C3 Zone Research Articles

Transmission of Predictable Sensory Signals to the Cerebellum via Climbing Fiber Pathways Is Gated during Exploratory Behavior.

Pathways arising from the periphery that target the inferior olive [spino-olivocerebellar pathways (SOCPs)] are a vital source of information to the cerebellum and are modulated (gated) during active movements. This limits their ability to forward signals to climbing fibers in the cerebellar cortex. We tested the hypothesis that the temporal pattern of gating is related to the predictability of a sensory signal. Low-intensity electrical stimulation of the ipsilateral hindlimb in awake rats evoked field potentials in the C1 zone in the copula pyramidis of the cerebellar cortex. Responses had an onset latency of 12.5 ± 0.3 ms and were either short or long duration (8.7 ± 0.1 vs 31.2 ± 0.3 ms, respectively). Both types of response were shown to be mainly climbing fiber in origin and therefore evoked by transmission in hindlimb SOCPs. Changes in response size (area of field, millivolts per millisecond) were used to monitor differences in transmission during rest and three phases of rearing: phase 1, rearing up; phase 2, upright; and phase 3, rearing down. Responses evoked during phase 2 were similar in size to rest but were smaller during phases 1 and 3, i.e., transmission was reduced during active movement when self-generated (predictable) sensory signals from the hindlimbs are likely to occur. To test whether the pattern of gating was related to the predictability of the sensory signal, some animals received the hindlimb stimulation only during phase 2. Over ∼10 d, the responses became progressively smaller in size, consistent with gating-out transmission of predictable sensory signals relayed via SOCPs.SIGNIFICANCE STATEMENT A major route for peripheral information to gain access to the cerebellum is via ascending climbing fiber pathways. During active movements, gating of transmission in these pathways controls when climbing fiber signals can modify cerebellar activity. We investigated this phenomenon in rats during their exploratory behavior of rearing. During rearing up and down, transmission was reduced at a time when self-generated, behaviorally irrelevant (predictable) signals occur. However, during the upright phase of rearing, transmission was increased when behaviorally relevant (unpredictable) signals may occur. When the peripheral stimulation was delivered only during the upright phase, so its occurrence became predictable over time, transmission was reduced. Therefore, the results indicate that the gating is related to the level of predictability of a sensory signal.

Control Effect of a Large Geological Discontinuity on the Seismic Response and Stability of Underground Rock Caverns: A Case Study of the Baihetan #1 Surge Chamber

In this paper, the seismic stability of the #1 surge chamber of the Baihetan hydropower plant, which is influenced by a large dominating geological discontinuity [the interlayer shear weakness zone (ISWZ) C2)], is studied. An advanced, nonlinear, continuously yielding (CY) model was adopted to describe the complex mechanical properties of ISWZ C2. This model considers a power function type, normal stress dependent behavior and the progressive damage that occurred during shear tests. The applicability of the CY model is proved via a comparison with field test results and the theoretical solution. Verification work was conducted in 3DEC code to show that the 3DEC software is suitable for implementing this model. Three ground motion waveforms were utilized to conduct a seismic analysis of the #1 surge chamber after a special response spectrum matching process. The seismic analysis confirmed the control effect of ISWZ C2 on the seismic stability of the cavern. The majority of the cavern’s seismic displacement consists of elastic body movement, while the plastic deformation is relatively limited. Further, most of the deformations were caused by the contact deformation of C2. For the contact deformation of C2, the magnitude of permanent shear deformation is larger than that of the normal deformation. The magnitude of permanent shear deformation is more notable along the strike direction of C2, and the permanent normal displacement n of C2 mainly occurs along the dip direction of C2. Finally, the seismic stability of the cavern is assessed via the overload method. The seismic safety factor of the cavern is approximately 2–3.

Applications of chemostratigraphy in Middle Jurassic unconventional reservoirs in eastern Saudi Arabia

ABSTRACT The following study was undertaken on inorganic geochemical data acquired for 1,032 core and cuttings samples taken from Middle Jurassic and Upper Jurassic sediments encountered in five wells in eastern Saudi Arabia. The study sections extend from the upper part of the Middle Jurassic Dhruma Formation to the base of the Upper Jurassic Arab Formation, though the principal focus was on the intervening Hanifa and Tuwaiq Mountain formations where potential unconventional hydrocarbon reservoirs have been encountered. The principal objective of the study was to produce a chemostratigraphic framework for these wells. A secondary aim was to utilize the geochemical data to recognize organic-rich zones and seals. The study sections mainly comprise limestones, argillaceous limestones and calcareous mudrocks, with the latter lithologies being more abundant in the Tuwaiq Mountain and Hanifa formations. Although ICP-OES (Inductively Coupled Plasma–Optical Emission Spectrometry) and ICP-MS (Inductively Coupled Plasma–Mass Spectrometry) were used to acquire data for 50 elements, the chemostratigraphic framework is based on changes in the following ‘key’ elements and ratios: Nb/Cr, Zr/Nb, Zr/Cr, Cr/Th, Cr/Ta, La/Lu, Zr/Yb, Nb/Ti and Ti/U. Variations in these parameters are dependent on changes in source/provenance, reflecting increases or decreases in the abundances of particular detrital heavy minerals. The framework comprises a hierarchical order of 5 zones, 10 subzones and 8 divisions. The zones are labeled C0, C1, C2, C3 and C4 in ascending stratigraphic order, with C2, C3 and C4 being divided into subzones. Further divisions are also recognized in some subzones. Zones C1, C2, C3 and C4 are correlative between all five wells, with the absence of C0 in three of the wells, probably explained by the existence of this zone below the present sampling intervals of these wells. Unlike most zones, some of the subzones/divisions are not identified in all wells. This is mostly explained by local variations in provenance being responsible for the presence of some subzones/divisions in certain wells but not others. In other instances the absence of particular subzones and divisions may have resulted from localized erosion/non-deposition. Lithostratigraphic boundaries are relatively easy to place in wells 1, 2 and 3 where there are similar changes in e-log response in all three study sections. However, this does not hold true for wells 4 and 5 where e-log trends are more or less obvious. In these wells it has been necessary to utilize chemostratigraphy in combination with much more subtle increases/decreases in e-log trends to identify these boundaries. In addition to enabling the placement of lithostratigraphic boundaries in wells 4 and 5, it is possible to use chemostratigraphy to produce a correlation scheme of much higher resolution than was possible by employing lithostratigraphy. For example, The Dhruma Formation was previously defined as a single lithostratigraphic unit but a fourfold chemostratigraphic zonation of this formation is now proposed for wells 1 and 2 (i.e. zones C0, C1, subzone C2-1, division C2-2a which occur in ascending order). By comparing profiles plotted for U, Mo and TOC it is possible to identify units in which there is a relatively high proportion of organic matter. Sediments producing high values of these parameters may be considered potential unconventional reservoirs, with the most organic-rich zones present in wells 1 and 2. Potential seals have been identified above the ‘reservoir’ sections of these two wells. These produce elevated values of Al and K, inferring an abundance of clay minerals which may prevent or reduce the propagation of induced fractures during future ‘fracking’ operations conducted in the vicinity of these wells.

Applications of chemostratigraphy in Cretaceous sediments encountered in the North Central Rub’ al-Khali Basin, Saudi Arabia

The following study was undertaken on inorganic geochemical data acquired for 832 core and cuttings samples taken from Cretaceous sediments encountered in 11 wells in the North Central Rub’ al-Khali Basin, Saudi Arabia. The study sections extend from Khafji Member at the base of the Wasia Formation to the basal part of the Aruma Formation. The principal objective of the study was to produce a chemostratigraphic scheme for these wells, though a comparison was also made with a previous lithostratigraphic scheme.Although ICP–OES (Inductively Coupled Plasma–Optical Emission Spectrometry) and ICP–MS (Inductively Coupled Plasma–Mass Spectrometry) were used to acquire data for 50 elements, the chemostratigraphic scheme is based on changes in the following ‘key’ elements and ratios: Ca, Al, Zr, P/Y, Zr/P, Zr/Y, Zr/Nb, Mo and Zr. The scheme comprises a hierarchical order of five zones, 18 subzones and four divisions, with the zones labelled C1, C2, C3, C4 and C5 in ascending stratigraphic order. The definition of these zones are mainly based on changes in Ca and Al reflecting variations in bulk lithology as a response to changes in base level. Zone C1 is dominated by elevated Al and low Ca concentrations and represents calcareous mudrocks deposited in a lagoonal–prodelta environment. An increase in base level led to the formation of highly calcareous rudistic limestones deposited in a shallow marine environment, with a further increase in base level resulting in the deposition of calcareous mudrocks with high Al values in zone C3. Zone C4 comprises rudistic limestones (with elevated Ca and low Al) deposited in shallow marine conditions, while C5 is dominated by calcareous mudrocks and argillaceous limestones deposited in a prodeltaic paleoenvironment. Although the definition of zones mainly relates to changes in base level/bulk lithology, more subtle changes in provenance are modelled using the P/Y, Zr/P, Zr/Y and Zr/Nb ratios which are used to define most subzones and divisions. Variations in this ratio are almost entirely dependent on changes in source/provenance.Although all of the zones and most of the subzones are correlative between the study wells it is noted that different criteria are used to define the zone C2 and C4 subzones in the eastern and western wells of the study area. This suggests that separate sediment sources were responsible for the delivery of clastic material to these carbonate ‘reefs’ during the deposition of these subzones.One important conclusion from this study is that there are close links between the chemostratigraphic and lithostratigraphic correlations but the former offers a much higher level of resolution.

Systematic regional variations in Purkinje cell spiking patterns.

In contrast to the uniform anatomy of the cerebellar cortex, molecular and physiological studies indicate that significant differences exist between cortical regions, suggesting that the spiking activity of Purkinje cells (PCs) in different regions could also show distinct characteristics. To investigate this possibility we obtained extracellular recordings from PCs in different zebrin bands in crus IIa and vermis lobules VIII and IX in anesthetized rats in order to compare PC firing characteristics between zebrin positive (Z+) and negative (Z−) bands. In addition, we analyzed recordings from PCs in the A2 and C1 zones of several lobules in the posterior lobe, which largely contain Z+ and Z− PCs, respectively. In both datasets significant differences in simple spike (SS) activity were observed between cortical regions. Specifically, Z− and C1 PCs had higher SS firing rates than Z+ and A2 PCs, respectively. The irregularity of SS firing (as assessed by measures of interspike interval distribution) was greater in Z+ bands in both absolute and relative terms. The results regarding systematic variations in complex spike (CS) activity were less consistent, suggesting that while real differences can exist, they may be sensitive to other factors than the cortical location of the PC. However, differences in the interactions between SSs and CSs, including the post-CS pause in SSs and post-pause modulation of SSs, were also consistently observed between bands. Similar, though less strong trends were observed in the zonal recordings. These systematic variations in spontaneous firing characteristics of PCs between zebrin bands in vivo, raises the possibility that fundamental differences in information encoding exist between cerebellar cortical regions.

Changes in complex spike activity during classical conditioning

The cerebellar cortex is necessary for adaptively timed conditioned responses (CRs) in eyeblink conditioning. During conditioning, Purkinje cells acquire pause responses or “Purkinje cell CRs” to the conditioned stimuli (CS), resulting in disinhibition of the cerebellar nuclei (CN), allowing them to activate motor nuclei that control eyeblinks. This disinhibition also causes inhibition of the inferior olive (IO), via the nucleo-olivary pathway (N-O). Activation of the IO, which relays the unconditional stimulus (US) to the cortex, elicits characteristic complex spikes in Purkinje cells. Although Purkinje cell activity, as well as stimulation of the CN, is known to influence IO activity, much remains to be learned about the way that learned changes in simple spike firing affects the IO. In the present study, we analyzed changes in simple and complex spike firing, in extracellular Purkinje cell records, from the C3 zone, in decerebrate ferrets undergoing training in a conditioning paradigm. In agreement with the N-O feedback hypothesis, acquisition resulted in a gradual decrease in complex spike activity during the conditioned stimulus, with a delay that is consistent with the long N-O latency. Also supporting the feedback hypothesis, training with a short interstimulus interval (ISI), which does not lead to acquisition of a Purkinje cell CR, did not cause a suppression of complex spike activity. In contrast, observations that extinction did not lead to a recovery in complex spike activity and the irregular patterns of simple and complex spike activity after the conditioned stimulus are less conclusive.

Spino‐olivary projections in the rat are anatomically separate from postsynaptic dorsal column projections

The gracile nucleus (GN) and lateral part of rostral dorsal accessory olive (rDAO) are important relays for indirect, postsynaptic dorsal column, and direct ascending pathways, respectively, that terminate as climbing fibers in the “hindlimb-receiving” parts of the C1 and C3 zones in the cerebellar cortex. While the spinal cells of origin of that project to GN and rDAO are from largely separate territories in the spinal cord, previous studies have indicated that there could be an area of overlap between these two populations in the medial dorsal horn. Given the access of these two ascending tracts to sensory (thalamic) versus sensorimotor (precerebellar) pathways, the present study therefore addresses the important question of whether or not individual neurons have the potential to contribute axons to both ascending pathways. A double-fluorescent tracer strategy was used in rats (red Retrobeads and Fluoro-Ruby or green Retrobeads and Fluoro-Emerald) to map the spatial distribution of cells of origin of the two projections in the lumbar spinal cord. The two pathways were found to receive input from almost entirely separate territories within the lumbar cord (levels L3–L5). GN predominantly receives input from lamina IV, while rDAO receives its input from three cell populations: medial laminae V–VI, lateral lamina V, and medial laminae VII–VIII. Cells that had axons that branched to supply both GN and rDAO represented only about 1% of either single-labeled cell population. Overall, the findings therefore suggest functional independence of the two ascending pathways. J. Comp. Neurol. 522:2179–2190, 2014. © 2013 Wiley Periodicals, Inc.

Neural circuits in movement control

Neural circuits in movement control

Structural basis of cerebellar microcircuits in the rat.

The topography of the cerebellar cortex is described by at least three different maps, with the basic units of each map termed "microzones," "patches," and "bands." These are defined, respectively, by different patterns of climbing fiber input, mossy fiber input, and Purkinje cell (PC) phenotype. Based on embryological development, the "one-map" hypothesis proposes that the basic units of each map align in the adult animal and the aim of the present study was to test this possibility. In barbiturate anesthetized adult rats, nanoinjections of bidirectional tracer (Retrobeads and biotinylated dextran amine) were made into somatotopically identified regions within the hindlimb C1 zone in copula pyramidis. Injection sites were mapped relative to PC bands defined by the molecular marker zebrin II and were correlated with the pattern of retrograde cell labeling within the inferior olive and in the basilar pontine nuclei to determine connectivity of microzones and patches, respectively, and also with the distributions of biotinylated dextran amine-labeled PC terminals in the cerebellar nuclei. Zebrin bands were found to be related to both climbing fiber and mossy fiber inputs and also to cortical representation of different parts of the ipsilateral hindpaw, indicating a precise spatial organization within cerebellar microcircuitry. This precise connectivity extends to PC terminal fields in the cerebellar nuclei and olivonuclear projections. These findings strongly support the one-map hypothesis and suggest that, at the microcircuit level of resolution, the cerebellar cortex has a common plan of spatial organization for major inputs, outputs, and PC phenotype.

Organization of cerebral projections to identified cerebellar zones in the posterior cerebellum of the rat.

The cerebrocerebellar connection makes use of two of the largest fiber tracts in the mammalian brain, i.e., the cerebral and medial cerebellar peduncles. Neuroanatomical approaches aimed to elucidate the organization of this important connection have been hindered by its multisynaptic nature, the complex organization of its components, and the dependency of conventional tracers on precisely placed injections. To overcome these problems, we used rabies virus (RV) as a retrograde transneuronal tracer. RV was injected simultaneously with cholera toxin β subunit (CTb) into selected areas of the cerebellar cortex of 18 male Wistar rats. A survival time of 48-50 h resulted in first- and second-order labeling of RV in combination with first-order labeling of CTb. The distribution of CTb-labeled neurons in the inferior olive established the zonal identity of the injection site. In this way, it was possible to examine the cortical distribution of neurons from which disynaptic cerebrocerebellar projections to specific cerebellar loci originate. The results show that this distribution covaries with the identity of the injected cerebellar lobule. More subtle changes were present when different zones of the same lobule were injected. The C1 zone of lobule VIII receives a more prominent projection from the somatosensory cortex compared with the C2/D zones. The laterally positioned D zones receive information from more rostral regions of the cerebral cortex. The vermis of lobule VII receives a prominent input from the retrosplenial and orbitofrontal cortices. Different injection sites also result in differences in laterality of the connections.

Spatial localization and projection densities of brainstem mossy fibre afferents to the forelimb C1 zone of the rat cerebellum.

The present study uses a double retrograde tracer technique in rats to examine the spatial localization and pattern of axonal branching in mossy fibres arising from three major sources in the medulla-the external cuneate nucleus, the sensory trigeminal nucleus and the reticular formation, to two electrophysiologically-identified parts of the cerebellar cortex that are linked by common climbing fibre input - the forelimb-receiving parts of the C1 zone in lobulus simplex and the paramedian lobule. In each experiment a small injection of rhodamine-tagged beads was injected into one cortical region and an injection of fluorescein-tagged beads was injected into the other region. The main findings were: (i) the proportion of double-labelled cells in each of the three precerebeller sources of mossy fibres was positively correlated with those in the inferior olive; and (ii) the C1 zone in lobulus simplex was found to receive a greater density of projections from all three sources of mossy fibres than the C1 zone in the paramedian lobule. These data suggest that two rostrocaudally separated but somatotopically corresponding parts of the C1 zone receive common mossy fibre and climbing fibre inputs. However, the differences in projection densities also suggest that the two parts of the zone differ in the extent to which they receive mossy fibre signals arising from the same precerebellar nuclei. This implies differences in function between somatotopically corresponding parts of the same cortical zone, and could enable a higher degree of parallel processing and integration of information within them.

Receptive field remodeling induced by skin stimulation in cerebellar neurons in vivo

The receptive field of a neuron reflects its function. For example, for parallel fiber (PF) inputs in C3 zone the cerebellar cortex, the excitatory and inhibitory receptive fields of a Purkinje cell (PC) have different locations, and each location has a specific relationship to the location of the climbing fiber (CF) receptive field of the PC. Previous studies have shown that this pattern of input connectivity to the PC and its afferent inhibitory interneurons can be fundamentally disrupted by applying direct electrical stimulation to the PFs, paired or unpaired with CF activation, with protocols that induce plasticity in these synapses. However, afferent fiber stimulation, which is typically used in experimental studies of plasticity, set up highly artificial input patterns at the level of the recipient cells, raising the issue that these forms of plasticity potentially may not occur under more natural input patterns. Here we used skin stimulation to set up spatiotemporally more realistic afferent input patterns in the PFs to investigate whether these input patterns are also capable of inducing synaptic plasticity using similar protocols that have previously been described for direct PF stimulation. We find that receptive field components can be added to and removed from PCs and interneurons following brief periods of skin stimulation. Following these protocols, the receptive fields of mossy fibers were unchanged. These findings confirm that previously described plasticity protocols may have a functional role also for more normal patterns of afferent input.

Mechanisms of synchronous activity in cerebellar Purkinje cells

Complex spike synchrony is thought to be a key feature of how inferior olive climbing fibre afferents make their vital contribution to cerebellar function. However, little is known about whether the other major cerebellar input, the mossy fibres (which generate simple spikes within Purkinje cells, PCs), exhibit a similar synchrony in impulse timing. We have used a multi-microelectrode system to record simultaneously from two or more PCs in the posterior lobe of the ketamine/xylazine-anaesthetized rat to examine the relationship between complex spike and simple spike synchrony in PC pairs located mainly in the A2 and C1 zones in crus II and the paramedian lobule. PC pairs displaying correlations in the occurrence of their complex spikes (coupled PCs) were usually located in the same zone and were also more likely to exhibit correlations in the timing of their spontaneous simple spikes and associated pauses in activity. In coupled PCs, synchrony in both complex spike and simple spike activity was enhanced and the relative timing in the occurrence of complex spikes could be altered by peripheral stimulation. We conclude that the functional coupling between PC pairs in their complex spike and simple spike activity can be significantly modified by sensory inputs, and that mechanisms besides electrotonic coupling are involved in generating PC synchrony. Synchronous activity in multiple PCs converging onto the same cerebellar nuclear cells is likely to have a significant impact on cerebellar output that could form important timing signals to orchestrate coordinated movements.

Analysis of formation pressure test results in the Mount Elbert methane hydrate reservoir through numerical simulation

Targeting the methane hydrate (MH) bearing units C and D at the Mount Elbert prospect on the Alaska North Slope, four MDT (Modular Dynamic Formation Tester) tests were conducted in February 2007. The C2 MDT test was selected for history matching simulation in the MH Simulator Code Comparison Study. Through history matching simulation, the physical and chemical properties of the unit C were adjusted, which suggested the most likely reservoir properties of this unit. Based on these properties thus tuned, the numerical models replicating “Mount Elbert C2 zone like reservoir”, “PBU L-Pad like reservoir” and “PBU L-Pad down dip like reservoir” were constructed. The long term production performances of wells in these reservoirs were then forecasted assuming the MH dissociation and production by the methods of depressurization, combination of depressurization and wellbore heating, and hot water huff and puff. The predicted cumulative gas production ranges from 2.16 × 10 6 m 3/well to 8.22 × 10 8 m 3/well depending mainly on the initial temperature of the reservoir and on the production method. This paper describes the details of modeling and history matching simulation. This paper also presents the results of the examinations on the effects of reservoir properties on MH dissociation and production performances under the application of the depressurization and thermal methods.

Extending the bandwidth of long‐term plasticity at the cerebellar input stage

Extending the bandwidth of long‐term plasticity at the cerebellar input stage

The periaqueductal grey modulates sensory input to the cerebellum: a role in coping behaviour?

The paths that link the periaqueductal grey (PAG) to hindbrain motor circuits underlying changes in behavioural responsiveness to external stimuli are unknown. A major candidate structure for mediating these effects is the cerebellum. The present experiments test this directly by monitoring changes in size of cerebellar responses evoked by peripheral stimuli following activation of the PAG. In 22 anaesthetized adult Wistar rats, climbing fibre field potentials were recorded from the C1 zone in the paramedian lobule and the copula pyramidis of the cerebellar cortex evoked, respectively, by electrical stimulation of the ipsilateral fore- and hindlimb. An initial and a late response were attributable to activation of Abeta and Adelta peripheral afferents respectively (hindlimb onset latencies 16.9 and 23.8 ms). Chemical stimulation at physiologically-identified sites in the ventrolateral PAG (a region known to be associated with hyporeactive immobility) resulted in a significant reduction in size of both the Abeta and Adelta evoked field potentials (mean reduction relative to control +/- SEM, 59 +/- 7.5 and 66 +/- 11.9% respectively). Responses evoked by electrical stimulation of the dorsal or ventral funiculus of the spinal cord were also reduced by PAG stimulation, suggesting that part of the modulation may occur at supraspinal sites (including at the level of the inferior olive). Overall, the results provide novel evidence of descending control into motor control centres, and provide the basis for future studies into the role of the PAG in regulating motor activity in different behavioural states and in chronic pain.

Serum levels of polychlorinated dibenzodioxins and dibenzofurans and PCBs in the general population living near an urban waste treatment plant in Biscay, Basque Country

Levels of PCDD/Fs and dioxin-like PCBs were measured in 16 pooled samples of serum from a total of 322 adults in the general population, to coincide with the start-up of a new municipal solid urban waste treatment plant in Biscay, Basque Country (Spain). Two hundred and eighty-three individual serum samples were also obtained, in which the most common PCBs (28, 52, 101, 118, 138, 153 and 180) were quantified. The samples were taken from four geographical zones: two from the metropolitan area of Bilbao, located less than 2 km from the plant and with high traffic density (Zones E1 and E2), a third located 5 km from the plant in an urban area of Bilbao, also with high traffic density (Zone C1) and the fourth located 20 km from the plant, in a municipality with minimal industrial activity and low traffic density (Zone C2), the latter two being out of the path of the prevailing winds. The median levels of dioxins+furans were similar by zone: E1 = 24.3, E2 = 27.3, C1 = 21.3, C2 = 18.8 pg g −1 lipid (p = 0.362); by sex: 20.2 vs. 22.6 pg g −1 lipid in men and women (p = 0.328); and by age: 20.8 vs. 21.3 pg g −1 lipid in subjects aged 20–44 and 45–69 ( p = 0.505). No detectable levels of PCBs 52 and 101 were found. Significant differences by zone were found only for PCB 180 ( p = 0.041), with higher values in Zone C2, the zone with the lowest presumed contamination levels. Dioxin-like PCBs ( p < 0.001) and the most common PCBs (138, 153, 180) ( p < 0.001) were both statistically associated with age, higher values being found in the 45–69 age group.

Synaptic Integration in Cerebellar Granule Cells

To understand the function of cerebellar granule cells, we need detailed knowledge about the information carried by their afferent mossy fibers and how this information is integrated by the granule cells. Recently, we made whole cell recordings from granule cells in the non-anesthetized, decerebrate cats. All recordings were made in the forelimb area of the C3 zone for which the afferent and efferent connections and functional organization have been investigated in detail. Major findings of the study were that the mossy fiber input to single granule cells was modality- and receptive field-specific and that simultaneous activity in two and usually more of the afferent mossy fibers were required to activate the granule cell spike. The high threshold for action potentials and the convergence of afferents with virtually identical information suggest that an important function of granule cells is to increase the signal-to-noise ratio of the mossy fiber-parallel fiber information. Thus a high-sensitivity, noisy mossy fiber input is transformed by the granule cell to a high-sensitivity, low-noise signal.

Properties of Somatosensory Synaptic Integration in Cerebellar Granule CellsIn Vivo

In decerebrated, nonanesthetized cats, we made intracellular whole-cell recordings and extracellular cell-attached recordings from granule cells in the cerebellar C3 zone. Spontaneous EPSPs had large, relatively constant peak amplitudes, whereas IPSPs were small and did not appear to contribute substantially to synaptic integration at a short time scale. In many cases, the EPSPs of individual mossy fiber synapses appeared to be separable by their peak amplitudes. A substantial proportion of our granule cells had small receptive fields on the forelimb skin. Skin stimulation evoked explosive responses in which the constituent EPSPs were analyzed. In the rising phase of the response, our analyses indicated a participation of three to four different mossy fiber synapses, corresponding to the total number of mossy fiber afferents. The cutaneous receptive fields of the driven EPSPs overlapped, indicating an absence of convergence of mossy fibers activated from different receptive fields. Also in granule cells activated by joint movements did we find indications that different afferents were driven by the same type of input. Regardless of input type, the temporal patterns of granule cell spike activity, both spontaneous and evoked, appeared to primarily follow the activity in the presynaptic mossy fibers, although much of the nonsynchronized mossy fiber input was filtered out. In contrast to the prevailing theories of granule cell function, our results suggest a function of granule cells as signal-to-noise enhancing threshold elements, rather than as sparse coding pattern discriminators or temporal pattern generators.

A novel site of synaptic relay for climbing fibre pathways relaying signals from the motor cortex to the cerebellar cortical C1 zone

The climbing fibre projection from the motor cortex to the cerebellar cortical C1 zone in the posterior lobe of the rat cerebellum was investigated using a combination of physiological, anatomical and neuropharmacological techniques. Electrical stimulation of the ipsilateral fore- or hindimbs or somatotopically corresponding parts of the contralateral motor cortex evoked climbing fibre field potentials at the same cerebellar recording sites. Forelimb-related responses were located in the C1 zone in the paramedian lobule or lobulus simplex and hindlimb-related responses were located in the C1 zone in the copula pyramidis. Microinjections of anterograde axonal tracer (Fluoro-Ruby or Fluoro-Emerald) were made into the fore- or hindlimb parts of the motor cortex where stimulation evoked the largest cerebellar responses. After a survival period of 7-10 days, the neuraxis was examined for anterograde labelling. No terminal labelling was ever found in the inferior olive, but labelled terminals were consistently found in a well-localized site in the dorso-medial medulla, ventral to the gracile nucleus, termed the matrix region. Pharmacological inactivation of the matrix region (2 mm caudal to the obex) selectively reduced transmission in descending (cerebro-olivocerebellar) but not ascending (spino-olivocerebellar) paths targeting fore- or hindlimb-receiving parts of the C1 zone. Transmission in spino-olivocerebellar paths was either unaffected, or in some cases increased. The identification of a novel pre-olivary relay in cerebro-olivocerebellar paths originating from fore- and hindlimb motor cortex has implications for the regulation of transmission in climbing fibre pathways during voluntary movements and motor learning.