetanus, suggesting that vdccLTP can be depotentiated via activation of NMDAR mechanisms.     

TEMPORAL INTEGRATION OF PERCEPTUAL RESPONSE TO SUPRALIMINAL ELECTRICAL STIMULATION

E kman , G., F röberg , J. & F rankenhaeuser , M. Temporal integration of perceptual response to supraliminal electrical stimulation. Scand. J. Psychol ., 1968, 9, 83–88.—The effect of duration of electrical stimulation on perceived unpleasantness was investigated in 10 subjects. Duration of stimulation ranged from 0.05 to 3.00 sec. Three levels of intensity were investigated representing 2, 3, and 4 times the individual sensation threshold. For all stimulus intensities perceived unpleasantness was a simple logarithmic function of stimulus duration over the whole temporal range. This relation describes the trend of both the group data and the data from most individual subjects. The results support previous findings over a narrower temporal range and agree with results recently obtained in several additional sense modalities.     

Assimilation and contrast in perceptual judgments

An attempt is made to specify the differential conditions underlying two opposite context effects: assimilation and contrast. Assimilation occurs when the judgment of the current stimulus shifts in the direction of the preceding stimulus; contrast occurs when the judgment shifts in the opposite direction. Both effects are brought together and demonstrated in a single paradigm. It is hypothesized that the number of contextual stimuli is the differentiating factor. Two alternative hypotheses, the differential stimulation hypothesis and the temporal position hypothesis, are also tested. The differential stimulation hypothesis proposes that the intensity difference between the contextual and judged stimulus determines whether assimilation or contrast occur, and the temporal position hypothesis proposes that varying the temporal position of the contextual stimulus is the critical factor. While the results do not support either of these alternative hypotheses, it is shown that the number of contextual stimuli does determine whether assimilation or contrast occur.