Elsevier

Cell Calcium

Volume 32, Issues 5–6, November–December 2002, Pages 405-411
Cell Calcium

Calcium stores and synaptic plasticity

https://doi.org/10.1016/S0143416002001999Get rights and content

Abstract

Chemical transmission at central synapses is known to be highly plastic; the strength of synaptic connections can be modified bi-directionally as a result of activity at individual synapses. Long-term changes in synaptic efficacy, both increases and decreases, are thought to be involved in the development of the nervous system, and in ongoing changes in response to external cues such as during learning and addiction. Other, shorter lasting changes in synaptic transmission are also likely to be important in normal functioning of the CNS. Calcium mobilisation is an important step in multiple forms of plasticity and, although entry into neurones from the extracellular space is often the initial trigger for plasticity changes, release of calcium from intracellular stores also has an important part to play in a variety of forms of synaptic plasticity.

Section snippets

INTRODUCTION

The ability to modify synaptic connections is a fundamental property of the CNS. During development, synapses are strengthened and weakened and during life changes occur as a result of incoming information. Thus processes such as learning, memory and addiction involve changes in synaptic transmission. At the cellular level, long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission have received much attention as models of learning and memory (for example, see [1]).

HIPPOCAMPAL NMDA RECEPTOR-DEPENDENT PLASTICITY

At the CA3-CA1 synapses in the hippocampus, AMPA receptors mediate the vast majority of basal transmission whereas NMDA receptors are largely silent during basal periods due to a block by Mg2+ ions at negative membrane potentials [8]. NMDA receptor activation, however, is a critical trigger for the induction of both LTP and LTD in the hippocampus and other brain regions 2., 3.. For example, at the CA3-CA1 synapse in the hippocampus, blockade of NMDA receptors prevents the induction of LTP [9]

CEREBELLAR LTD

The role of calcium release from the ER is clearer in the case of LTD in the cerebellum than in LTP and LTD in the hippocampus. Purkinje cells (PCs) in the cerebellar cortex receive inputs from the inferior olive via climbing fibres (CFs) and from granule cells in the cerebellum via parallel fibres (PFs; reviewed in [30]). Repeated associative activation of the two inputs onto a single Purkinje cell results in LTD of the PF input. Cerebellar LTD is thought to be critical for various types of

SHORT-TERM PLASTICITY AT PRESYNAPTIC TERMINALS

The plasticity described above, both in the hippocampus and cerebellum, involves calcium release from the ER in the postsynaptic neurone. However, ER and the associated ryanodine receptors are also present in presynaptic axon terminals [43]. Basal action potential-stimulated release of transmitter is known to be elicited by calcium entry through voltage gated calcium channels, but the role of CICR in the presynaptic terminal is unclear. Emptage et al. [44] recently investigated whether calcium

OTHER FORMS OF SYNAPTIC PLASTICITY

In addition to the main forms of plasticity discussed above, release of calcium from intracellular stores may also be involved in other forms of plasticity in the CNS. High frequency stimulation of afferent fibres to CA3 pyramidal cells elicits an LTD of inhibitory GABAA receptor-mediated responses [47]. Such LTD is prevented by inhibitors of CICR, but not by inhibitors of IP3-mediated calcium release, and the calcium stores involved may be located both pre and postsynaptically [47]. LTP of GABA

CONCLUSION

Rises in intracellular calcium levels is a common property of multiple forms of synaptic plasticity. In some cases calcium entry through NMDA receptors is the initial trigger for plasticity changes which may then also include CICR from ER. Activation of mglu receptors can also contribute to plasticity induction by stimulating calcium release from the ER via production of IP3. Several forms of plasticity are known to be inhibited by blocking calcium release from intracellular stores but until

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