Multiple subclasses of Purkinje cells in the primate floccular complex provide similar signals to guide learning in the vestibulo-ocular reflex

The neural "learning rules" governing the induction of plasticity in the cerebellum were analyzed by recording the patterns of neural activity in awake, behaving animals during stimuli that induce a form of cerebellum-dependent learning. We recorded the simple- and complex-spike responses of a broad sample of Purkinje cells in the floccular complex during a number of stimulus conditions that induce motor learning in the vestibulo-ocular reflex (VOR). Each subclass of Purkinje cells carried essentially the same information about required changes in the gain of the VOR. The correlation of simple-spike activity in Purkinje cells with activity in vestibular pathways could guide learning during low-frequency but not high-frequency stimuli. Climbing fiber activity could guide learning during all stimuli tested but only if compared with the activity present approximately 100 msec earlier in either vestibular pathways or Purkinje cells.     

Neural circuitry and plasticity mechanisms underlying delay eyeblink conditioning

Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of parallel fiber synapses on Purkinje cells and long-term potentiation of mossy fiber synapses on neurons in the anterior interpositus nucleus. Conditioned stimulus and unconditioned stimulus inputs arise from the pontine nuclei and inferior olive, respectively, converging in the cerebellar cortex and deep nuclei. Projections from subcortical sensory nuclei to the pontine nuclei that are necessary for eyeblink conditioning are beginning to be identified, and recent studies indicate that there are dynamic interactions between sensory thalamic nuclei and the cerebellum during eyeblink conditioning. Cerebellar output is projected to the magnocellular red nucleus and then to the motor nuclei that generate the blink response(s). Tremendous progress has been made toward determining the neural mechanisms of delay eyeblink conditioning but there are still significant gaps in our understanding of the necessary neural circuitry and plasticity mechanisms underlying cerebellar learning.     

Cerebellar structure and function: making sense of parallel fibers

Many parts of the brain have to cooperate in a finely tuned way in order to generate coordinated motor output. Parameters of these cooperations are adjusted during early childhood development and years of motor learning later in life. The cerebellum plays a special role in the concert of these brain structures. With the unusual geometrical arrangement of its neuronal elements, especially of parallel fibers and Purkinje cells the cerebellum is a selective and sensitive detector of a specific class of spatio-temporal activity patterns in the mossy fiber system: sequences of excitatory input which 'move' along the direction of parallel fibers at about 0.5 m/s, i.e. the speed of spike conductance in parallel fibers. Precise spatio-temporal neuronal activity patterns have been shown to occur in two major sources of afference to the cerebellum, the neocortex and the sensory feedback system. Based on our own experimental work and the above-mentioned findings we suggest that the cerebellum detects specific spatio-temporal activity patterns which trigger learned cerebellar output related to motor control and which contributes to the control of precise timing of muscle contraction.     

Cerebellum and conditioned reflexes

The central assumption of existing models of motor learning in the cerebellum is that cerebellar mossy fibres signal information about the context in which a movement is to be performed and climbing fibres signal in relation to a movement error. This leads to changes in the responsiveness of Purkinje cells, which on the next occasion will generate a corrected output in a given context. Support for this view has come mainly from work on adaptation of the vestibulo-ocular reflex. The discovery that classically conditioned eyeblink responses depend critically on the cerebellum offers the possibility to study the learning of a novel behaviour, rather than modification of an existing reflex. After repeated pairing of a neutral stimulus, such as a tone, with a blink-eliciting stimulus, the tone will acquire the ability to elicit a blink on its own. We review evidence from studies employing a wide variety of techniques that the cerebellum is critical in this type of learning as well as evidence that mossy and climbing fibres have roles assigned to them in cerebellar learning models.     

Pontine stimulation overcomes developmental limitations in the neural mechanisms of eyeblink conditioning

Pontine neuronal activation during auditory stimuli increases ontogenetically between postnatal days (P) P17 and P24 in rats. Pontine neurons are an essential component of the conditioned stimulus (CS) pathway for eyeblink conditioning, providing mossy fiber input to the cerebellum. Here we examined whether the developmental limitation in pontine responsiveness to a CS in P17 rats could be overcome by direct stimulation of the CS pathway. Eyeblink conditioning was established in infant rats on P17-P18 and P24-P25 using pontine stimulation as a CS. There were no significant age-related differences in the rate or level of conditioning. Eyeblink conditioned responses established with the stimulation CS were abolished by inactivation of the ipsilateral cerebellar nuclei and overlying cortex in both age groups. The findings suggest that developmental changes in the CS pathway play an important role in the ontogeny of eyeblink conditioning.     

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.     

Electrophysiological evidence for a shared representational medium for visual images and visual percepts

Does mental imagery involve the activation of representations in the visual system? Systematic effects of imagery on visual signal detection performance have been used to argue that imagery and the perceptual processing of stimuli interact at some common locus of activity (Farah, 1985). However, such a result is neutral with respect to the question of whether the interaction occurs during modality-specific visual processing of the stimulus. If imagery affects stimulus processing at early, modality-specific stages of stimulus representation, this implies that the shared stimulus representations are visual, whereas if imagery affects stimulus processing only at later, amodal stages of stimulus representation, this implies that imagery involves more abstract, postvisual stimulus representations. To distinguish between these two possibilities, we repeated the earlier imagery-perception interaction experiment while recording event-related potentials (ERPs) to stimuli from 16 scalp electrodes. By observing the time course and scalp distribution of the effect of imagery on the ERP to stimuli, we can put constraints on the locus of the shared representations for imagery and perception. An effect of imagery was seen within 200 ms following stimulus presentation, at the latency of the first negative component of the visual ERP, localized at the occipital and posterior temporal regions of the scalp, that is, directly over visual cortex. This finding provides support for the claim that mental images interact with percepts in the visual system proper and hence that mental images are themselves visual representations.     

Interactions between prefrontal cortex and cerebellum revealed by trace eyelid conditioning

Eyelid conditioning has proven useful for analysis of learning and computation in the cerebellum. Two variants, delay and trace conditioning, differ only by the relative timing of the training stimuli. Despite the subtlety of this difference, trace eyelid conditioning is prevented by lesions of the cerebellum, hippocampus, or medial prefrontal cortex (mPFC), whereas delay eyelid conditioning is prevented by cerebellar lesions and is largely unaffected by forebrain lesions. Here we test whether these lesion results can be explained by two assertions: (1) Cerebellar learning requires temporal overlap between the mossy fiber inputs activated by the tone conditioned stimulus (CS) and the climbing fiber inputs activated by the reinforcing unconditioned stimulus (US), and therefore (2) trace conditioning requires activity that outlasts the presentation of the CS in a subset of mossy fibers separate from those activated directly by the CS. By use of electrical stimulation of mossy fibers as a CS, we show that cerebellar learning during trace eyelid conditioning requires an input that persists during the stimulus-free trace interval. By use of reversible inactivation experiments, we provide evidence that this input arises from the mPFC and arrives at the cerebellum via a previously unidentified site in the pontine nuclei. In light of previous PFC recordings in various species, we suggest that trace eyelid conditioning involves an interaction between the persistent activity of delay cells in mPFC-a putative mechanism of working memory-and motor learning in the cerebellum.Eyelid conditioning is a form of associative learning that has proven useful for mechanistic studies of learning (Thompson 1986). All variants of eyelid conditioning involve pairing a conditioned stimulus (CS, typically a tone) with a reinforcing unconditioned stimulus (US, mild electrical stimulation near the eye) to promote learned eyelid closure in response to the CS (also known as a conditioned response). Delay eyelid conditioning, where the CS and US overlap in time (Fig. 1A , left), is largely unaffected by forebrain lesions (Solomon et al. 1986; Mauk and Thompson 1987; Kronforst-Collins and Disterhoft 1998; Weible et al. 2000; Powell et al. 2001; McLaughlin et al. 2002) and engages the cerebellum relatively directly (but see Halverson and Freeman 2006). Presentation of the tone and the US are conveyed to the cerebellum via activation of mossy fibers and climbing fibers, respectively (Fig. 1B; Mauk et al. 1986; Steinmetz et al. 1987, 1989; Sears and Steinmetz 1991; Hesslow 1994; Hesslow et al. 1999). In addition, output via a cerebellar deep nucleus is required for the expression of conditioned responses (McCormick and Thompson 1984). This relatively direct mapping of stimuli onto inputs and of output onto behavior makes delay eyelid conditioning a powerful tool for the analysis of cerebellar learning and computation (Mauk and Donegan 1997; Medina and Mauk 2000; Medina et al. 2000, 2002; Hansel et al. 2001; Ohyama et al. 2003).Open in a separate windowFigure 1.The procedures, neural pathways, and putative signals involved in delay and trace eyelid conditioning. (A) Stimulus timing for delay (left) and trace (right) training trials. For delay conditioning, the US overlaps in time with the tone CS. In this and subsequent figures, green is used to indicate the presentation of the CS for delay conditioning. For trace conditioning, the US is presented after CS offset, and “trace interval” refers to the period between CS offset and US onset. For convenience, we used red and maroon regions to represent the CS and trace interval, respectively. Sample conditioned eyelid responses are shown below, for which an upward deflection indicates closure of the eyelid. (B) Schematic representation of the pathways engaged by delay conditioning. The CS and US, respectively, engage mossy fibers and climbing fibers relatively directly, and forebrain input is not required for normal learning. (C) The signals hypothesized to engage the cerebellum during trace conditioning. The activity of mossy fibers directly activated by the tone CS does not significantly outlast the stimulus. Thus, a forebrain structure is thought to provide an input that overlaps in time with the US and is necessary to produce cerebellar learning.Trace eyelid conditioning, where the US is presented after tone offset (Fig. 1A, right), has attracted interest for its potential to reveal the nature of interactions between the forebrain and cerebellum as well as the learning mechanisms within these systems. This potential stems from the sensitivity of trace conditioning not only to lesions of cerebellum but also to lesions of hippocampus, medial prefrontal cortex (mPFC), or mediodorsal thalamic nucleus (Woodruff-Pak et al. 1985; Moyer Jr. et al. 1990; Kronforst-Collins and Disterhoft 1998; Weible et al. 2000; Powell et al. 2001; McLaughlin et al. 2002; Powell and Churchwell 2002; Simon et al. 2005). Given the general inability of forebrain lesions to affect delay conditioning, these results have promoted the general interpretation that the forebrain and cerebellum interact to mediate trace conditioning (Weiss and Disterhoft 1996; Clark and Squire 1998; Clark et al. 2002).Here we test the specific hypotheses that (Fig. 1C) (1) cerebellar learning requires that mossy fiber and climbing fiber inputs overlap in time (or nearly so) and (2) that cerebellar learning in trace conditioning occurs in response to a forebrain-driven mossy fiber input that outlasts the CS to overlap with the US rather than the inputs activated by the tone CS (Clark et al. 2002). The data provide direct support for both assertions and, together with recent anatomical studies (Buchanan et al. 1994; Weible et al. 2007), reveal a pathway between the mPFC and cerebellum that is necessary for the expression of trace eyelid responses. When combined with previous recordings from PFC in primates and rodents (Funahashi et al. 1989; Bodner et al. 1996; Fuster et al. 2000; Narayanan and Laubach 2006), these data support the hypothesis that trace eyelid conditioning is mediated by interactions between working memory-related persistent activity in mPFC and motor learning mechanisms in the cerebellum.     

Cerebellar learning in the vestibulo-ocular reflex

The vestibulo-ocular reflex, because of its close relationship with the cerebellum and its marked adaptiveness, has become a model system for studying the functions of the cerebellum. It has been hypothesized that an evolutionarily old part of the cerebellum, the flocculus, forms a modifiable accessory pathway for the vestibulo-ocular reflex arc for adaptive control, and that the modification is due to the synaptic plasticity induced by retinal errors conveyed by a unique structure of the cerebellum, the climbing fibers. The flocculus hypothesis has been supported by several lines of evidence, including lesioning or functionally impairing the flocculus and recording the activity of flocculus Purkinje cells, and, more recently, from pharmacologically or genetically inhibited synaptic plasticity, which produces long-term depression. There has also been debate on a possible site for memory retention in vestibulo-ocular-reflex adaptation, and about the signal content in flocculus Purkinje cells. This article reviews recent studies on the learning mechanisms of the cerebellum that underlie the adaptation of the vestibulo-ocular reflex.     

Essential neuronal pathways for reflex and conditioned response initiation in an intracerebellar stimulation paradigm and the impact of unconditioned stimulus preexposure on learning rate

It has been demonstrated previously that pairing of tone CS and intracerebellar stimulation of lobule HVI white matter as the US produces conditioning that is robust and in many ways similar to that obtained with an airpuff US. The first study in this report addressed the effect of interpositus lesions on conditioned performance in rabbits trained with white matter stimulation as the US. It was found that interpositus lesions effectively eliminated the CR irrespective of the behavioral response measured. In addition, it was shown that the interpositus lesions also abolished the UR, providing strong evidence that the effects of the electrical stimulation were confined to the cerebellum and did not require the activation of brainstem structures. The second experiment examined performance on US-alone trials of varying durations. Response initiation within 100 ms of the US onset, regardless of US duration, indicated that reflex generation could not be due to rebound excitation of the interpositus following termination of Purkinje cell inhibition of that structure but instead likely reflects orthodromic activation of interpositus neurons via climbing fiber and/or mossy fiber collaterals. The impact of US preexposure on associative conditioning in this paradigm was also determined. Animals which received only 108 US-alone trials were massively impaired during subsequent training compared to rabbits that received fewer than 12 US-alone trials.     

Extinction as new learning versus unlearning: considerations from a computer simulation of the cerebellum

Like many forms of Pavlovian conditioning, eyelid conditioning displays robust extinction. We used a computer simulation of the cerebellum as a tool to consider the widely accepted view that extinction involves new, inhibitory learning rather than unlearning of acquisition. Previously, this simulation suggested basic mechanistic features of extinction and savings in eyelid conditioning, with predictions born out by experiments. We review previous work showing that the simulation reproduces behavioral phenomena and lesion effects generally taken as evidence that extinction does not reverse acquisition, even though its plasticity is bidirectional with no site dedicated to inhibitory learning per se. In contrast, we show that even though the sites of plasticity are, in general, affected in opposite directions by acquisition and extinction training, most synapses do not return to their naive state after acquisition followed by extinction. These results suggest caution in interpreting a range of observations as necessarily supporting extinction as unlearning or extinction as new inhibitory learning. We argue that the question “is extinction reversal of acquisition or new inhibitory learning?” is therefore not well posed because the answer may depend on factors such as the brain system in question or the level of analysis considered.Pavlovian eyelid conditioning is robustly bidirectional. Conditioned responses that are acquired via training that pairs a conditioned stimulus (CS) with an unconditioned stimulus (US) can be rapidly extinguished with CS-alone training or unpaired CS-US training (Gormezano et al. 1983; Napier et al. 1992; Macrae and Kehoe 1999; Kehoe and Macrae 2002; Kehoe and White 2002; Weidemann and Kehoe 2003). Whether extinction involves unlearning or separate inhibitory learning that suppresses conditioned response expression remains an important issue for both behavioral theories and for investigations of underlying neural mechanisms (Pavlov 1927; Hull 1943; Konorski 1948, 1967; Rescorla and Wagner 1972; Mackintosh 1974; Rescorla 1979; Bouton 1993, 2002; Falls 1998; Myers and Davis 2002; Kehoe and White 2002). Here, we addressed this issue using a computer simulation of the cerebellum that is capable of emulating many aspects of eyelid conditioning. Although simulation results cannot resolve such issues, several aspects of the simulation''s behavior are instructive. Even though the sites of plasticity are, in general, affected in opposite directions by acquisition and extinction training, the simulation can emulate several behavioral phenomena that are generally taken as evidence that extinction does not involve unlearning. Moreover, we found that the strengths of most synapses are quite different from their naive state following acquisition and then extinction. Independent of the overall biological accuracy of this simulation, these results highlight a variety of implications for ongoing debates about the roles of unlearning versus new learning in extinction.A combination of factors makes it possible to analyze the neural basis of eyelid conditioning in detail, and to build and test computer simulations of its cerebellar mechanisms (Medina and Mauk 2000). Foremost among these is the close association between eyelid conditioning and the cerebellum (Thompson 1986; Raymond et al. 1996; Mauk and Donegan 1997). Previous studies from several labs have shown that (1) cerebellar output drives the motor pathways that produce the conditioned responses (McCormick and Thompson 1984), (2) presentation of a CS is conveyed to the cerebellum via activation of certain of its mossy fiber inputs (Steinmetz et al. 1986; Hesslow et al. 1999), and (3) presentation of the US is conveyed via activation of certain climbing fiber inputs to the cerebellum (Fig. 1A; Mauk et al. 1986). These factors are complemented by the extent to which the synaptic organization and physiology of the cerebellum are known (Eccles et al. 1967; Ito 1984), as are the behavioral properties of eyelid conditioning (Gormezano et al. 1983; Kehoe and Macrae 2002). These advantages combine with the speed of current computers to make possible the construction of biologically detailed and large-scale computer simulations of the cerebellum that can then be thoroughly tested using standard eyelid conditioning protocols (Medina et al. 2000, 2001, 2002; Medina and Mauk 1999, 2000).Open in a separate windowFigure 1Emulation of eyelid conditioning in a computer simulation of the cerebellum. (A) A schematic representation of the simulation and how it was trained using an eyelid conditioning-like protocol. The output of the simulation comes from the summed activity of the six cerebellar deep nucleus cells (blue box). The CS was conveyed to the simulation by phasic activation of 18 of the 600 mossy fibers and tonic activation of six mossy fibers (green box). The US was emulated by a brief excitatory conductance applied to the single climbing fiber. The remainder of the simulation consisted of 10,000 granule cells, 900 Golgi cells, 20 stellate/basket cells, and 20 Purkinje cells with essentials of the connectivity as shown. (B) Acquisition, extinction, and savings by the simulation. Each panel shows the equivalent of 10 d of acquisition (left panel), extinction (center), and reacquisition (right) training. Individual sweeps are averages of 10 trials, which are clustered together to approximate the equivalent of one daily session of eyelid conditioning. These sessions are numbered at the left, progressing from front to back. The blue portion of the sweeps denotes the presence of the CS. (C) The strength of the mossy fiber-to-nucleus synapses in the simulation over the three phases of training. The synapses that progressively increase in strength during acquisition and reacquisition and decrease during extinction are the six that are tonically activated by the CS. Note that extinction training only slowly and thus incompletely reverses the strengthened synapses. Savings during reacquisition in the simulation is largely attributable to this residual plasticity. The continued increase in the strength of these synapses does not produce a comparable increase in response amplitude, rather, it reflects the tendency for the network to transfer plasticity from cortex (pauses in Purkinje activity produced by LTD) to the nucleus (increased strength of mossy fiber-to-nucleus synapses). How long this process continues depends on a number of unknown factors.The present results are more easily appreciated with a brief review of previous studies (Medina et al. 2000, 2001, 2002) showing how the simulation emulates acquisition, extinction, and savings during reacquisition. These phenomena are shown for the simulation in the three panels of Figure 1B. The underlying essential elements can be summarized briefly. Presentation of a CS activates subsets of granule cells, and these subsets change somewhat over the duration of the CS. Paired training induces long-term depression (LTD) at CS-activated granule-to-Purkinje synapses that are activated when the US is presented. This leads to a learned and well timed decrease in the activity of Purkinje cells during the CS (Hesslow and Ivarsson 1994), which leads to the induction of long-term potentiation (LTP) at mossy fiber-to-nucleus synapses activated by the CS. As this plasticity develops, nucleus cells encounter during the CS strong excitation combined with release from inhibition and therefore discharge robustly, thereby driving the expression of conditioned responses (McCormick and Thompson 1984). These steps suggest that learning first occurs in the cerebellar cortex, before robust conditioned responses are seen. We have observed evidence for this latent learning in cerebellar cortex (Ohyama and Mauk 2001).During extinction, CS-activated granule-to-Purkinje synapses undergo LTP because their activation occurs in the absence of climbing fiber activity. The essential suppression of climbing fiber activity below the typical level of 1 Hz is produced by inhibition from cerebellar output (Sears and Steinmetz 1991; Hesslow and Ivarsson 1996; Kenyon et al. 1998a,b; Miall et al. 1998), which is robust during the expression of conditioned responses. This prediction of the simulation is supported by observations that blocking inhibition of climbing fibers prevents extinction (Medina et al. 2002).We have shown previously that savings during reacquisition results, at least in part, from plasticity in the cerebellar deep nucleus that is relatively resistant to extinction (Medina et al. 2001). The strengths of the CS-activated mossy fiber-to-nucleus synapses in the simulation are shown in Figure 1C for acquisition, extinction, and reacquisition. Because learned pauses in Purkinje cell activity are still present early in extinction training, the strengths of CS-activated mossy fiber-to-nucleus synapses continue to increase. Once conditioned responses are fully extinguished, due to the restoration of robust Purkinje cell activity during the CS via the induction of LTP at CS-activated granule-to-Purkinje synapses, then CS-activated mossy fiber-to-nucleus synapses begin to undergo LTD and decrease in strength. The rate at which these synapses decrease in strength with additional extinction training depends on unknown factors such as the level of Purkinje activity required for induction of LTD. These results show in principle, however, that plasticity in the cerebellar cortex is sufficient to extinguish conditioned responses, and that a network displaying fully extinguished conditioned responses can still contain strengthened mossy fiber-to-nucleus synapses. In the simulation, savings occur largely because this residual plasticity in the cerebellar nucleus enhances the conditioned responses produced by the relearning of decreased activity in the Purkinje cells. In support, we have shown in rabbits that plasticity in the cerebellar nucleus persists following extinction, and that a measure of the magnitude of this residual plasticity correlates with the rate of reacquisition (Medina et al. 2001).Here, we used the mechanisms of extinction in this simulation to stimulate discussion regarding the issue of extinction as unlearning versus extinction as new learning.     

Asleep but aware?

Despite sleep-induced drastic decrease of self-awareness, human sleep allows some cognitive processing of external stimuli. Here we report the fortuitous observation in a patient who, while being recorded with intra-cerebral electrodes, was able, during paradoxical sleep, to reproduce a motor behaviour previously performed at wake to consciously indicate her perception of nociceptive stimulation. Noxious stimuli induced behavioural responses only if they reached the cortex during periods when mid-frontal networks (pre-SMA, pre-motor cortex) were pre-activated. Sensory responses in the opercular cortex and insula were identical whether the noxious stimulus was to evoke or not a motor behaviour; conversely, the responses in mid-anterior cingulate were specifically enhanced for stimuli yielding motor responses. Neuronal networks implicated in the voluntary preparation of movements may be reactivated during paradoxical sleep, but only if behavioural-relevant stimuli reach the cortex during specific periods of “motor awareness”. These local activation appeared without any global sleep stage change. This observation opens the way to further studies on the currently unknown capacity of the sleeping brain to interact meaningfully with its environment.     

Explicit authenticity and stimulus features interact to modulate BOLD response induced by emotional speech

Context has been found to have a profound effect on the recognition of social stimuli and correlated brain activation. The present study was designed to determine whether knowledge about emotional authenticity influences emotion recognition expressed through speech intonation. Participants classified emotionally expressive speech in an fMRI experimental design as sad, happy, angry, or fearful. For some trials, stimuli were cued as either authentic or play-acted in order to manipulate participant top-down belief about authenticity, and these labels were presented both congruently and incongruently to the emotional authenticity of the stimulus. Contrasting authentic versus play-acted stimuli during uncued trials indicated that play-acted stimuli spontaneously up-regulate activity in the auditory cortex and regions associated with emotional speech processing. In addition, a clear interaction effect of cue and stimulus authenticity showed up-regulation in the posterior superior temporal sulcus and the anterior cingulate cortex, indicating that cueing had an impact on the perception of authenticity. In particular, when a cue indicating an authentic stimulus was followed by a play-acted stimulus, additional activation occurred in the temporoparietal junction, probably pointing to increased load on perspective taking in such trials. While actual authenticity has a significant impact on brain activation, individual belief about stimulus authenticity can additionally modulate the brain response to differences in emotionally expressive speech.     

Purkinje cell activity in the cerebellar anterior lobe after rabbit eyeblink conditioning

The cerebellar anterior lobe may play a critical role in the execution and proper timing of learned responses. The current study was designed to monitor Purkinje cell activity in the rabbit cerebellar anterior lobe after eyeblink conditioning, and to assess whether Purkinje cells in recording locations may project to the interpositus nucleus. Rabbits were trained in an interstimulus interval discrimination procedure in which one tone signaled a 250-msec conditioned stimulus-unconditioned stimulus (CS-US) interval and a second tone signaled a 750-msec CS-US interval. All rabbits showed conditioned responses to each CS with mean onset and peak latencies that coincided with the CS-US interval. Many anterior lobe Purkinje cells showed significant learning-related activity after eyeblink conditioning to one or both of the CSs. More Purkinje cells responded with inhibition than with excitation to CS presentation. In addition, when the firing patterns of all conditioning-related Purkinje cells were pooled, it appeared that the population showed a pattern of excitation followed by inhibition during the CS-US interval. Using cholera toxin-conjugated horseradish peroxidase, Purkinje cells in recording areas were found to project to the interpositus nucleus. These data support previous studies that have suggested a role for the anterior cerebellar cortex in eyeblink conditioning as well as models of cerebellar-mediated CR timing that postulate that Purkinje cell activity inhibits conditioned response (CR) generation during the early portion of a trial by inhibiting the deep cerebellar nuclei and permits CR generation during the later portion of a trial through disinhibition of the cerebellar nuclei.     

The effect of brief auditory stimuli on visual apparent motion

When two discrete stimuli are presented in rapid succession, observers typically report a movement of the lead stimulus toward the lag stimulus. The object of this study was to investigate crossmodal effects of irrelevant sounds on this illusion of visual apparent motion. Observers were presented with two visual stimuli that were temporally separated by interstimulus onset intervals from 0 to 350 ms. After each trial, observers classified their impression of the stimuli using a categorisation system. The presentation of short sounds intervening between the visual stimuli facilitated the impression of apparent motion relative to baseline (visual stimuli without sounds), whereas sounds presented before the first and after the second visual stimulus as well as simultaneously presented sounds reduced the motion impression. The results demonstrate an effect of the temporal structure of irrelevant sounds on visual apparent motion that is discussed in light of a related multisensory phenomenon, 'temporal ventriloquism', on the assumption that sounds can attract lights in the temporal dimension.     

Repetition advantage and disadvantage in perceptual identification tasks

Repetitive presentation of a stimulus brings not only advantage but also disadvantage when performing perceptual identification tasks. In this study, the conflicting phenomena of the effect of repetition were examined using two Kana character sets (Hiragana and Katakana) as stimuli. Two identical or different stimuli were presented in rapid succession and participants were asked to identify and report them. The stimulus onset asynchrony (SOA) between the two stimuli was varied from 200 ms to 1200 ms, according to which the suitable temporal conditions for the two distinct effects of repetition were explored. The results indicated that two distinct effects of repetition occurred depending on the informational code shared by the two stimuli. An interference effect of repetition was observed with SOA values of up to 500 ms when the two stimuli were identical in terms of their visual pattern code (Hiragana), whereas a superior effect of repetition was observed with an SOA value of 200 ms when they were identical only in terms of their phonological code (Hiragana and Katakana). From these findings, the author proposes that when two identical stimuli are presented in rapid succession, inhibition and activation mechanisms may function at different levels of processing.     

Reversible inactivation of the hippocampal mossy fiber synapses in mice impairs spatial learning, but neither consolidation nor memory retrieval, in the Morris navigation task

The role played by hippocampal mossy fibers in the learning and memory processes implemented in the Morris swimming navigation task has been studied in C57BL/6 mice by selective and reversible inactivation of mossy fiber synaptic fields by diethyldithiocarbamate. The functional integrity of the mossy fibers proved essential for the storage of the spatial representation on the modifiable synapses of the recurrent collaterals of the CA3 pyramidal cells, whereas it is not necessary for the consolidation and recall of spatial memories. The results suggest that mossy fibers are preferentially involved in new learning. They are consistent with the hypothesis that the hippocampal CA3 region might act as an autoassociation memory.     

A model of cerebellar metaplasticity

The term "learning rule" in neural network theory usually refers to a rule for the plasticity of a given synapse, whereas metaplasticity involves a "metalearning algorithm" describing higher level control mechanisms for apportioning plasticity across a population of synapses. We propose here that the cerebellar cortex may use metaplasticity, and we demonstrate this by introducing the Cerebellar Adaptive Rate Learning (CARL) algorithm that concentrates learning on those Purkinje cell synapses whose adaptation is most relevant to learning an overall pattern. Our results show that this biologically plausible metalearning algorithm not only improves significantly the learning capability of the cerebellum but is very robust. Finally, we identify several putative neurochemicals that could be involved in a cascade of events leading to adaptive learning rates in Purkinje cell synapses.     

Validity and boundary conditions of automatic response activation in the Simon task.

Three experiments were conducted to determine whether spatial stimulus-response compatibility effects are caused by automatic response activation by stimulus properties or by interference between codes during translation of stimulus into response coordinates. The main evidence against activation has been that in a Simon task with hands crossed, responses are faster at the response location ipsilateral to the stimulus though manipulated by the hand contralateral to the stimulus. The experiments were conducted with hands in standard and in crossed positions and electroencephalogram measures showed coactivation of the motor cortex induced by stimulus position primarily during standard hand positions with visual stimuli. Only in this condition did the Simon effect decay with longer response times. The visual Simon effect appeared to be due to specific mechanisms of visuomotor information transmission that are not responsible for the effects obtained with crossed hands or auditory stimuli.