The role of calcium in synaptic plasticity and motor learning in the cerebellar cortex

doi:10.1016/j.neubiorev.2012.01.005

Neuroscience & Biobehavioral Reviews

Volume 36, Issue 4, April 2012, Pages 1153-1162

https://doi.org/10.1016/j.neubiorev.2012.01.005 Get rights and content

Abstract

The cerebellum is important for motor coordination, as well as motor learning and memories. Learning is believed to occur in the cerebellar cortex, in the form of synaptic plasticity. Central to motor learning theory are Purkinje cells (PCs), which are the sole output neurons of the cerebellar cortex. Motor memories are postulated to be stored in the form of long-term depression (LTD) at parallel fiber synapses with PCs, once thought to be the only plastic synapse in the cerebellar cortex. However, in the past few decades many studies have demonstrated that several other synapses in the cerebellar cortex are indeed plastic, and that LTD or long-term potentiation at these various synapses could affect the overall output signal of PCs from the cerebellar cortex. Almost all of these forms of synaptic plasticity are dependent on calcium to some extent. In the current review we discuss various types of synaptic plasticity in the cerebellar cortex and the role of calcium in these forms of plasticity.

Highlights

► Calcium contributes to most forms of synaptic plasticity in the cerebellar cortex. ► Calcium-dependent plasticity may influence motor coordination and learning. ► Many mutant mouse models with altered calcium signaling exhibit motor dysfunction.

Introduction

The cerebellum, which is Latin for “little brain”, lies posterior to the pons and medulla oblongata and inferior to the occipital lobes of the cerebral hemispheres. Cerebellar damage often leads to symptoms such as ataxia, asynergy, dysmetria, and motor learning deficits in humans (Schmahmann, 2004, Stoodley and Schmahmann, 2010) as well as in animals (Lalonde and Strazielle, 2001, Rinaldo and Hansel, 2010). Therefore, the ability to modulate motor commands and fine-tune complex movements has largely been attributed to the cerebellum. Recent evidence suggests that the cerebellum may have cognitive functions and play a role in the processing of emotions (Strick et al., 2009). In addition, the cerebellum has received considerable attention because of its proposed role in motor learning behavior (Ito, 2006). Central to motor learning theories are Purkinje cells (PCs) of the cerebellar cortex. PCs are important because they represent the only output cell of the cerebellar cortex and as such, play a vital role in normal cerebellar function, i.e. motor coordination. In addition to motor coordination, PCs are postulated to play a major role in certain forms of motor learning, including associative eyeblink conditioning and adaptation of the vestibulo-ocular reflex (Schmolesky et al., 2002). Synaptic plasticity in PCs has long been postulated to represent the underlying cellular changes that lead to motor memories. Long term depression (LTD) at parallel fiber (PF)-PC synapses in particular remains a widely accepted vertebrate model for the cellular mechanism that underlies synaptic changes during motor learning and memories in the cerebellum, and several molecular components have been identified which appear to be necessary for its induction, including glutamate receptors and various kinases (Massey and Bashir, 2007). It was long thought that PF-PC synapses were the only synapses capable of plasticity in the cerebellar cortex, however in recent years plasticity has been described at several other synapses in the cortex (Hansel et al., 2001, Dean et al., 2010). In this review, we provide a brief overview of the types of synaptic plasticity present in the cerebellar cortex, with a particular emphasis on the role of calcium in those synaptic changes.

Section snippets

Basic circuit in the cerebellar cortex

The cell bodies of PCs are found in a specific layer of the cerebellar cortex appropriately named, the PC layer. The dendrites of PCs project into the molecular layer of the cortex, while the axons of PCs pass through the granule cell (GC) layer and project out of the cerebellar cortex (see Fig. 1). PCs receive two types of excitatory synaptic inputs. The first is from climbing fibers (CFs), which arise from the inferior olive (IO) of the brain stem and carry sensory, and perhaps motor

The role of calcium in cell signaling

The calcium ion (Ca²⁺) is arguably one of the most important, if not the most important ion in the nervous system, because of the wide variety of activities in which it is reported to be involved. For example, Ca²⁺ is intricately involved in the growth and development of neurons (Ghosh and Greenberg, 1995, Spitzer and Ribera, 1998, Takei et al., 1998) and it is a necessary component for normal neurotransmission in the brain (Berridge, 1998, Iwasaki et al., 2000), spinal cord (Bertrand et al.,

Purkinje cells

Activation of groups of PFs in vitro causes the release of glutamate into the synaptic cleft, which results in brief excitatory postsynaptic potentials (EPSPs; Eilers et al., 1995). If the stimulation intensity is high enough, the result is the generation of action potentials in PCs termed simple spikes, which can occur at various frequencies in vivo depending on various vestibular and motor signals (Barmack and Yakhnitsa, 2003, Dean et al., 2010). Activation, and release of glutamate from CFs,

Insights from transgenic mouse models

Immense strides have been made to advance techniques used to research calcium's involvement with cerebellar plasticity and motor learning. One of the most useful techniques is the utilization of genetic knockout mice or other mutant mice, as it allows for this phenomenon to be studied in more detail in vivo. Many varieties of mutant mice are available for studies of cerebellar plasticity and signaling, such as the hotfoot mouse (Draski et al., 1994, Mandolesi et al., 2009). The hotfoot mouse

Summary and concluding remarks

The cerebellum has long been accepted as a part of the brain involved with fine motor coordination and learning. As described, there are many components to the circuit in the cerebellar cortex. Original motor learning theories suggested that learning took place solely at the synapses between PFs and PCs, and that most, if not all other synapses in the cerebellar cortex were not plastic. Clearly, this view was overly simplistic, as plasticity has now been described at several synapses in the

Acknowledgments

The authors would like to acknowledge current research funding support from the Natural Sciences and Engineering Research Council (NSERC) and the Canada Foundation for Innovation.

References (138)

A. Alba et al.
Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice
Cell
(1994)
J.S. Albus
A theory of cerebellar function
Math. Biosci.
(1971)
B. Barbour et al.
What can we learn from synaptic weight distributions?
Trends Neurosci.
(2007)
M.J. Berridge
Neuronal calcium signalling
Neuron
(1998)
S. Bertrand et al.
N- and P/Q-type Ca²⁺ channels are involved in neurotransmitter release but not in synaptic depression in the spinal cord of the neonatal rat
Neurosci. Lett.
(2000)
A. Bouron
Activation of a capacitative Ca²⁺ entry pathway by store depletion in cultured hippocampal neurones
FEBS Lett.
(2000)
V. Bruno et al.
Activation of metabotropic glutamate receptors coupled to inositol phospholipid hydrolysis amplifies NMDA-induced neuronal degeneration in cultured cortical cells
Neuropharmacology
(1995)
L.J. Draski et al.
CNS monoamine levels and motoric behaviors in the hotfoot ataxic mutant
Brain Res.
(1994)
G.P. Dugué et al.
Electrical coupling mediates tunable low-frequency oscillations and resonance in the cerebellar Golgi cell network
Neuron
(2009)
J.A. Dzubay et al.
Climbing fibre activation of metabotropic glutamate receptors on cerebellar Purkinje neurons
Neuron
(2002)

L.J. Gentet et al.

Membrane potential dynamics of GABAergic neurons in the barrel cortex of behaving mice

Neuron

(2010)

C. Hansel et al.

Long-term depression of the cerebellar climbing fibre—Purkinje neuron synapse

Neuron

(2000)

C. Hansel et al.

Alpha-CaMKII is essential for cerebellar LTD and motor learning

Neuron

(2006)

N.A. Hartell

Strong activation of parallel fibres produces localized calcium transients and a form of LTD that spreads to distant synapses

Neuron

(1996)

F.E. Hoebeek et al.

Increased noise level of Purkinje cell activities minimizes impact of their modulation during sensorimotor control

Neuron

(2005)

M. Ito et al.

Long-lasting depression of parallel fibre-Purkinje cell transmission induced by conjunctive stimulation of parallel fibres and climbing fibres in the cerebellar cortex

Neurosci. Lett.

(1982)

M. Ito

Cerebellar circuitry as a neuronal machine

Prog. Neurobiol.

(2006)

Y. Jin et al.

Long-term depression of mGluR1 signaling

Neuron

(2007)

H. Jörntell et al.

Reciprocal bidirectional plasticity of parallel fiber receptive fields in cerebellar Purkinje cells and their afferent interneurons

Neuron

(2002)

H. Jörntell et al.

Synaptic memories upside down: bidirectional plasticity at cerebellar parallel fibre-Purkinje cell synapses

Neuron

(2006)

R. Lalonde et al.

Motor performance and regional brain metabolism of spontaneous murine mutations with cerebellar atrophy

Behav. Brain Res.

(2001)

L.S. Lerea et al.

Ionotropic glutamate receptor subtypes activate c-fos transcription by distinct calcium-requiring intracellular signaling pathways

Neuron

(1993)

J. Lisman et al.

A model of synaptic memory: a CaMKII/PP1 switch that potentiates transmission by organizing an AMPA receptor anchoring assembly

Neuron

(2001)

I. Llano et al.

Intradendritic release of calcium induced by glutamate in cerebellar Purkinje cells

Neuron

(1991)

P.V. Massey et al.

Long-term depression: multiple forms and implications for brain function

Trends Neurosci.

(2007)

T. Nagase et al.

Long-term potentiation and long-term depression in hippocampal CA1 neurons of mice lacking the IP₃ type 1 receptor

Neuroscience

(2003)

A.B. Nelson et al.

Decreases in CaMKII activity trigger persistent potentiation of intrinsic excitability in spontaneously firing vestibular nucleus neurons

Neuron

(2005)

Y. Okubo et al.

Visualization of IP₃ dynamics reveals a novel AMPA receptor-triggered IP3 production pathway mediated by voltage-dependent Ca²⁺ influx in Purkinje cells

Neuron

(2001)

S. Ozawa et al.

Glutamate receptors in the mammalian central nervous system

Prog. Neurobiol.

(1998)

M. Palkovits et al.

Quantitative histological analysis of the cerebellar cortex in the cat. II. Cell numbers and densities in the granular layer

Brain Res.

(1971)

A. Pellionisz et al.

Dynamic single unit simulation of a realistic cerebellar network model

Brain Res.

(1973)

A.L. Person et al.

Deactivation of L-type Ca current by inhibition controls LTP at excitatory synapses in the cerebellar nuclei

Neuron

(2010)

A. Pisani et al.

Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-d-aspartate responses in medium spiny striatal neurons

Neuroscience

(2001)

B. Pöschel et al.

Group II m-GluR-induced long term depression in the dentate gyrus in vivo in NMDA receptor-independent and does not require protein synthesis

Neuropharmacology

(2005)

H. Alle et al.

GABAergic spill-over transmission onto hippocampal mossy fibre boutons

J. Neurosci.

(2007)

G. Ariav et al.

Submillisecond precision of the input–output transformation function mediated by fast sodium dendritic spikes in basal dendrites of CA1 pyramidal neurons

J. Neurosci.

(2003)

A. Baba et al.

Activity-evoked capacitative Ca²⁺ entry: implications in synaptic plasticity

J. Neurosci.

(2003)

H. Bading et al.

Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways

Science

(1993)

N.H. Barmack et al.

Cerebellar climbing fibres modulate simple spikes in Purkinje cells

J. Neurosci.

(2003)

A. Belmeguenai et al.

A role for protein phosphatases 1, 2A, and 2B in cerebellar long-term potentiation

J. Neurosci.

(2005)

T.V. Bliss et al.

A synaptic model of memory: long-term potentiation in the hippocampus

Nature

(1993)

R.M. Bruno

Cortex is driven by weak but synchronously active thalamocortical synapses

Science

(2006)

A.G. Carter et al.

Quantal events shape cerebellar interneuron firing

Nat. Neurosci.

(2002)

P. Chadderton et al.

Integration of quanta in cerebellar granule cells during sensory processing

Nature

(2004)

M. Coesmans et al.

Bidirectional parallel fibre plasticity in the cerebellum under climbing fibre control

Neuron

(2004)

V. Coutinho et al.

Metabotropic glutamate receptors: electrical and chemical signaling properties

Neuroscientist

(2002)

S. Crochet et al.

Selective amplification of neocortical neuronal output by fast prepotentials in vivo

Cereb. Cortex

(2004)

E. D’Angelo

The critical role of Golgi cells in regulating spatio-temporal integration and plasticity at the cerebellum input stage

Front. Neurosci.

(2008)

J.T. Davie et al.

The origin of the complex spike in cerebellar Purkinje cells

J. Neurosci.

(2008)

P. Dean et al.

The cerebellar microcircuit as an adaptive filter: experimental and computational evidence

Nat. Rev. Neurosci.

(2010)

Cited by (51)

Lactoferrin alleviates Western diet-induced cognitive impairment through the microbiome-gut-brain axis
2023, Current Research in Food Science
Lactoferrin (Lf) has been shown to benefit cognitive function in several animal models. To elucidate the underlying mechanisms, male C57BL/6J mice were randomly divided into the control (CON), Western-style diets (WD), lactoferrin (Lf), and Lf + antibiotics (AB) groups. The Lf group was intragastrically administered with Lf, and the Lf + AB group additionally drank a solution with antibiotics. After 16 weeks of intervention, Lf improved the cognitive function as indicated by behavioral tests. Lf also increased the length and curvature of postsynaptic density and upregulated the related protein expression, suggesting improved hippocampal neurons and synapses. Lf suppressed microglia activation and proliferation as revealed by immunofluorescence analysis. Lf decreased the serum levels of pro-inflammatory cytokines and downregulated their protein expressions in the hippocampus region. Lf also inhibited the activation of NF-κB/NLRP3 inflammasomes in the hippocampus. Meanwhile, Lf upregulated the expression of tight junction proteins, and increased the abundance of Bacteroidetes at phylum and Roseburia at genus, which are beneficial for gut barrier and cognitive function. The antibiotics eliminated the effects of long-term Lf intervention on cognitive impairment in the Lf + AB group, suggesting that gut microbiota participated in Lf action. Short-term Lf intervention (2 weeks) prevented WD-induced gut microbiota alteration without inducing behavioral changes, supporting the timing sequence of gut microbiota to the brain. Thus, Lf intervention alleviated cognitive impairment by inhibiting microglial activation and neuroinflammation through the microbiome-gut-brain axis.
Time dependent alteration of locomotor behavior in rat with acute liver failure induced cerebellar neuroinflammation and neuro-astroglial damage
2022, Journal of Chemical Neuroanatomy
Citation Excerpt :
In our TAA rats, the histological study of the cerebellum Purkinje layer demonstrated a progressive neuronal loss of such cells, with increased COX2 expression leading to suppose the presence of neuroinflammation. Hence, the cerebellum gained considerable attention due to its main role in motor learning behavior, while Purkinje neurons are considered as the only outputs of the cerebellar cortex and may contribute to the motor function(Lamont and Weber, 2012). Indeed, COX-2, inducible isoform of the family of cyclooxygenase enzymes, which catalyzes the conversion of arachidonic acid into prostaglandins(PGE2).
Hepatic encephalopathy (HE) is a neurophysiological syndrome secondary to acute or chronic liver failure. Studies showed that HE patients exhibit a deficit in motor coordination, which may result from cerebellar functional impairment. The aim of this study is to assess the time-dependent alteration of locomotor behavior and the glial and neuronal alteration in rat with acute HE induced chemically. The study was carried out in male Sprague-Dawley rats with thioacetamide (TAA) induced acute liver failure at different stages 12 h, 24 h and 36 h. Hepatic and renal functions were assessed via various biochemical and histopathological examinations, while the cerebellum and the midbrain were examined using histology and immunohistochemistry for tyrosine hydroxylase (TH), cyclooxygenase-2 (COX-2) and glial fibrillary acidic protein (GFAP). We used as well, the open field test and the Rotarod test for assessing the locomotor activity and coordination. Our data showed a progressive loss of liver function and a progressive alteration in locomotor behavior and motor coordination in acute HE rats. In the cerebellum, we noted an increase in the degeneration of cerebellar Purkinje neurons parallel to increased COX-2 immunoreactivity together with astrocytic morphology and density changes. Likewise, in substantia nigra pars compacta, TH levels were reduced. We showed through the current study, a progressive deterioration in locomotor behavior in acute HE rats, as a result of Purkinje neurons death and a deficient dopaminergic neurotransmission, together with the morpho-functional astroglial modifications involving the oxidative stress and neuroinflammation.
Impaired cerebellar plasticity and eye-blink conditioning in calpain-1 knock-out mice
2020, Neurobiology of Learning and Memory
Calpain-1 and calpain-2 are involved in the regulation of several signaling pathways and neuronal functions in the brain. Our recent studies indicate that calpain-1 is required for hippocampal synaptic plasticity, including long-term depression (LTD) and long-term potentiation (LTP) in field CA1. However, little is known regarding the contributions of calpain-1 to cerebellar synaptic plasticity. Low frequency stimulation (LFS, 5 Hz, 5 min)-induced LTP at parallel fibers to Purkinje cell synapses was markedly impaired in cerebellar slices from calpain-1 knock-out (KO) mice. Application of a selective calpain-2 inhibitor enhanced LFS-induced LTP in both wild-type (WT) and calpain-1 KO mice. Three protocols were used to induce LTD at these synapses: LFS (1 Hz, 15 min), perfusion with high potassium and glutamate (K-Glu) or dihydroxyphenylglycine (DHPG), a mGluR1 agonist. All three forms of LTD were impaired in calpain-1 KO mice. DHPG application stimulated calpain-1 but not calpain-2 in cerebellar slices, and DHPG-induced LTD impairment was reversed by application of a protein phosphatase 2A (PP2A) inhibitor, okadaic acid. As in hippocampus, BDNF induced calpain-1 activation and PH domain and Leucine-rich repeat Protein Phosphatase 1/suprachiasmatic nucleus oscillatory protein (PHLPP1/SCOP) degradation followed by extracellular signal-regulated kinase (ERK) activation, as well as calpain-2 activation leading to degradation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in cerebellar slices. The role of calpain-1 in associative learning was evaluated in the delay eyeblink conditioning (EBC). Calpain-1 KO mice exhibited significant learning impairment in EBC during the first 2 days of acquisition training. However, after 5 days of training, the percentage of conditioned responses (CRs) between calpain-1 KO and WT mice was identical. Both calpain-1 KO and WT mice exhibited typical extinction patterns. Our results indicate that calpain-1 plays critical roles in multiple forms of synaptic plasticity and associative learning in both hippocampus and cerebellum.
Cerebellar transcranial direct current stimulation modulates the effect of cerebellar transcranial magnetic stimulation on the excitability of spinal reflex
2020, Neuroscience Research
Citation Excerpt :
The influence of online or offline protocols on the effect of ctDCS is not unclear; therefore, further study may be needed on this topic (van Dun et al., 2016b). It is unclear whether the ctDCS affects the Purkinje fibers or other entities, such as parallel fibers (Lamont and Weber, 2012), granule cells, and basket cells (Ishikawa et al., 2014). The cerebellar folding influences polarization along the sulci (Rahman et al., 2014), indicating that the complexity of cerebellar structure causes hyperpolarization in some neurons while others may be depolarized simultaneously, leading to different global effects of ctDCS (Woods et al., 2016; van Dun et al., 2016b).
Cerebellar transcranial magnetic stimulation (C-TMS) facilitates the ipsilateral soleus H-reflex, which reflects the excitability of the spinal motoneuron pool. This study aimed to investigate whether this facilitation of the spinal motoneuron pool excitability by C-TMS is affected by cerebellar transcranial direct current stimulation (ctDCS) in a polarity-specific manner. Eleven healthy adults participated in this study. The H-reflex was measured from the right soleus muscle by electrical stimulation of the right tibial nerve. The conditioning TMS over the right cerebellum was delivered 110 ms before tibial nerve stimulation. The H-reflex ratio was calculated as conditioned/unconditioned H-reflex amplitude, and measured for pre- or post-anodal, cathodal, or sham right ctDCS, for 15 min with 2 mA. The results showed that the H-reflex ratio was significantly increased by anodal ctDCS, reduced by cathodal ctDCS, and not affected by sham ctDCS, indicating that the effect of C-TMS on the H-reflex is modulated by ctDCS in a polarity-specific manner. This implies that the effect of C-TMS on the spinal motoneuron pool is affected by the change in excitability of the cerebellum.
Acute alcohol and cognition: Remembering what it causes us to forget
2019, Alcohol
Addiction has been conceptualized as a specific form of memory that appropriates typically adaptive neural mechanisms of learning to produce the progressive spiral of drug-seeking and drug-taking behavior, perpetuating the path to addiction through aberrant processes of drug-related learning and memory. From that perspective, to understand the development of alcohol use disorders, it is critical to identify how a single exposure to alcohol enters into or alters the processes of learning and memory, so that involvement of and changes in neuroplasticity processes responsible for learning and memory can be identified early. This review characterizes the effects produced by acute alcohol intoxication as a function of brain region and memory neurocircuitry. In general, exposure to ethanol doses that produce intoxicating effects causes consistent impairments in learning and memory processes mediated by specific brain circuitry, whereas lower doses either have no effect or produce a facilitation of memory under certain task conditions. Therefore, acute ethanol does not produce a global impairment of learning and memory, and can actually facilitate particular types of memory, perhaps particular types of memory that facilitate the development of excessive alcohol use. In addition, the effects on cognition are dependent on brain region, task demands, dose received, pharmacokinetics, and tolerance. Additionally, we explore the underlying alterations in neurophysiology produced by acute alcohol exposure that help to explain these changes in cognition and highlight future directions for research. Through understanding the impact that acute alcohol intoxication has on cognition, the preliminary changes potentially causing a problematic addiction memory can better be identified.
Cellular calcium signaling in the aging brain
2019, Journal of Chemical Neuroanatomy
Aging in the biological system is an irreversible process. In the initial stages of lifespan aging improves survival skills of an organism while in the later stages aging reduce the survival skills. Aging is associated with changes in several cellular and molecular functions among which calcium signaling is a prominent one. Calcium signaling is essential for many vital functions of the brain and even minor impairments in calcium signaling can lead to deleterious consequences including neuronal death. Calcium signaling proteins are pursued as promising drug targets for many aging related diseases. This review attempts to summarize changes in calcium signaling in the brain as a result of aging.

View all citing articles on Scopus

View full text

ReviewThe role of calcium in synaptic plasticity and motor learning in the cerebellar cortex

Abstract

Highlights

Introduction

Section snippets

Basic circuit in the cerebellar cortex

The role of calcium in cell signaling

Purkinje cells

Insights from transgenic mouse models

Summary and concluding remarks

Acknowledgments

Cell

Math. Biosci.

Trends Neurosci.

Neuron

Neurosci. Lett.

FEBS Lett.

Neuropharmacology

Brain Res.

Neuron

Neuron

Neuron

Neuron

Neuron

Neuron

Neuron

Neurosci. Lett.

Prog. Neurobiol.

Neuron

Neuron

Neuron

Behav. Brain Res.

Neuron

Neuron

Neuron

Trends Neurosci.

Neuroscience

Neuron

Neuron

Prog. Neurobiol.

Brain Res.

Brain Res.

Neuron

Neuroscience

Neuropharmacology

GABAergic spill-over transmission onto hippocampal mossy fibre boutons

J. Neurosci.

Submillisecond precision of the input–output transformation function mediated by fast sodium dendritic spikes in basal dendrites of CA1 pyramidal neurons

J. Neurosci.

Activity-evoked capacitative Ca2+ entry: implications in synaptic plasticity

J. Neurosci.

Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways

Science

Cerebellar climbing fibres modulate simple spikes in Purkinje cells

J. Neurosci.

A role for protein phosphatases 1, 2A, and 2B in cerebellar long-term potentiation

J. Neurosci.

A synaptic model of memory: long-term potentiation in the hippocampus

Nature

Cortex is driven by weak but synchronously active thalamocortical synapses

Science

Quantal events shape cerebellar interneuron firing

Nat. Neurosci.

Integration of quanta in cerebellar granule cells during sensory processing

Nature

Bidirectional parallel fibre plasticity in the cerebellum under climbing fibre control

Neuron

Metabotropic glutamate receptors: electrical and chemical signaling properties

Neuroscientist

Selective amplification of neocortical neuronal output by fast prepotentials in vivo

Cereb. Cortex

The critical role of Golgi cells in regulating spatio-temporal integration and plasticity at the cerebellum input stage

Front. Neurosci.

The origin of the complex spike in cerebellar Purkinje cells

J. Neurosci.

The cerebellar microcircuit as an adaptive filter: experimental and computational evidence

Nat. Rev. Neurosci.

Review
The role of calcium in synaptic plasticity and motor learning in the cerebellar cortex

Activity-evoked capacitative Ca²⁺ entry: implications in synaptic plasticity