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CEREBELLAR LONG-TERM DEPRESSION AS INVESTIGATED IN A CELL CULTURE PREPARATION

Linden, David J. (1996) CEREBELLAR LONG-TERM DEPRESSION AS INVESTIGATED IN A CELL CULTURE PREPARATION.

Short Abstract:

Cerebellar long-term depression (LTD) is a form of synaptic plasticity, first described by Ito and co-workers, in which simultaneous activation of two excitatory inputs to a Purkinje neuron, the parallel fibers (PF) and the climbing fibers (CF), results in a sustained depression of PF synaptic drive. The purpose of this target article is not to assess the possible role of this synaptic alteration in motor learning, an issue which is addressed by other authors in this volume, nor is it to provide a detailed summary of the work on cerebellar LTD to this point (see Linden and Connor, 1993; Crepel et al., 1993 for review) or to place cerebellar LTD within the context of other forms of persistent synaptic depression that occur within the mammalian brain (see Linden, 1994b). Rather, it is to discuss results obtained using a very reduced preparation for the study of LTD, embryonic Purkinje neurons grown in culture and stimulated with exogenous excitatory amino acids, and to consider some advantages and limitations of this approach. Recent work using this preparation has suggested that three processes are necessary for the induction of cerebellar LTD, Ca influx through voltage-gated channels, Na influx through AMPA receptor-associated channels or voltage- gated Na channels, and protein kinase C activation which is dependent upon activation of the metabotropic glutamate receptor mGLUR1. In addition, input-specific induction of LTD has been demonstrated in this preparation under conditions where both spontaneous and evoked neurotransmitter release are reduced or eliminated, indicating that postsynaptic alterations are sufficient to confer this important computational property.

Long Abstract:

Cerebellar long-term depression (LTD) is a form of synaptic plasticity, first described by Ito and co-workers, in which simultaneous activation of two excitatory inputs to a Purkinje neuron, the parallel fibers (PF) and the climbing fibers (CF), results in a sustained depression of PF synaptic drive. The purpose of this target article is not to assess the possible role of this synaptic alteration in motor learning, an issue which is addressed by other authors in this volume, nor is it to provide a detailed summary of the work on cerebellar LTD to this point (see Linden and Connor, 1993; Crepel et al., 1993 for review) or to place cerebellar LTD within the context of other forms of persistent synaptic depression that occur within the mammalian brain (see Linden, 1994b). Rather, it is to discuss results obtained using a very reduced preparation for the study of LTD, embryonic Purkinje neurons grown in culture and stimulated with exogenous excitatory amino acids, and to consider some advantages and limitations of this approach. Recent work using this preparation has suggested that three processes are necessary for the induction of cerebellar LTD, Ca influx through voltage-gated channels, Na influx through AMPA receptor-associated channels or voltage- gated Na channels, and protein kinase C activation which is dependent upon activation of the metabotropic glutamate receptor mGLUR1. In addition, input-specific induction of LTD has been demonstrated in this preparation under conditions where both spontaneous and evoked neurotransmitter release are reduced or eliminated, indicating that postsynaptic alterations are sufficient to confer this important computational property.

Keywords:	Purkinje Neuron, Glutamate, Motor Learning, Synaptic Plasticity, Climbing Fiber, Parallel Fiber.
Subjects:	Psychology: Cognitive Psychology Neuroscience: Neuroanatomy Neuroscience: Neurochemistry Neuroscience: Neural Modelling Neuroscience: Neurology Neuroscience: Neurophysiology
ID code:	bbs00000525
Deposited by:	David Linden on 02 May 2001