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3.
Hesslow, Germund, et al.
(författare)
Classical conditioning of motor responses: What is the learning mechanism?
2013
Ingår i: Neural Networks. - : Elsevier BV. - 1879-2782 .- 0893-6080. ; 47:Mar,28, s. 81-87
Tidskriftsartikel (refereegranskat) abstract
According to a widely held assumption, the main mechanism underlying motor learning in the cerebellum, such as eyeblink conditioning, is long-term depression (LTD) of parallel fibre to Purkinje cell synapses. Here we review some recent physiological evidence from Purkinje cell recordings during conditioning with implications for models of conditioning. We argue that these data pose four major challenges to the LTD hypothesis of conditioning. (i) LTD cannot account for the pause in Purkinje cell firing that is believed to drive the conditioned blink. (ii) The temporal conditions conducive to LTD do not match those for eyeblink conditioning. (iii) LTD cannot readily account for the adaptive timing of the conditioned response. (iv) The data suggest that parallel fibre to Purkinje cell synapses are not depressed after learning a Purkinje cell CR. Models based on metabotropic glutamate receptors are also discussed and found to be incompatible with the recording data.
4.
Johansson, Fredrik, et al.
(författare)
Memory trace and timing mechanism localized to cerebellar Purkinje cells
2014
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:41, s. 14930-14934
Tidskriftsartikel (refereegranskat) abstract
The standard view of the mechanisms underlying learning is that they involve strengthening or weakening synaptic connections. Learned response timing is thought to combine such plasticity with temporally patterned inputs to the neuron. We show here that a cerebellar Purkinje cell in a ferret can learn to respond to a specific input with a temporal pattern of activity consisting of temporally specific increases and decreases in firing over hundreds of milliseconds without a temporally patterned input. Training Purkinje cells with direct stimulation of immediate afferents, the parallel fibers, and pharmacological blocking of interneurons shows that the timing mechanism is intrinsic to the cell itself. Purkinje cells can learn to respond not only with increased or decreased firing but also with an adaptively timed activity pattern.
5.
Johansson, Fredrik, et al.
(författare)
Theoretical considerations for understanding a Purkinje cell timing mechanism
2014
Ingår i: Communicative & Integrative Biology. - : Informa UK Limited. - 1942-0889. ; 7:6, s. 994376-994376
Tidskriftsartikel (refereegranskat) abstract
In classical conditioning, cerebellar Purkinje cells learn an adaptively timed pause in spontaneous firing. This pause reaches its maximum near the end of the interstimulus interval. While it was thought that this timing was due to temporal patterns in the input signal and selective engagement of changes in synapse strength, we have shown Purkinje cells learn timed responses even when the conditional stimulus is delivered to its immediate afferents.(1) This shows that Purkinje cells have a cellular timing mechanism. The cellular models of intrinsic timing we are aware of are based on adapting the rise time of the concentration of a given ion. As an alternative, we here propose a selection mechanism in abstract terms for how a Purkinje cell could learn to respond at a particular time after an external trigger.
6.
Svensson, Pär, et al.
(författare)
Effect of conditioned stimulus parameters on timing of conditioned purkinje cell responses
2010
Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 103:3, s. 1329-1336
Tidskriftsartikel (refereegranskat) abstract
Pavlovian eyeblink conditioning is a useful experimental model for studying adaptive timing, an important aspect of skilled movements. The conditioned response (CR) is precisely timed to occur just before the onset of the expected unconditioned stimulus (US). The timing can be changed immediately, however, by varying parameters of the conditioned stimulus (CS). It has previously been shown that increasing the intensity of a peripheral CS or the frequency of a CS consisting of a train of stimuli to the mossy fibers shortens the latency of the CR. The adaptive timing of behavioral CRs probably reflects the timing of an underlying learned inhibitory response in cerebellar Purkinje cells. It is not known how the latency of this Purkinje cell CR is controlled. We have recorded form Purkinje cells in conditioned decerebrate ferrets while increasing the intensity of a peripheral CS or the frequency of a mossy fiber CS. We observe changes in the timing of the Purkinje cell CR that match the behavioral effects. The results are consistent with the effect of CS parameters on behavioral CR latency being caused by corresponding changes in Purkinje cell CRs. They suggest that synaptic temporal summation may be one of several mechanisms underlying adaptive timing of movements.
7.
Johansson, Fredrik, et al.
(författare)
Absence of Parallel Fibre to Purkinje Cell LTD During Eyeblink Conditioning
2018
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
Tidskriftsartikel (refereegranskat) abstract
Long-term depression (LTD) of parallel fibre/Purkinje cell synapses has been the favoured explanation for cerebellar motor learning such as classical eyeblink conditioning. Previous evidence against this interpretation has been contested. Here we wanted to test whether a classical conditioning protocol causes LTD. We applied a conditioning protocol, using a train of electrical pulses to the parallel fibres as the conditional stimulus. In order to rule out indirect effects caused by antidromic granule cell activation or output from Purkinje cells that might produce changes in Purkinje cell responsiveness, we focused the analysis on the first pulse in the conditional stimulus, that is, before any indirect effects would have time to occur. Purkinje cells learned to respond with a firing pause to the conditional stimulus. Yet, there was no depression of parallel fibre excitation after training.
8.
Andersson, G, et al.
(författare)
Evidence for a GABA-mediated cerebellar inhibition of the inferior olive in the cat
1988
Ingår i: Experimental Brain Research. - 0014-4819. ; 72:3, s. 450-456
Tidskriftsartikel (refereegranskat) abstract
1. Climbing fibres were activated by peripheral nerve stimulation at 'high' frequencies (greater than 3 Hz) for 15-25 s and then at 0.9 Hz for about 1 min. The high frequency activation induced a post-conditioning inhibition, lasting up to about 1 min, of climbing fibre responses recorded from the cerebellar surface. 2. Electrolytic lesions were made in the superior cerebellar peduncle (brachium conjunctivum). After the lesion, the post-conditioning inhibition was completely eliminated. 3. Injections of the GABA-receptor blocker bicuculline methiodide into the inferior olive reversibly blocked the post-conditioning inhibition. 4. The results support the hypothesis proposed by Andersson and Hesslow (1987a), that post-conditioning inhibition is mediated by a GABA-ergic interposito-olivary pathway.
9.
Bengtsson, Fredrik, et al.
(författare)
Cerebellar control of the inferior olive.
2006
Ingår i: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 5:1, s. 7-14
Forskningsöversikt (refereegranskat) abstract
A subpopulation of neurones in the cerebellar nuclei projects to the inferior olive, the source of the climbing fibre input to the cerebellum. This nucleo-olivary projection follows the zonal and, probably also, the microzonal arrangement of the cerebellum so that closed loops are formed between the neurones in the olive, the cerebellar cortex and the nuclei. The nucleo-olivary pathway is GABAergic, but several investigators argue that its main effect is to regulate electrotonic coupling between cells in the inferior olive rather than inhibit the olive. However, there is now strong evidence that the nucleo-olivary fibres do inhibit the olive. Three functions have been suggested for this inhibition: (i) feedback control of background activity in Purkinje cells, (ii) feedback control of learning, and (iii) gating of olivary input in general. Evidence is consistent with (i) and (ii). Activity in the nucleo-olivary pathway suppresses both synaptic transmission and background activity in the olive. When learned blink responses develop, the blink related part of the olive is inhibited while blinks are produced. When the nucleo-olivary pathway is interrupted, there is a corresponding increase in complex spike discharge in Purkinje cells followed by a strong suppression of simple spike firing. Stimulation of the pathway has the opposite results. It is concluded that the nucleo-olivary fibres are inhibitory and that they form a number of independent feedback loops, each one specific for a microcomplex, that regulate cerebellar learning as well as spontaneous activity in the olivo-cerebellar circuit.
10.
Bengtsson, Fredrik, et al.
(författare)
Extinction of conditioned blink responses by cerebello-olivary pathway stimulation
2007
Ingår i: NeuroReport. - 1473-558X. ; 18:14, s. 1479-1482
Tidskriftsartikel (refereegranskat) abstract
Learning of classically conditioned eyeblink responses depends on mechanisms within the cerebellum. It has been suggested that climbing fibres from the inferior olive transmit the unconditioned stimulus signal to the cerebellum. We have previously shown that the pathway from the deep cerebellar nuclei to the inferior olive inhibits olivary activity. It is known that repeated presentation of the conditioned stimulus on its own leads to extinction of the conditioned response. If the unconditioned stimulus signal is transmitted to the cerebellum via the inferior olive - climbing fibre system then stimulation of the nucleo-olivary pathway just before the unconditioned stimulus in a trained animal should lead to extinction. The results from this investigation confirm this.
