An Associative Memory Trace in the Cerebellar Cortex

Classical conditioning of motor responses, e.g., the eyeblink response, depends on the cerebellum. In the theoretical works of David Marr (1969) and James Albus (1971), it was proposed that Purkinje cells in the cerebellar cortex learn to associate the neutral conditioned stimulus with the response. Since their work, several studies have provided data that are consistent with this suggestion, but definitive evidence has been lacking. Information on how Purkinje cells change their activity during learning has been ambiguous and contradictory and there has been no information at all about how they behave during extinction and reacquisition. The electrical activity of single Purkinje cells was recorded with microelectrodes in decerebrate ferrets during learning, extinction, and relearning. We demonstrate that paired peripheral forelimb and periocular stimulation, as well as paired direct stimulation of cerebellar afferent pathways (mossy and climbing fibres) consistently causes a gradual acquisition of an inhibitory response in Purkinje cell simple spike firing. The response also displays gradual extinction to unpaired presentations of the stimuli, and reacquisition with substantial savings when paired stimulus presentation is reinstated. This conditioned Purkinje cell response thus has several properties that match known features of the conditioned eyeblink response across training trials. The temporal properties of the conditioned Purkinje cell response were also investigated. The response maximum was adaptively timed to precede the unconditioned stimulus. The latencies to response onset, maximum, and offset varied with the interstimulus interval used during training. Further training with changes in the interstimulus interval caused new learning of response latencies. Finally, short-term manipulations of the conditioned stimulus after training had effects on the Purkinje cell response that match effects on the conditioned eyeblink response. These data suggest that many of the behavioural phenomena in eyeblink conditioning can be explained at the level of the single Purkinje cell

Time Course of Classically Conditioned Purkinje Cell Response is Determined by Initial Part of Conditioned Stimulus

Classical conditioning of a motor response such as eyeblink is associated with the development of a pause in cerebellar Purkinje cell firing that is probably an important driver of the overt response. This conditioned Purkinje cell response is adaptively timed and has a specific temporal profile that probably explains the time course of the overt behavior. It is generally assumed that the temporal properties of the conditioned Purkinje cell response are determined by the temporal pattern of the parallel fiber impulses generated by the conditioned stimulus at the time of the conditioned response. We show here in the decerebrate ferret preparation that a very brief conditioned stimulus, consisting of only one or two impulses in the mossy fibers, can be sufficient to elicit a full conditioned Purkinje cell response with normal time course. The finding suggests that parallel fiber input to the Purkinje cell influences the firing rate several hundred milliseconds later. It poses a serious challenge to the standard view of the role of parallel fiber impulses in response timing

Parallel fiber and climbing fiber responses in rat cerebellar cortical neurons in vivo.

Over the last few years we have seen a rapidly increasing interest in the functions of the inhibitory interneurons of the cerebellar cortex. However, we still have very limited knowledge about their physiological properties in vivo. The present study provides the first description of their spontaneous firing properties and their responses to synaptic inputs under non-anesthetized conditions in the decerebrated rat in vivo. We describe the spike responses of molecular layer interneurons (MLI) in the hemispheric crus1/crus2 region and compare them with those of Purkinje cells (PCs) and Golgi cells (GCs), both with respect to spontaneous activity and responses evoked by direct electrical stimulation of parallel fibers (PFs) and climbing fibers (CFs). In agreement with previous findings in the cat, we found that the CF responses in the interneurons consisted of relatively long lasting excitatory modulations of the spike firing. In contrast, activation of PFs induced rapid but short-lasting excitatory spike responses in all types of neurons. We also explored PF input plasticity in the short-term (10 min) using combinations of PF and CF stimulation. With regard to in vivo recordings from cerebellar cortical neurons in the rat, the data presented here provide the first demonstration that PF input to PC can be potentiated using PF burst stimulation and they suggest that PF burst stimulation combined with CF input may lead to potentiation of PF inputs in MLIs. We conclude that the basic responsive properties of the cerebellar cortical neurons in the rat in vivo are similar to those observed in the cat and also that it is likely that similar mechanisms of PF input plasticity apply

Learning and Timing of voluntary blink responses match eyeblink conditioning

Can humans produce well-timed blink responses to a neutral stimulus voluntarily, without receiving any blink-eliciting, unconditional, stimulus? And if they can, to what degree does classical eyeblink conditioning depend on volition? Here we show that voluntary blink responses learned in two paradigms that did not involve any unconditional blink-eliciting stimuli, display timing that is as good, or better than, the timing of blink responses learned in a standard eyeblink conditioning paradigm. The exceptional timing accuracy likely stems from the fact that, in contrast to previous studies, we challenged our participants to blink in a timed manner, and not merely to blink so as to avoid the corneal air puff. These results reveal a remarkable level of voluntary control over a simple movement, and they challenge the view that learning during eyeblink conditioning is necessarily automatic and involuntary

The inner world of a simple robot

The purpose of the paper is to discuss whether a particular robot can be said to have an 'inner world', something that can be taken to be a critical feature of consciousness. It has previously been argued that the mechanism underlying the appearance of an inner world in humans is an ability of our brains to simulate behaviour and perception. A robot has previously been designed in which perception can be simulated. A prima facie case can be made that this robot has an inner world in the same sense as humans. Various objections to this claim are discussed in the paper and it is concluded that the robot, although extremely simple, can easily be improved without adding any new principles, so that ascribing an inner world to it becomes intuitively reasonable

Learning Stimulus Intervals – Adaptive Timing of Conditioned Purkinje Cell Responses

Classical conditioning of motor responses, such as the eyeblink response, is an experimental model of associative learning and of adaptive timing of movements. A conditioned blink will have its maximum amplitude near the expected onset of the unconditioned blink-eliciting stimulus and it adapts to changes in the interval between the conditioned and unconditioned stimuli. Previous studies have shown that an eyeblink conditioning protocol can make cerebellar Purkinje cells learn to pause in response to the conditioned stimulus. According to the cerebellar cortical conditioning model, this conditioned Purkinje cell response drives the overt blink. If so, the model predicts that the temporal properties of the Purkinje cell response reflect the overt behaviour. To test this prediction, in vivo recordings of Purkinje cell activity were performed in decerebrate ferrets during conditioning, using direct stimulation of cerebellar mossy and climbing fibre afferents as conditioned and unconditioned stimuli. The results show that Purkinje cells not only develop a change in responsiveness to the conditioned stimulus. They also learn a particular temporal response profile where the timing, not only of onset and maximum but also of offset, is determined by the temporal interval between the conditioned and unconditioned stimuli

Are Purkinje Cell Pauses Drivers of Classically Conditioned Blink Responses?

Several lines of evidence show that classical or Pavlovian conditioning of blink responses depends on the cerebellum. Recordings from cerebellar Purkinje cells that control the eyelid and the conditioned blink show that during training with a conditioning protocol, a Purkinje cell develops a pause response to the conditional stimulus. This conditioned cellular response has many of the properties that characterise the overt blink. The present paper argues that the learned Purkinje cell pause response is the memory trace and main driver of the overt conditioned blink and that it explains many well-known behavioural phenomena

Effects of working memory load and CS-US intervals on delay eyeblink conditioning

Abstract Eyeblink conditioning is used in many species to study motor learning and make inferences about cerebellar function. However, the discrepancies in performance between humans and other species combined with evidence that volition and awareness can modulate learning suggest that eyeblink conditioning is not merely a passive form of learning that relies on only the cerebellum. Here we explored two ways to reduce the influence of volition and awareness on eyeblink conditioning: (1) using a short interstimulus interval, and (2) having participants do working memory tasks during the conditioning. Our results show that participants trained with short interstimulus intervals (150 ms and 250 ms) produce very few conditioned responses after 100 trials. Participants trained with a longer interstimulus interval (500 ms) who simultaneously did working memory tasks produced fewer conditioned responses than participants who watched a movie during the training. Our results suggest that having participants perform working memory tasks during eyeblink conditioning can be a viable strategy for studying cerebellar learning that is absent of influences from awareness and volition. This could enhance the comparability of the results obtained in human studies with those in animal models

Simple and Complex Spike Firing Patterns in Purkinje Cells During Classical Conditioning.

Classical blink conditioning is known to depend critically on the cerebellum and the relevant circuitry is gradually being unravelled. Several lines of evidence support the theory that the conditioned stimulus is transmitted by mossy fibers to the cerebellar cortex whereas the unconditioned stimulus is transmitted by climbing fibers. This view has been dramatically confirmed by recent Purkinje cell recordings during training with a classical conditioning paradigm. We have tracked the activity of single Purkinje cells with microelectrodes for several hours in decerebrate ferrets during learning, extinction, and relearning. Paired peripheral forelimb and periocular stimulation, as well as paired direct stimulation of cerebellar afferent pathways (mossy and climbing fibers) causes acquisition of a pause response in Purkinje cell simple spike firing. This conditioned Purkinje cell response has temporal properties that match those of the behavioral response. Its latency varies with the interstimulus interval and it responds to manipulations of the conditioned stimulus in the same way that the blink does. Complex spike firing largely mirrors the simple spike behavior. We have previously suggested that cerebellar learning is subject to a negative feedback control via the inhibitory nucleo-olivary pathway. As the Purkinje cell learns to respond to the conditioned stimulus with a suppression of simple spikes, disinhibition of anterior interpositus neurons would be expected to cause inhibition of the inferior olive. Observations of complex spike firing in the Purkinje cells during conditioning and extinction confirm this prediction. Before training, complex spikes are unaffected or facilitated by the conditioned stimulus, but as the simple spike pause response develops, spontaneous and stimulus-evoked complex spikes are also strongly suppressed by the conditioned stimulus. After extinction of the simple spike pause response, the complex spikes reappear