Biomedical subjects

Michael D Mauk

Publications and source records attributed to Michael D Mauk.

9 recordsLinked to original sources

PubMed2006

Learning-induced plasticity in deep cerebellar nucleus.

Evidence that cerebellar learning involves more than one site of plasticity comes from, in part, pavlovian eyelid conditioning, where disconnecting the cerebellar cortex abolishes one component of learning, response timing, but spares the expression of abnormally timed short-latency responses (SLRs). Here, we provide evidence that SLRs unmasked by cerebellar cortex lesions are mediated by an associative form of learning-induced plasticity in the anterior interpositus nucleus (AIN) of the cerebellum. We used pharmacological inactivation and/or electrical microstimulation of various sites afferent and efferent to the AIN to systematically eliminate alternative candidate sites of plasticity upstream or downstream from this structure. Collectively, the results suggest that cerebellar learning is mediated in part by plasticity in target nuclei downstream of the cerebellar cortex. These data demonstrate an instance in which an aspect of associative learning, SLRs, can be used as an index of plasticity at a specific site in the brain.

Animals↗

PubMed2004

The neural basis of temporal processing.

A complete understanding of sensory and motor processing requires characterization of how the nervous system processes time in the range of tens to hundreds of milliseconds (ms). Temporal processing on this scale is required for simple sensory problems, such as interval, duration, and motion discrimination, as well as complex forms of sensory processing, such as speech recognition. Timing is also required for a wide range of motor tasks from eyelid conditioning to playing the piano. Here we review the behavioral, electrophysiological, and theoretical literature on the neural basis of temporal processing. These data suggest that temporal processing is likely to be distributed among different structures, rather than relying on a centralized timing area, as has been suggested in internal clock models. We also discuss whether temporal processing relies on specialized neural mechanisms, which perform temporal computations independent of spatial ones. We suggest that, given the intricate link between temporal and spatial information in most sensory and motor tasks, timing and spatial processing are intrinsic properties of neural function, and specialized timing mechanisms such as delay lines, oscillators, or a spectrum of different time constants are not required. Rather temporal processing may rely on state-dependent changes in network dynamics.

Animals↗

PubMed2003

What the cerebellum computes.

The brain is an organ that processes information. Brain systems such as the cerebellum receive inputs from other systems and generate outputs according to their internal rules of information processing. Thus, our understanding of the cerebellum is ultimately best expressed in terms of the information processing it accomplishes and how cerebellar neurons and synapses produce this processing. We review evidence that indicates how Pavlovian eyelid conditioning reveals cerebellar processing to be an example of feedforward control. Eyelid conditioning demonstrates a capacity for learning in the cerebellum that is error driven, associative and temporally specific--as is required for feedforward control. This computation-centered view is consistent with a variety of proposed functions of the cerebellum, including sensory-motor integration, motor coordination, motor learning and timing. Moreover, feedforward processing could be the common link between motor and non-motor functions of the cerebellum.

Animals↗

PubMed2003

Covariation of alternative measures of responding in rabbit (Oryctolagus cuniculus) eyeblink conditioning during acquisition training and tone generalization.

The likelihood, size, and speed of eyelid movements are thought to covary during the acquisition and expression of conditioning in rabbits (Oryctolagus cuniculus) and are generally accepted as interchangeable measures of the associative strength activated by the conditioned stimulus (CS). To test this assumption, the authors examined the patterns of covariation in these eyelid movement measures in acquisition and stimulus generalization in the upper eyelid and nictitating membrane. Rather than the expected covariation among these measures, eyelid movement magnitudes during the CS were distributed in approximately a bimodal manner. That is, eyelid activity consisted largely of a mixture of very small (< 0.125 mm) baseline measurements and larger (> 1 mm) movements. The results are discussed with respect to their implications for real-time models of eyelid conditioning.

Acoustic Stimulation↗

PubMed2002

Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses.

A fundamental tenet of cerebellar learning theories asserts that climbing fibre afferents from the inferior olive provide a teaching signal that promotes the gradual adaptation of movements. Data from several forms of motor learning provide support for this tenet. In pavlovian eyelid conditioning, for example, where a tone is repeatedly paired with a reinforcing unconditioned stimulus like periorbital stimulation, the unconditioned stimulus promotes acquisition of conditioned eyelid responses by activating climbing fibres. Climbing fibre activity elicited by an unconditioned stimulus is inhibited during the expression of conditioned responses-consistent with the inhibitory projection from the cerebellum to inferior olive. Here, we show that inhibition of climbing fibres serves as a teaching signal for extinction, where learning not to respond is signalled by presenting a tone without the unconditioned stimulus. We used reversible infusion of synaptic receptor antagonists to show that blocking inhibitory input to the climbing fibres prevents extinction of the conditioned response, whereas blocking excitatory input induces extinction. These results, combined with analysis of climbing fibre activity in a computer simulation of the cerebellar-olivary system, suggest that transient inhibition of climbing fibres below their background level is the signal that drives extinction.

Animals↗

PubMed2002

Parallels between cerebellum- and amygdala-dependent conditioning.

Recent evidence from cerebellum-dependent motor learning and amygdala-dependent fear conditioning indicates that, despite being mediated by different brain systems, these forms of learning might use a similar sequence of events to form new memories. In each case, learning seems to induce changes in two different groups of neurons. Changes in the first class of cells are induced very rapidly during the initial stages of learning, whereas changes in the second class of cells develop more slowly and are resistant to extinction. So, anatomically distinct cell populations might contribute differentially to the initial encoding and the long-term storage of memory in these two systems.

Amygdala↗

PubMed2002

Trying to understand the cerebellum well enough to build one.

The development of an increasingly detailed computer simulation of the cerebellum is briefly described. Specific and relatively direct evaluation of the performance of this simulation is made possible by the straightforward way in which pavlovian eyelid conditioning engages the cerebellum. Inputs to the simulation are based on recordings of mossy fiber and climbing fiber responses to the stimuli used in eyelid conditioning, and the output of the simulation can be evaluated with respect to the extensively characterized behavioral properties of eyelid conditioning. Because construction of the simulation has been guided by a strong aversion to errors of commission, both failures and successes of the simulation have proven informative. The behavior of the simulation related to the inhibitory nucleo-olivary feedback connection and spontaneous activity of climbing fibers is described. A prediction of the simulation concerning extinction is confirmed by experiment.

Animals↗

PubMedDate not supplied

Stimulus generalization of conditioned eyelid responses produced without cerebellar cortex: implications for plasticity in the cerebellar nuclei.

In Pavlovian eyelid conditioning and adaptation of the vestibulo-ocular reflex, cerebellar cortex lesions fail to completely abolish previously acquired learning, indicating an additional site of plasticity in the deep cerebellar or vestibular nucleus. Three forms of plasticity are known to occur in the deep cerebellar nuclei: formation of new synapses, plasticity at existing synapses, and changes in intrinsic excitability. Only a cell-wide increase in excitability predicts that learning should generalize broadly from a training stimulus to other stimuli capable of supporting learning, whereas the alternatives predict that learning should be relatively specific to the training stimulus. Here we show that deep nucleus plasticity, as assessed by conditioned eyelid responses produced without input from the cerebellar cortex, is relatively specific to the training conditioned stimulus (CS). We trained rabbits to a tone or light CS with periorbital stimulation as the unconditioned stimulus (US), and pharmacologically disconnected the cerebellar cortex during a posttraining generalization test. The short-latency conditioned responses unmasked by this treatment showed strong decrement along the dimension of auditory frequency and did not generalize across stimulus modalities. These results cannot be explained solely by a cell-wide increase in the excitability of deep nucleus neurons, and imply that an input-specific mechanism in the deep cerebellar nucleus operates as well.

Acoustic Stimulation↗

PubMedDate not supplied

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.

Association Learning↗