Pattern formation in the cerebellar cortex.

The cerebellar cortex is subdivided rostrocaudally and mediolaterally into a reproducible array of zones and stripes. This makes the cerebellum a valuable model for studying pattern formation in the vertebrate central nervous system. The structure of the adult mouse cerebellar cortex and the series of embryological events that generate the topography are reviewed.     

Aftereffect phenomena in neurons of the cerebellar cortex

The reactions of Purkinje cells (PC) of the cerebellar cortex during electrocutaneous stimulation of one of the extremities with different frequencies (from one stimulus in 10 sec to one to five stimuli per sec) were studied in experiments on cats. It was shown that the reactions to the first and subsequent stimuli were different. This indicates the presence of an aftereffect from the first stimulus. It is assumed that the variability of the responses of PC to infrequent stimuli is connected with changes in their functional state which develop in response to "spontaneous" cerebellopetal impulses, as well as to circulation of excitation in intracerebellar circuits. With an increase in the frequency of the stimuli, the changes in excitability induced by previous peripheral stimuli, not only in the reacting PC, but also in the whole neuronal network of the corresponding cerebellopetal pathway, evidently acquire paramount importance. The absence of a direct relationship between strong peripheral stimulation and the degree of the reactions of the PC may be due to the involvement of intermediate neurons both of the exciting and inhibitory type in the transmission of impulses at the level of the cerebellar cortex.N. I. Pirogov Vinnitsa Medical Institute. Translated from Neirofiziologiya, Vol. 2, No. 6, pp. 573–580, November–December, 1970.     

Pre and post synaptic NMDA effects targeting Purkinje cells in the mouse cerebellar cortex

N-methyl-D-aspartate (NMDA) receptors are associated with many forms of synaptic plasticity. Their expression level and subunit composition undergo developmental changes in several brain regions. In the mouse cerebellum, beside a developmental switch between NR2B and NR2A/C subunits in granule cells, functional postsynaptic NMDA receptors are seen in Purkinje cells of neonate and adult but not juvenile rat and mice. A presynaptic effect of NMDA on GABA release by cerebellar interneurons was identified recently. Nevertheless whereas NMDA receptor subunits are detected on parallel fiber terminals, a presynaptic effect of NMDA on spontaneous release of glutamate has not been demonstrated. Using mouse cerebellar cultures and patch-clamp recordings we show that NMDA facilitates glutamate release onto Purkinje cells in young cultures via a presynaptic mechanism, whereas NMDA activates extrasynaptic receptors in Purkinje cells recorded in old cultures. The presynaptic effect of NMDA on glutamate release is also observed in Purkinje cells recorded in acute slices prepared from juvenile but not from adult mice and requires a specific protocol of NMDA application.     

The myelination of the cerebellar cortex in the cat

Summary The myelination of the cerebellar cortex of the cat was investigated in 61 cats aged from 3 hrs post partum to two and a half years. The first myelinated fibers appear at the time of birth in the central medullary ray. Before the onset of myelination, all fibers reach a critical diameter of about 1 m. About the 14th day of life the number of oligodendrocytes in the prospective white matter increases markedly. Thereafter, the oligodendrocytes invade the inner granular layer. It therefore seems that the myelination of the cerebellar cortex proceeds from the central medullary ray towards the granular layer. At the 60th day of postnatal life, most of the afferent and efferent fiber systems are myelinated. These findings are discussed in relation to the development of function and the maturation of the electrical activity of the cerebellar circuit.Dedicated to Prof. Dr. H. Leonhardt in honour of his 60th birthdaySupported by the Deutsche Forschungsgemeinschaft (La 184/3)     

High-frequency network oscillations in cerebellar cortex

Both cerebellum and neocortex receive input from the somatosensory system. Interaction between these regions has been proposed to underpin the correct selection and execution of motor commands, but it is not clear how such interactions occur. In neocortex, inputs give rise to population rhythms, providing a spatiotemporal coding strategy for inputs and consequent outputs. Here, we show that similar patterns of rhythm generation occur in cerebellum during nicotinic receptor subtype activation. Both gamma oscillations (30-80 Hz) and very fast oscillations (VFOs, 80-160 Hz) were generated by intrinsic cerebellar cortical circuitry in the absence of functional glutamatergic connections. As in neocortex, gamma rhythms were dependent on GABA(A) receptor-mediated inhibition, whereas VFOs required only nonsynaptically connected intercellular networks. The ability of cerebellar cortex to generate population rhythms within the same frequency bands as neocortex suggests that they act as a common spatiotemporal code within which corticocerebellar dialog may occur.     

Plausible function of Golgi cells in the cerebellar cortex

The function of Golgi cells in the cerebellar cortex is quantitatively examined in consideration of the nonlinear input-output characteristics and convergence and divergence numbers of cells. It is strongly suggested that the two signal paths to Golgi cells have different function. The feed-forward path will have the same function as assumed in the previous theories of the cerebellar cortex, that is, to keep the firing rate of granule cells approximately constant over considerable variation in the firing rate of mossy fibers. The feedback path will, on the other hand, have a new function which has not been assumed in the previous theories. The function is to cause oscillation of the firing rate of granule cells for stationary mossy fiber inputs. The assumption of the new function enables us to explain cerebellar function to keep stationary posture.     

The development of molecular compartmentation in the cerebellar cortex

The cerebellum is subdivided into hundreds of discrete modules defined by their connectivity and molecular signatures. Cerebellar compartmentation arises very early in development through the formation of multiple populations of chemically distinct Purkinje cells that migrate in a coordinated fashion to form parasagittal bands of cells. Different Purkinje cell bands are then innervated by discrete subpopulations of cerebellar afferents. Because of its stereotyped and strikingly beautiful organization the cerebellum is an excellent model in which to explore genetic/epigenetic aspects of pattern formation in the central nervous system.     

Neurotrophic effects of extracellular guanosine

Central nervous system (CNS) astrocytes release guanosine extracellularly, that exerts trophic effects. In CNS, extracellular guanosine (GUO) stimulates mitosis, synthesis of trophic factors, and cell differentiation, including neuritogenesis, is neuroprotective, and reduces apoptosis due to several stimuli. Specific receptor-like binding sites for eGUO in the nervous system may mediate its effects through both MAP kinase and PI3-kinase signalling pathways. Extracellular guanine (eGUA) also exerts several effects; the trophic effects of eGUO are likely regulated by conversion of eGUO to eGUA by a membrane located purine nucleoside phosphorylase (ecto-PNP) and by conversion of eGUA to xanthine by guanine deaminase.     

Two types of granular cells in the cerebellar cortex

We recorded the activity of two types of granular cells in the rostral folia of the paramedial lobe (the projection region of the front legs) of the cerebellar cortex in cats immobilized by administration of ditiline; these cells differed in their receptive fields, the characteristics of their reaction to single stimulation of somatic nerves, and the character of their background activity. The granular cells of the first type were excited only when the nerves of the front legs were stimulated (reacting with 1–3 impulses with a latent period of 8–20 msec) and were inhibited between 20–50 and 70–180 msec after stimulation of the nerves of any leg. The cells of the second type responded with volleys of 3–6 impulses with a latent period of 20–40 msec to stimulation of the nerves of all four legs. Comparison of the reactions of the granular cells and other neurons of the cerebellar cortex showed that the cells of the first type cause excitation of the Purkinje and Golgi cells and the neurons of the molecular layer. The granular cells of the second type have an excitatory effect on the Golgi cells. The differences in the reactions of the two types of granular cells result from the fact that they are selectively innervated by the mossy fibers of different afferent pathways. Comparison with the data in the literature enables us to surmise that the fibers of the cuneocerebellar tract terminate at granular cells of the first type, while the reticular fibers terminate at cells of the second type.Institute of Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 1, No. 2, pp. 167–176, September–October, 1969.     

Cytospectrophotometric study of GABA-transaminase in the rat cerebellar cortex

Modification of the histochemical method for detection of GABA-transaminase activity is suggested. Optimal concentrations of the substrates and cofactors are chosen on the basis of kinetic study of the enzymatic reaction in the cryostat sections of the rat cerebellar cortex by the quantitative microspectrophotometric method. The method is intended for the quantitative histochemical analysis of GABA-transaminase activity in the brain sections.     

Causes and consequences of oscillations in the cerebellar cortex

Cerebellar high-frequency oscillations have been observed for many decades, but their underlying mechanisms have remained enigmatic. In this issue of Neuron, two papers indicate that specific intrinsic mechanisms in the cerebellar cortex contribute to the generation of these oscillations. Middleton et al. show that GABA(A) receptor activation and nonchemical transmission are required for nicotine-dependent oscillations at 30-80 Hz and 80-160 Hz, respectively, while de Solages et al. provide evidence that recurrent inhibition by Purkinje cells is essential for oscillations around 200 Hz.     

Immunocytochemical localization of the prostaglandin-forming cyclooxygenase in the cerebellar cortex

An indirect immunocytofluorescence technique was used to examine the distribution of the prostaglandin-forming cyclooxygenase in the cerebellar cortex of the pig, guinea, rat, mouse, cow, rabbit and sheep. Cyclooxygenase antigenicity was detected (a) in the cell bodies of Bergman glial cells in the Purkinje cell layer of the porcine, ovine and bovine cerebellar cortex; (b) in small arterioles throughout the cerebellar cortex in the sheep and cow; and (c) in the endothelial cells of large arteries in all the species examined. No cyclooxygenase-positive staining was apparent in neuronal cell bodies of granule, basket, stellate or Purkinje cells. Our results establish that prostaglandin endoperoxides can be synthesized by the arterial vasculature and at least certain glial cells in the central nervous system.