Cerebellum parallel fibers

At the same time that the motor neurons send signals to the muscles, branches travel into other parts of the brain including the olivary nuclei, which send neurons into the cerebellum. The cerebellum acts as a kind of computer needed for fine tuning of the impulses to the muscles. Injury to the cerebellum leads to difficulty in finely coordinated motions. Input to the Purkinje cells arises from the climbing fibers, which originate in the inferior olive of the brain stem. Each climbing fiber activates a single Purkinje cell, but the dendrites of each Purkinje cell also form as many as 200,000 different synapses with parallel fibers that run across the cortex of the cerebellum (Fig. 30-15). 

PKA-dependent long-term potentiation and depression was initially discovered in the mossy-fiber synapses of the hippocampus, and later demonstrated in parallel fiber synapses of the cerebellum and corticothalamic synapses of the forebrain (Malenka and Siegelbaum, 2001). This widespread form of plasticity does not involve changes in Ca2+-influx, but operates via a direct increase or decrease, respectively, of the amount of vesicle exocytosis that can be triggered by a given Ca2+-signal. Interestingly, this form of plasticity appears to depend on the interaction... 

Hansel C, Linden DJ, D Angelo E (2001) Beyond parallel fiber LTD the diversity of synaptic and non-synaptic plasticity in the cerebellum. Nat Neurosci 4 467-75 Hao J, Michalek C, Zhang W et al (2006) Regulation of cardiomyocyte signaling by RGS proteins differential selectivity towards G proteins and susceptibility to regulation. J Mol Cell Cardiol 41 51-61... 

McGee AW, Topinka JR, Hashimoto K, Petralia RS, Kakizawa S, et al. 2001. PSD-93 knock-out mice reveal that neuronal MAGUKs are not required for development or function of parallel fiber synapses in cerebellum. J. Neurosci. 21 3085-91... 

The parallel fibers — the axons of granule cells — constitute the third major excitatory fiber system in the cerebellum. The parallel fibers establish synapses with Purkinje cell spines as well as with dendritic stems of intemeurons (Palay and Chan-Palay, 1974). Several lines of evidence point to glutamate as the most likely transmitter in the parallel fiber system. 

Landsend AS, Amiry-Moghaddam M, Matsubara A, Bergersen L, Usami S, Wentbold RJ, Ottersen OP (1997) Differential localization of glutamate receptors in the rat cerebellum coexpression with AMPA receptors in parallel fiber-spine synapses and absence from climbing fiber-spine synapses. J Neurosci /7 834 842. 

Fig. 6. Summary histogram of development of glutamate receptors at parallel [postnatal day 10 (PI0) to adult] and climbing (P2 to adult) fiber synapses on Purkinje cells of the cerebellum. Note especially the peak in immunogold labeling of the delta receptors at PI0-PI4 in climbing fiber synapses (cO, the peaks of the AMPA receptors (GluR2, GluR2/3 antibodies) at P2-P5, and the inverse patterns of peaks for parallel fiber synapses (pf) and climbing fiber synapses in adults for AMPA versus delta receptors. Modified from Zhao et al. (1998).

In the adult cerebellum, as noted above, parallel fiber synapses have abundant delta receptors, while delta receptors are rare or absent from climbing fiber synapses. AMPA receptors are found at both excitatory synapse populations but are more abundant at climbing fiber synapses. In the first postnatal week, presumptive climbing fiber synapses have high... 

Fig. 7. Granule cells and parallel fibers after an injection of biocytin in lobule X of the cerebellum of the rat. A. Biocytin labelled granule cell. B. Golgi-impregnated granule cells and parallel fibers in transverse section. Cajal (1911). C. biocytin injection site in granular layer and labelled parallel fibers in molecular layer. D. bifurcation site of labelled parallel fibers. E. labelled varicose parallel fibers. Abbreviations A molecular layer B granular layer C white matter a granule cell axon b bifurcation of granule cell axon d Purkinje cell f Purkinje cell axon g granular layer I injection site m molecular layer. Bars in A = 12 /tm, in C = 500 nva, in D and E = 50 //m. Courtesy of Dr. T.J.H. Ruigrok.

Fig. 48. Electron micrograph of the synaptic distribution of immunoreactivity for the GluRl subunit of the AMPA receptor in rat cerebellum as detected by an antibody against the carboxy-terminal (intracellular) region of GluRl. A. A spine (s) emerging from a Purkinje cell dendrite (Pd) establishes an immunopositive type 1 synapse (solid arrows) with a parallel fiber terminal (pft). Intra-cellular immunoreactivity is present inside Bergmann glial cell processes along dendritic elements (e.g., open arrow). B. The peroxidase reaction end-product labels the postsynaptic density (psd) at the intracellular face of the postsynaptic membrane (pom) and not the synaptic cleft between the presyaptic (pem) and postsynaptic (pom) membranes. Scale bars in A = 0.5 /xm, in B = 0.1 jum. Baude et al. (1994).

NA. A heavy plexiform innervation of the granular layer by thin varicose axons and parallel fiber-like fluorescence in the molecular layer was also found in chicken cerebellum. The parent fibers in the cerebellar white matter were concentrated in two parasagittal bundles (Mugnaini and Dahl, 1975). 

Summarizing it appears that the cellular and regional distribution of muscarine receptors in the cerebellum is different between different species. Golgi cells and subpopulations of mossy fibers seem to express muscarine receptors most constantly. An interesting aspect about the presence of muscarine receptors in parallel fibers in rat and rabbit, is that the lobular distribution of m2-containing parallel fibers, is the same as that of ChAT-positive mossy fiber rosettes (see above). This raises the possibility that muscarine m2 receptor are specifically expressed by those granule cells that are innervated by cholinergic mossy fibers. If this proves to be true, this would imply that there... 

Fig. 146. Parasagittal section of the rat cerebellar vermis immunostained with antiserum to calretinin. Folia are labelled with roman numerals according to Larsell. The pattern of immunoreactivity in the nodulus (lobule X) and portion of the ventral uvula (lobule IXd) differs from that in the other vermal folia. While in most of the vermis weak immunoreactivity is present in granule cell bodies within the granular layer and in parallel fibers within the molecular layer, in the folia X and IXd of the vestibulo-cerebellum the immunoreaction product is largely localized in unipolar brush cells and mossy fibers, MN, medial cerebellar nucleus. Bar = 1 mm. Floris et al. (1994).

Eccles JC, Elinas R, Sasaki K (1966c) Parallel fiber stimulation and responses induced thereby in the Purkinje cells of the cerebellum. Exp. Brain Res., I, 17-39. 

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