Section IIILong-term potentiation of synaptic transmission at the mossy fiber–granule cell relay of cerebellum
Section snippets
The cerebellum and the mossy fiber–granule cell relay
The cerebellum is a brain structure of primary importance for the coordination of movement, and is also probably involved in processing higher brain functions (Ghez and Thach, 2003). The basic architecture of the cerebellar circuitry is well known (Eccles et al., 1967; Ito, 1984). The cerebellum receives two main inputs through mossy fibers (mfs) and climbing fibers (cfs). Cfs originate in the inferior olivary nucleus and innervate Purkinje cells (PCs). Mfs are the largest cerebellar afferent
Mossy fiber–granule cell long-term potentiation (LTP)
Marr (1969) explicitly negated the possibility that mf–GrC synaptic weights could be modified by activity. He noted that ‘sooner or later all weights would be saturated ’ so that plasticity would not be useful. Thus, Marr’s model did not include any mf–GrC synaptic plasticity, although the subsequent extension due to Albus (1971) was more permissive. However, the observation that mf discharge consists of high-frequency bursts (Kase et al., 1980) and that GrCs express NMDA receptors, which
Functional consequences of mossy fiber–granule cell LTP
The cerebellum is thought to operate in feed-forward mode anticipating the corrections needed to regulate complex sequences of movements (Ghez and Thach, 2003). As every feed-forward device, the cerebellum needs to store information to be used in a predictive manner. No surprise therefore that the cerebellar circuitry expresses mechanisms for learning and memory. As proposed by Marr (1969), a major form of plasticity occurs at the pf-PC synapse, allowing heterosynaptic depression when a motor
Conclusions
Although several aspects remain to be investigated, mf–GrC LTP provides a wide substrate for information storage in the cerebellum. In the rat cerebellum, there are 1011 GrCs and four times as many mf–GrC synapses. Mathematical models have suggested that mf–GrC LTP improves mutual information transfer and regulates codon representation (Schweighofer et al., 2000; Philipona et al., 2003). Moreover, a preliminary investigation suggests a role in regulating neurotransmission dynamics (Nieus et
Acknowledgements
Supported by European Community grants IST-2001-35271 and QLG3-CT-2001-02256, by MIUR and INFM of Italy.
References (53)
A theory of cerebellar function
Math. Biosci.
(1971)- et al.
Nitric oxide acts directly in the presynaptic terminal to produce long-term potentiation in cultured hippocampal neurons
Cell
(1996) - et al.
Embarassed, but not depressed: eye opening lessons for cerebellar learning
Neuron
(2002) - et al.
Different proportions of N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor currents at the mossy fibre–granule cell synapse of developing rat cerebellum
Neuroscience
(1993) - et al.
Spillover of glutamate onto synaptic AMPA receptors enhances fast transmission at a cerebellar synapse
Neuron
(2002) - et al.
LTP of AMPA and NMDA receptor-mediated signals: evidence for presynaptic expression and extrasynaptic glutamate spillover
Neuron
(1996) - et al.
Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo
Cell
(1998) - et al.
Long-term potentiation of intrinsic excitability at the mossy fiber–granule cell synapse of rat cerebellum
J. Neurosci.
(2000) - et al.
Presynaptic mechanism for long-term potentiation in the hippocampus
Nature
(1990) - et al.
Localization of nitric oxide synthase indicating a neural role for nitric oxide
Nature
(1990)
A synaptic model of memory: long-term potentiation in the hippocampus
Nature
Maturation of EPSCs and intrinsic membrane properties enhances precision at a cerebellar synapse
J. Neurosci.
Synaptic excitation of individual rat cerebellar granule cells in situ: evidence for the role of NMDA receptors
J. Physiol. (Lond.)
Evidence for NMDA and mGlu receptor-dependent long-term potentiation of mossy fibre–granule cell transmission in rat cerebellum
J. Neurophysiol.
Evidence for increased neurotransmitter release during cerebellar mossy fiber–granule cell LTP
Neurosci. Soc. Abs.
A new functional role for cerebellar long-term depression
Prog. Brain Res.
Serotonin-driven long-range inhibitory connections in the cerebellar cortex
J. Neurosci.
The Cerebellum as a Neuronal Machine
Anatomy and electrophysiology of fast central synapses lead to a structural model for long-term potentiation
Physiol. Rev.
Role of calcium binding proteins in the control of cerebellar granule cell neuronal excitability: experimental and modeling studies
Progr. Brain. Res
Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain
Nature
Silent synapses in the developing hippocampus: lack of functional AMPA receptors or low probability of glutamate release?
Proc. Nat. Acad. Sci. (USA)
The cerebellum
Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum
Nature Neurosci.
Oscillatory activity in cerebellar hemispheres on unrestrained rats
J. Neurophysiol.
Cited by (44)
Intracellular Ca<sup>2+</sup> thresholds for induction of excitatory long-term depression and inhibitory long-term potentiation in a cerebellar Purkinje neuron
2016, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Secondly, mutant mice presumably defective in the last step of LTD expression, which is internalization of AMPA-type ionotropic glutamate receptors and thus seems to affect only LTD, show normal motor learning [9]. In addition, several types of synaptic plasticity other than LTD at parallel fiber – Purkinje neuron synapses such as long-term potentiation (LTP) at the same synapses, RP at inhibitory interneuron – Purkinje neuron synapses, LTP and LTD at parallel fiber – inhibitory interneuron synapses, LTP at mossy fiber –granule cell synapses, LTP in the cerebellar nuclei etc. have been reported [30,35–39]. With such information, involvement of plasticity mechanisms other than parallel fiber – Purkinje neuron LTD in motor learning has been proposed [2,10,11].
Acute neuregulin-1 signaling influences AMPA receptor mediated responses in cultured cerebellar granule neurons
2012, Brain Research BulletinCitation Excerpt :An alternate explanation for the NRG1-induced decrease in AMPAR-mEPSC frequency in CGCs is that NRG1 influences vesicle release probability. For example, activation of postsynaptic ErbB4 could affect presynaptic function by regulating the synthesis of retrograde signaling molecules such as nitric oxide, that is believed to enhance presynaptic vesicle release at mossy fiber-granule cell synapses [7]. Consistent with this idea, NRG1 may affect the function of nNOS in CGCs through a mechanism that involves activation of MAP kinase [16]; however, NRG1 has not been shown to affect neurotransmitter release in CGCs.
Restoring a Loss of Mossy Fiber Plasticity in a Model of Fragile X Syndrome
2023, Essentials of Cerebellum and Cerebellar Disorders: A Primer For Graduate Students, Second EditionCerebellar Granule Cell
2021, Handbook of the Cerebellum and Cerebellar Disorders: Second Edition: Volume 3Effect of Dopamine on The Interdependent Functioning of The Cerebellum, Basal Ganglia and Neocortex (A Hypothetical Mechanism)
2021, Uspekhi Fiziologicheskikh Nauk