scholarly journals The Theories of Gerbrandus Jelgersma (1859–1942) on the Function of the Cerebellum

2021 ◽  
Author(s):  
Jan Voogd
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Mossy Fiber ◽  
Parallel Fiber ◽  
Climbing Fibers ◽  
Late Nineteenth Century ◽  
Superior Cerebellar Peduncle ◽  
Fiber System ◽  
Coordination System ◽  
Cerebellar Peduncle

AbstractGerbrandus Jelgersma published extensively on the (pathological) anatomy of the cerebellum between 1886 and 1934. Based on his observations on the double innervation of the Purkinje cells, he formulated a hypothesis on the function of the cerebellum. Both afferent systems of the cerebellum, the mossy fiber-parallel fiber system and the climbing fibers terminate on the Purkinje cell dendrites. According to Jelgersma, the mossy fiber-parallel fiber system is derived from the pontine nuclei and the inferior olive, and would transmit the movement images derived from the cerebral cortex. Spinocerebellar climbing fibers would transmit information about the execution of the movement. When the Purkinje cell compares these inputs and notices a difference between instruction and execution, it sends a correction through the descending limb of the superior cerebellar peduncle to the anterior horn cells. Jelgersma postulates that this cerebro-cerebellar coordination system shares plasticity with other nervous connections because nerve cell dendritic protrusions possess what he called amoeboid mobility: dendritic protrusions can be extended or retracted and are so able to create new connections or to abolish them. Jelgersma’s theories are discussed against the background of more recent theories of cerebellar function that, similarly, are based on the double innervation of the Purkinje cells. The amoeboid hypothesis is traced to its roots in the late nineteenth century.

scholarly journals Purkinje cell intrinsic excitability increases after synaptic long term depression

2016 ◽  
Vol 116 (3) ◽  
pp. 1208-1217 ◽  
Author(s):  
Zhen Yang ◽  
Fidel Santamaria
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Input Resistance ◽  
Parallel Fiber ◽  
Intrinsic Excitability ◽  
Hcn Channel ◽  
Membrane Excitability ◽  
Fiber System ◽  
Long Term Depression

Coding in cerebellar Purkinje cells not only depends on synaptic plasticity but also on their intrinsic membrane excitability. We performed whole cell patch-clamp recordings of Purkinje cells in sagittal cerebellar slices in mice. We found that inducing long-term depression (LTD) in the parallel fiber to Purkinje cell synapses results in an increase in the gain of the firing rate response. This increase in excitability is accompanied by an increase in the input resistance and a decrease in the amplitude of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated voltage sag. Application of a HCN channel blocker prevents the increase in input resistance and excitability without blocking the expression of synaptic LTD. We conclude that the induction of parallel fiber-Purkinje cell LTD is accompanied by an increase in excitability of Purkinje cells through downregulation of the HCN-mediated h current. We suggest that HCN downregulation is linked to the biochemical pathway that sustains synaptic LTD. Given the diversity of information carried by the parallel fiber system, we suggest that changes in intrinsic excitability enhance the coding capacity of the Purkinje cell to specific input sources.

Role of metabotropic glutamate (ACPD) receptors at the parallel fiber-Purkinje cell synapse

1992 ◽  
Vol 68 (4) ◽  
pp. 1453-1462 ◽  
Author(s):  
S. R. Glaum ◽  
N. T. Slater ◽  
D. J. Rossi ◽  
R. J. Miller
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Parallel Fiber ◽  
Membrane Properties ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Fura 2 ◽  
Metabotropic Glutamate ◽  
Cell Synapse

1. The role of metabotropic glutamate receptors at the parallel fiber (PF)-Purkinje cell synapse in cerebellum was studied by examining the actions of the active stereoisomer (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [1S,3R-ACPD (25-50 microM)] on fura-2-loaded, patch-clamped rat Purkinje cells in thin slices. 2. The bath application of 1S,3R-ACPD evoked a direct post-synaptic depolarization that readily desensitized during prolonged (> 1 min) applications of the drug. This depolarizing response to 1S,3R-ACPD differed from the slow depolarization to 1S,3R-ACPD observed in cortical neurons mediated via closure of potassium channels in that it was not associated with an obvious change in membrane conductance and was not blocked by external barium. Similarly, slow inward rectifier currents were not affected during the 1S,3R-ACPD-induced depolarization. 3. The direct depolarization induced by 1S,3R-ACPD was not mediated by N-methyl-D-aspartate (NMDA) or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid kainate (AMPA)-KA excitatory amino acid (EAA) receptor subtypes, because the response was not blocked in the presence of antagonists of these receptors. 4. The EAA antagonist L-2-amino-3-phosphonopropionic acid, which blocks 1S,3R-ACPD-induced inositide synthesis in other cell types, had no effect on the depolarizing response. 5. Fura-2 measurements of somatic [Ca2+]i revealed that [Ca2+]i was not elevated during the 1S,3R-ACPD-induced depolarization unless the cell fired calcium-dependent action potentials. 6. In addition to the direct depolarization induced by 1S,3R-ACPD, the amplitude of PF-evoked excitatory postsynaptic potentials (EPSPs) was profoundly and reversibly reduced. This effect was observed in all cells regardless of whether a direct depolarization was produced by 1S,3R-ACPD. This reduction of the PF EPSP generally preceded the onset of depolarizing responses, did not desensitize during prolonged applications of 1S,3R-ACPD, and was reversible. 7. The reversible reduction of the PF EPSP by 1S,3R-ACPD was not related to a postsynaptic blocking action of the drug, because responses of Purkinje cells to AMPA, an agonist of the EAA receptor subtype mediating the EPSP, were reversibly potentiated in the presence of 1S,3R-ACPD. 8. The nitric oxide synthesis promoter sodium nitroprusside (1-3 nM) had no effect on the amplitude of PF EPSP or the membrane properties of Purkinje cells.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals The rich get richer: synaptic remodeling between climbing fibers and Purkinje cells in the developing cerebellum begins with positive feedback addition of synapses

2019 ◽  
Author(s):  
Alyssa Michelle Wilson ◽  
Richard Schalek ◽  
Adi Suissa-Peleg ◽  
Thouis Ray Jones ◽  
Seymour Knowles-Barley ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Purkinje Cell ◽  
Postnatal Development ◽  
Purkinje Cells ◽  
Positive Feedback ◽  
Climbing Fiber ◽  
Climbing Fibers ◽  
List Type ◽  
Developing Cerebellum ◽  
Serial Electron Microscopy

SUMMARYDuring postnatal development, cerebellar climbing fibers strongly innervate a subset of their original Purkinje cell targets and eliminate their connections from the rest. In the adult, each climbing fiber innervates a small number of Purkinje cells and each Purkinje cell is innervated by a single climbing fiber. To get insight about the processes responsible for this remapping, we reconstructed serial electron microscopy datasets from mice during the first postnatal week. In contrast to adult connectivity, individual neonatal climbing fibers innervate many nearby Purkinje cells, and multiple climbing fibers innervate each Purkinje cell. Between postnatal days 3 and 7, Purkinje cells retract long dendrites and grow many proximal dendritic processes. On this changing landscape, individual climbing fibers selectively add many synapses to a subset of Purkinje cell targets in a positive-feedback manner, without pruning synapses from other Purkinje cells. The active zone sizes of synapses associated with powerful versus weak inputs are indistinguishable. These results show that changes in synapse number rather than synapse size are the predominant form of early developmental plasticity. Finally, although multiple climbing fibers innervate each Purkinje cell in early postnatal development, the number of climbing fibers and Purkinje cells in a local cerebellar region nearly match. Thus, initial over-innervation of Purkinje cells by climbing fibers is economical, in that the number of axons entering a region is enough to assure that each axon ends up with a postsynaptic target, and that none branched there in vain.HIGHLIGHTSDeveloping climbing fibers establish synapses on many neighboring Purkinje cells unlike the sparse pattern of innervation in later lifeClimbing fibers add many synapses onto a few of their Purkinje targets before the pruning stage in a rich-get-richer type processThe synapse sizes of strengthened and weakened climbing fiber inputs are indistinguishable.Exuberant branching of climbing fiber axons in early postnatal life appears to be economical because the numbers of axons and Purkinje cells in a local region match, ensuring that each axon can establish a long-lasting connection thereBLURBHigh-resolution serial electron microscopy reconstructions reveal that climbing fiber-Purkinje cell synaptic refinement in the developing cerebellum begins with significant synapse addition. Climbing fibers focus their synapses onto a smaller number of Purkinje cells by selectively adding synapses onto some target cells. All axons that project to a region in development play a role in the final connectivity.

Effect of Conditioned Stimulus Parameters on Timing of Conditioned Purkinje Cell Responses

2010 ◽  
Vol 103 (3) ◽  
pp. 1329-1336 ◽  
Author(s):  
Pär Svensson ◽  
Dan-Anders Jirenhed ◽  
Fredrik Bengtsson ◽  
Germund Hesslow
Keyword(s):  
Conditioned Stimulus ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Mossy Fiber ◽  
Eyeblink Conditioning ◽  
Mossy Fibers ◽  
Inhibitory Response ◽  
Cell Responses ◽  
Cerebellar Purkinje Cells ◽  
Adaptive Timing

Pavlovian eyeblink conditioning is a useful experimental model for studying adaptive timing, an important aspect of skilled movements. The conditioned response (CR) is precisely timed to occur just before the onset of the expected unconditioned stimulus (US). The timing can be changed immediately, however, by varying parameters of the conditioned stimulus (CS). It has previously been shown that increasing the intensity of a peripheral CS or the frequency of a CS consisting of a train of stimuli to the mossy fibers shortens the latency of the CR. The adaptive timing of behavioral CRs probably reflects the timing of an underlying learned inhibitory response in cerebellar Purkinje cells. It is not known how the latency of this Purkinje cell CR is controlled. We have recorded form Purkinje cells in conditioned decerebrate ferrets while increasing the intensity of a peripheral CS or the frequency of a mossy fiber CS. We observe changes in the timing of the Purkinje cell CR that match the behavioral effects. The results are consistent with the effect of CS parameters on behavioral CR latency being caused by corresponding changes in Purkinje cell CRs. They suggest that synaptic temporal summation may be one of several mechanisms underlying adaptive timing of movements.

Serotonergic modulation of evoked responses in turtle cerebellar Purkinje cells

1996 ◽  
Vol 76 (5) ◽  
pp. 3102-3113 ◽  
Author(s):  
H. Lu ◽  
L. J. Larson-Prior
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Cell Layer ◽  
Response Amplitude ◽  
Evoked Responses ◽  
Postsynaptic Potentials ◽  
Control Value ◽  
Bath Application ◽  
Cerebellar Peduncle

1. Immunocytochemical studies of the turtle brain revealed the presence of serotonin (5-hydroxytryptamine, 5-HT) immunoreactive (5-HT-ir) processes in the granule and Purkinje cell layers, but not in the molecular layer (ML), of the cerebellar cortex. Immunoreactive axonal profiles were present throughout the granule cell layer (GCL) where they generally coursed in an anteroposterior direction and could frequently be seen to ascend toward the Purkinje cell layer (PCL). Occasional 5-HT-ir processes were observed adjacent to Purkinje cell somata. 2. The effects of exogenously applied serotonin on mossy fiber and parallel fiber evoked responses in turtle Purkinje cells were examined by use of intrasomatic and intradendritic recordings in an intact cerebellar preparation in vitro. 3. Bath application of serotonin (0.2–1.0 microM) produced a dose-dependent reduction in Purkinje cell membrane resistance, which was not correlated with changes in postsynaptic response amplitude. At 5-HT concentrations > 1.0 microM (0.01–5 mM), resistance values returned to control levels. No consistent changes in spike width or postspike afterhyperpolarization were seen in response to serotonin application, nor were endogenous pacemaker-like discharges affected. Firing rate, assessed as threshold response to depolarizing current injection (0.3–1.0 nA, 1 s duration), was increased in 51% and decreased in 40% of cells tested. 4. Single stimuli delivered to either the cerebellar peduncle or the GCL resulted in the activation of fast excitatory postsynaptic potentials (fEPSP). These responses were dose dependently reduced in amplitude by bath application of serotonin (0.2–1.0 microM). At concentrations ranging from 10 to 100 microM, the response amplitude following agonist application plateaued at approximately 70% of control value. With higher dose applications (0.5-5 mM) of serotonin, the response amplitude exhibited a steep reduction (from 65-10% of control value). 5. Brief trains of stimuli (5 stimuli, 50 Hz) delivered to either the cerebellar peduncle or the GCL resulted in the activation of slow excitatory postsynaptic potentials (sEPSP). The peak amplitude of this response was unaffected by bath application of serotonin at concentrations ranging from 0.2 to 100 microM. At higher concentrations (0.5–5 mM), the sEPSP peak amplitude was dose-dependently reduced, with the largest amplitude reduction seen after peduncular stimulation. 6. It is suggested that serotonin acts as a modulator of fast excitatory synaptic activity in the cerebellar cortex, while exerting little affect on slow excitatory events. The fact that serotonin preferentially affects fast excitatory transmission may have important implications for the integration of incoming sensory signals at both the granule and Purkinje cell level.

scholarly journals Alcohol Impairs Long-Term Depression at the Cerebellar Parallel Fiber–Purkinje Cell Synapse

2008 ◽  
Vol 100 (6) ◽  
pp. 3167-3174 ◽  
Author(s):  
Amor Belmeguenai ◽  
Paolo Botta ◽  
John T. Weber ◽  
Mario Carta ◽  
Martijn De Ruiter ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Motor Learning ◽  
Synaptic Transmission ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Motor Coordination ◽  
Parallel Fiber ◽  
Calcium Currents ◽  
Long Term Depression

Acute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor learning. It has previously been shown that ethanol modulates inhibitory transmission in the cerebellum and affects synaptic transmission and plasticity at excitatory climbing fiber (CF) to Purkinje cell synapses. However, it has not been examined thus far how acute ethanol application affects long-term depression (LTD) and long-term potentiation (LTP) at excitatory parallel fiber (PF) to Purkinje cell synapses, which are assumed to mediate forms of cerebellar motor learning. To examine ethanol effects on PF synaptic transmission and plasticity, we performed whole cell patch-clamp recordings from Purkinje cells in rat cerebellar slices. We found that ethanol (50 mM) selectively blocked PF–LTD induction, whereas it did not change the amplitude of excitatory postsynaptic currents at PF synapses. In contrast, ethanol application reduced voltage-gated calcium currents and type 1 metabotropic glutamate receptor (mGluR1)–dependent responses in Purkinje cells, both of which are involved in PF–LTD induction. The selectivity of these effects is emphasized by the observation that ethanol did not impair PF–LTP and that PF–LTP could readily be induced in the presence of the group I mGluR antagonist AIDA or the mGluR1a antagonist LY367385. Taken together, these findings identify calcium currents and mGluR1-dependent signaling pathways as potential ethanol targets and suggest that an ethanol-induced blockade of PF–LTD could contribute to the motor coordination deficits resulting from alcohol consumption.

Anatomical structure alone cannot predict function

1997 ◽  
Vol 20 (2) ◽  
pp. 252-253 ◽  
Author(s):  
Dieter Jaeger ◽  
Erik De Schutter
Keyword(s):  
Purkinje Cell ◽  
Computer Simulations ◽  
Mossy Fiber ◽  
Anatomical Structure ◽  
Parallel Fiber ◽  
Tidal Waves ◽  
Central Hypothesis ◽  
Target Article ◽  
Modeling Data ◽  
Excitatory Responses

The central hypothesis of Braitenberg et al.'s target article – that tidal waves of parallel fiber excitation precisely activate Purkinje cell spiking – is hard to reconcile with recent neurophysiological and modeling data. The assumed pattern of mossy fiber input seems unrealistic, inhibition is likely to interfere with the proposed excitatory responses, and moreover, computer simulations show that the Purkinje cell is a poor coincidence detector.

The detection and generation of sequences as a key to cerebellar function: Experiments and theory

1997 ◽  
Vol 20 (2) ◽  
pp. 229-245 ◽  
Author(s):  
Valentino Braitenberg ◽  
Detlef Heck ◽  
Fahad Sultan
Keyword(s):  
Cerebral Cortex ◽  
Purkinje Cells ◽  
Mossy Fiber ◽  
Motor Planning ◽  
Movement Control ◽  
Fiber System ◽  
Specific Sequence ◽  
Functional Interpretation ◽  
Parallel Fibers ◽  
Sequential Activation

Starting from macroscopic and microscopic facts of cerebellar histology, we propose a new functional interpretation that may elucidate the role of the cerebellum in movement control. The idea is that the cerebellum is a large collection of individual lines (Eccles's “beams”: Eccles et al. 1967a) that respond specifically to certain sequences of events in the input and in turn produce sequences of signals in the output. We believe that the sequence-in/sequence-out mode of operation is as typical for the cerebellar cortex as the transformation of sets into sets of active neurons is typical for the cerebral cortex, and that both the histological differences between the two and their reciprocal functional interactions become understandable in the light of this dichotomy. The response of Purkinje cells to sequences of stimuli in the mossy fiber system was shown experimentally by Heck on surviving slices of rat and guinea pig cerebellum. Sequential activation of a row of eleven stimulating electrodes in the granular layer, imitating a “movement” of the stimuli along the folium, produces a powerful volley in the parallel fibers that strongly excites Purkinje cells, as evidenced by intracellular recording. The volley, or “tidal wave,” has maximal amplitude when the stimulus moves toward the recording site at the speed of conduction in parallel fibers, and much smaller amplitudes for lower or higher “velocities.” The succession of stimuli has no effect when they “move” in the opposite direction. Synchronous activation of the stimulus electrodes also had hardly any effect. We believe that the sequences of mossy fiber activation that normally produce this effect in the intact cerebellum are a combination of motor planning relayed to the cerebellum by the cerebral cortex, and information about ongoing movement, reaching the cerebellum from the spinal cord. The output elicited by the specific sequence to which a “beam” is tuned may well be a succession of well timed inhibitory volleys “sculpting” the motor sequences so as to adapt them to the complicated requirements of the physics of a multijointed system.

scholarly journals Potentiation of cerebellar Purkinje cells facilitates whisker reflex adaptation through increased simple spike activity

2018 ◽  
Author(s):  
Vincenzo Romano ◽  
Licia De Propris ◽  
Laurens W.J. Bosman ◽  
Pascal Warnaar ◽  
Michiel M. ten Brinke ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Spike Activity ◽  
Cell Activity ◽  
Response Probability ◽  
Long Term Potentiation ◽  
Parallel Fiber ◽  
Spike Response ◽  
Simple Spike ◽  
Cerebellar Plasticity

SummaryCerebellar plasticity underlies motor learning. However, how the cerebellum operates to enable learned changes in motor output is largely unknown. We developed a sensory-driven adaptation protocol for reflexive whisker protraction and recorded Purkinje cell activity from crus 1 and 2 of awake mice. Before training, simple spikes of individual Purkinje cells correlated during reflexive protraction with the whisker position without lead or lag. After training, simple spikes and whisker protractions were both enhanced with the spiking activity now leading the behavioral response. Neuronal and behavior changes did not occur in two cell-specific mouse models with impaired long-term potentiation at parallel fiber to Purkinje cell synapses. Consistent with cerebellar plasticity rules, increased simple spike activity was prominent in cells with low complex spike response probability. Thus, potentiation at parallel fiber to Purkinje cell synapses may contribute to reflex adaptation and enable expression of cerebellar learning through increases in simple spike activity.Impact statementRomano et al. show that expression of cerebellar whisker learning can be mediated by increases in simple spike activity, depending on LTP induction at parallel fiber to Purkinje cell synapses.

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