Stimulation parameters influencing climbing fibre induced long-term depression of parallel fibre synapses

doi:10.1016/0168-0102(89)90065-5

Neuroscience Research

Volume 6, Issue 3, February 1989, Pages 264-268

https://doi.org/10.1016/0168-0102(89)90065-5 Get rights and content

Abstract

It has been demonstrated that conjunctive stimulation of cerebellar climbing fibres and parallel fibres induces a long-term depression (LTD) of the transmission from the activated parallel fibres to Purkinje cells. The aim of the present investigation with extracellular recordings from single Purkinje cells was to study factors influencing the induction of LTD. Climbing fibres and parallel fibres were conjunctively stimulated with a constant time interval between the climbing fibre and parallel fibre stimuli. It was demonstrated that the maximal effective time interval between climbing fibre and parallel fibre activation for induction of LTD was between 125 and 250 ms. It was also demonstrated that the amplitude of the LTD depended on the stimulation frequency. The LTD induced by conjunctive stimulation at 1 and 2 Hz had a similar size whereas the LTD induced by 4 Hz was stronger.

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Cited by (67)

Intrinsic memory of temporal intervals in cerebellar Purkinje cells
2019, Neurobiology of Learning and Memory
Citation Excerpt :
Similar rules for changes in synaptic strength can further be added to MLIs such that pf-MLI synapses that are active near the US undergo LTP and therefore more strongly suppress the Purkinje cell at the right time (Jörntell, Bengtsson, Schonewille, & De Zeeuw, 2010). LTD and LTP are readily inducible at both of these synapses both in vitro and in vivo with standard LTD/LTP induction protocols (Ekerot & Kano, 1989; Ito & Kano, 1982; Jörntell & Ekerot, 2002; Jörntell & Hansel, 2006; Linden, 1999; Sakurai, 1987). However, the literature is inconsistent regarding whether LTD is an essential mechanism in eyeblink conditioning where the induction protocols are significantly different (see below and Hesslow, Jirenhed, Rasmussen & Johansson, 2013).
The general consensus for learning and memory, including in the cerebellum, is that modification of synaptic strength via long-term potentiation (LTP) or long-term depression (LTD) are the primary mechanisms for the formation of memories. Recent findings suggest additional cellular mechanisms – referred to as ‘intrinsic plasticity’ – where a neuron's membrane excitability intrinsically changes. These mechanisms act like a dimmer and alter neuronal responsiveness by adjusting response amplitudes and spike thresholds. Here, I argue that classical conditioning of cerebellar Purkinje cell responses reveals yet another cell-intrinsic learning mechanism which significantly differs from both changes in synaptic strength and changes in membrane excitability.
When the conditional (CS) and unconditional stimuli (US) are delivered directly to the Purkinje cell's immediate pre-synaptic afferents, the parallel fibres and the climbing fibre, the cell learns to respond to the CS with a pause in its spontaneous firing that reflects the interval between the two stimuli. The pause response has a delayed onset and adaptively timed maximum, offset and duration, determined by the previously experienced CS-US interval. The timing is not dependent on any network-generated time-varying input. This implies the existence of a timing mechanism and a memory substrate that encodes the duration of the CS-US interval inside the Purkinje cell. Such temporal interval learning is not simply a change that causes more or less firing in response to an input. Here, I review these findings in relation to the standard theory of synaptic strength changes and the network interactions believed to be necessary for generating time codes.
Feedback delay attenuates implicit but facilitates explicit adjustments to a visuomotor rotation
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Citation Excerpt :
Nevertheless, previous studies on long-term depression (LTD) at synapses from parallel fibers to Purkinje cells in the cerebellum as a consequence of synchronized activity of climbing fibers and parallel fibers do suggest a potential cellular mechanism for a delay-dependent discounting of model-based adaptation. LTD at these synapses has been suggested as an important mechanism for the utilization of prediction errors that drive model-based adaptation (Miall, Weir, Wolpert, & Stein, 1993) and has further been demonstrated to peak at an inter stimulus interval (ISI) between climbing fiber and parallel fiber activation of 125 ms (Ekerot & Kano, 1989) and to decrease over a relatively long ISI range up to at least 1750 ms (Karachot, Kado, & Ito, 1994). It could thus potentially explain the decrease across the time range under consideration in our study.
We examined the effects of delaying terminal visual feedback on the relative contribution of explicit and implicit components of adaptation to a visuomotor rotation. Participants practiced a 30° rotation while receiving terminal visual feedback with either a short (0 ms), medium (200 ms), or long (1500 ms) delay. Explicit and implicit adjustments were dissociated by a series of posttests. While overall adaptation did not differ significantly between groups, aftereffects progressively decreased with increasing feedback delay. Moreover, explicit knowledge of the rotation increased in both the medium and high delay groups relative to the short delay group, but did not differ between the former two. This finding of feedback delay differentially affecting implicit adjustments as indexed by aftereffects and conscious strategic corrections based on explicit knowledge of the transformation substantiates the importance of distinguishing implicit and explicit components of adaptation even with rotations of smaller size and emphasizes the need to consider time delays in the interpretation of adaptation experiments and potentially in the design of training environments.
Classical conditioning of motor responses: What is the learning mechanism?
2013, Neural Networks
Citation Excerpt :
LTD, as traditionally conceived, cannot readily account for these results because it would be most effective at short delays between pf and cf input. Most work on LTD since it was first demonstrated has used simultaneous pf–cf input, so-called “conjunctive stimulation”, and comparisons of various delays between pf and cf stimulation have indicated that LTD is optimal when the delay is close to zero (Ekerot & Kano, 1989; Ito, 2001; Karachot, Kado, & Ito, 1995). In contrast, a couple of recent in vitro studies have reported that LTD does not, as originally claimed, work best with simultaneous climbing and parallel fibre input.
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.
Cerebellar Learning
2007, Neurobiology of Learning and Memory
This chapter focuses on the issue of cerebellar learning. It describes the evidence of cerebellar involvement in a number of forms of motor learning and adaptation and reviews evidence on the mechanisms underlying cerebellar learning, based on the unique advantages of eyelid conditioning, The evidence described in the chapter suggests that cerebellar learning is mediated by plasticity in the cerebellar cortex and in its downstream targets in the deep cerebellar nuclei. Bidirectional plasticity in the cerebellar cortex and deep cerebellar nucleus are controlled by climbing fibers and Purkinje Cells, respectively. The network dynamics of the cerebellar cortex creates a temporal code in the form of granule cells firing with different temporal delays during a CS, which can help shape the timing of cerebellar output vi2i gr-Pkj plasticity. The behavioral properties of eyelid conditioning to analyze the contribution of this learning in cerebellar information processing are also examined. The temporal properties of eyelid conditioning suggests that the cerebellar learning is involved in making temporally specific feed-forward predictions, a computation that is likely across the cerebellum, given its uniform circuitry. Also, the cerebellum learns temporally specific feed-forward predictions that are used to improve the operation of any neural process occurring on a relatively short time scale.
LTD - synaptic depression and memory storage
2007, Learning and Memory: A Comprehensive Reference
In neural networks, information can be stored by altering the efficacy of synaptic transmission. Synaptic plasticity therefore provides a candidate mechanism underlying learning and memory. Since its initial discovery in 1973, long-term potentiation (LTP) has been in the spotlight as a cellular correlate of various forms of learning, particularly those mediated by the hippocampus. Later, it was discovered that synapses can also undergo long-term depression (LTD), often in an activity-dependent way. In this article, we describe the molecular and cellular mechanisms of LTD induction and expression at (1) hippocampal Schaffer collateral-CA1 pyramidal cell synapses and (2) parallel fiber and climbing fiber synapses, respectively, onto cerebellar Purkinje cells. Using these types of synapses as examples, we characterize the different roles of LTD and compare bidirectional plasticity mechanisms at hippocampal and cerebellar synapses.
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^*: Present address: Department of Physiology, Jichi Medical School, Tochigi-ken, 329-04, Japan

^**: Present address: Department of Physiology and Biophysics. University of Lund, So¨lvegatan 19, S-223 62 Lund, Sweden.

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Stimulation parameters influencing climbing fibre induced long-term depression of parallel fibre synapses

Abstract

Brain Res.

Brain Res.

Brain Res.

Interaction between responses in Purkinje cells evoked by climbing fibre impulses and parallel fibre volleys

J. Physiol. (Lond.)

Prolonged depolarization elicited in Purkinje cell dendrites by climbing fibre impulses in the cat

J. Physiol. (Lond.)

Stimulation of cat cutaneous nociceptive C-fibres causing tonic and synchronous activity in climbing fibres

J. Physiol. (Lond.)