Purkinje cell complex spike activity during voluntary motor learning: relationship to kinematics

1994 ◽  
Vol 72 (6) ◽  
pp. 2617-2630 ◽  
Author(s):  
C. L. Ojakangas ◽  
T. J. Ebner
Keyword(s):  
Motor Learning ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
The Novel ◽  
Learning Paradigm ◽  
Complex Spike ◽  
Control Phase ◽  
Voluntary Motor ◽  
Testing Phase ◽  
The Relationship

1. We examined the relationship of cerebellar Purkinje cell discharge to the scaling of kinematics during a voluntary motor learning paradigm. The study focused on whether the occurrence of complex spike (CS) discharge was associated with kinematic changes. Two primates (Macaca mulatta) were trained to move a cursor using a two-joint manipulandum over a horizontal video screen from a start target to one of four target boxes. The relationship between the cursor and the hand (gain) was changed, requiring scaling of movement distance to complete the task. As previously described, when the novel gain was presented over 100-200 movement trials the animals adapted their movements by using a strategy of scaling the amplitude and velocity of the first phase of the movement while keeping time to peak velocity constant. 2. The paradigm consisted of four different phases. A control phase at a gain of 1.0 was initially performed. The learning phase over the next 180-210 movements used one of four gains (0.6, 0.75, 1.5, or 2.0). Last, a testing phase involved 80% of 100 trials at the learned gain and 20% of the trials at the control gain of 1.0. The distance control phase consisted of using a gain of 1.0 but having the animal move to targets placed at the distance and direction the hand moved in the adapted state. 3. Simple spikes (SSs) and CSs of 141 Purkinje cells recorded primarily in the intermediate and lateral regions of zones V and VI in three cerebellar hemispheres from the two primates were recorded during the distance control, control, learning, and testing phases. Some cells were recorded in lobule VII and Crus I. CS activity increased during the learning phase, as documented previously. The increase in CS discharge occurred before or during the first 200-300 ms of the movement. This is the same time period in which the kinematic changes necessary for adaptation to the novel gain occur. Of 141 Purkinje cells recorded during the learning paradigm, 104 (74%) demonstrated significant increases in CS firing rate during the learning-testing phase. Of these 104 cells, 82 had statistically significant SS modulation. 4. Movement trials with CSs were separated from the trials without CSs. Aligning the kinematic and spike train data on movement onset, the average velocity profiles were subtracted from each other and a strict statistical criterion applied to test for the significance of any differences. Movement trials randomly sorted into two groups served as a control.(ABSTRACT TRUNCATED AT 400 WORDS)

Developmental Changes in Evoked Purkinje Cell Complex Spike Responses

2003 ◽  
Vol 90 (4) ◽  
pp. 2349-2357 ◽  
Author(s):  
Daniel A. Nicholson ◽  
John H. Freeman
Keyword(s):  
Motor Learning ◽  
Purkinje Cell ◽  
Inferior Olive ◽  
Cell Complex ◽  
Climbing Fibers ◽  
Somatosensory Stimulation ◽  
Complex Spike ◽  
Long Latency ◽  
Inhibitory Feedback ◽  
Complex Spikes

The development of synaptic interconnections between the cerebellum and inferior olive, the sole source of climbing fibers, could contribute to the ontogeny of certain forms of motor learning (e.g., eyeblink conditioning). Purkinje cell complex spikes are produced exclusively by climbing fibers and exhibit short- and long-latency activity in response to somatosensory stimulation. Previous studies have demonstrated that evoked short- and long-latency complex spikes generally occur on separate trials and that this response segregation is regulated by inhibitory feedback to the inferior olive. The present experiment tested the hypothesis that complex spikes evoked by periorbital stimulation are regulated by inhibitory feedback from the cerebellum and that this feedback develops between postnatal days (PND) 17 and 24. Recordings from individual Purkinje cell complex spikes in urethan-anesthetized rats indicated that the segregation of short- and long-latency evoked complex spike activity emerges between PND17 and PND24. In addition, infusion of picrotoxin, a GABAA-receptor antagonist, into the inferior olive abolished the response pattern segregation in PND24 rats, producing evoked complex spike response patterns similar to those characteristic of younger rats. These data support the view that cerebellar feedback to the inferior olive, which is exclusively inhibitory, undergoes substantial changes in the same developmental time window in which certain forms of motor learning emerge.

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.

scholarly journals Climbing Fiber Discharge Regulates Cerebellar Functions by Controlling the Intrinsic Characteristics of Purkinje Cell Output

2007 ◽  
Vol 97 (4) ◽  
pp. 2590-2604 ◽  
Author(s):  
Bruce E. McKay ◽  
Jordan D. T. Engbers ◽  
W. Hamish Mehaffey ◽  
Grant R. J. Gordon ◽  
Michael L. Molineux ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Motor Coordination ◽  
Climbing Fiber ◽  
State Transitions ◽  
Cellular Functions ◽  
Complex Spike ◽  
Network Activation ◽  
Cellular Factors

The contribution of Purkinje cells to cerebellar motor coordination and learning is determined in part by the chronic and acute effects of climbing fiber (CF) afferents. Whereas the chronic effects of CF discharge, such as the depression of conjunctive parallel fiber (PF) inputs, are well established, the acute cellular functions of CF discharge remain incompletely understood. In rat cerebellar slices, we show that CF discharge presented at physiological frequencies substantially modifies the frequency and pattern of Purkinje cell spike output in vitro. Repetitive CF discharge converts a spontaneous trimodal pattern of output characteristic of Purkinje cells in vitro to a more naturalistic nonbursting pattern consisting of spike trains interrupted by short CF-evoked pauses or longer pauses associated with state transitions. All effects of CF discharge could be reproduced in the presence of synaptic blockers by using current injections to simulate complex spike depolarizations, revealing that CF-evoked changes in Purkinje cell output can occur independently of network activation. Rather postsynaptic changes are sufficient to account for the CF-evoked block of trimodal activity and include at least the activation of Ca2+-dependent K+ channels. Furthermore by controlling the frequency of Purkinje cell spike output over three discrete firing levels, CF discharge modulates the gain of Purkinje cell responsiveness to PF inputs in vitro through postsynaptic mechanisms triggered by the complex spike depolarization. The ability for CF discharge to acutely modulate diverse aspects of Purkinje cell output provides important insights into the probable cellular factors contributing to motor disturbances following CF denervation.

scholarly journals Purkinje-cell plasticity and cerebellar motor learning are graded by complex-spike duration

Nature ◽  
2014 ◽  
Vol 510 (7506) ◽  
pp. 529-532 ◽  
Author(s):  
Yan Yang ◽  
Stephen G. Lisberger
Keyword(s):  
Motor Learning ◽  
Purkinje Cell ◽  
Cell Plasticity ◽  
Complex Spike

scholarly journals In vivo analysis of Purkinje cell firing properties during postnatal mouse development

2015 ◽  
Vol 113 (2) ◽  
pp. 578-591 ◽  
Author(s):  
Marife Arancillo ◽  
Joshua J. White ◽  
Tao Lin ◽  
Trace L. Stay ◽  
Roy V. Sillitoe
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Motor Behavior ◽  
Developmental Trajectories ◽  
Cell Activity ◽  
Mouse Development ◽  
Complex Spike ◽  
Simple Spike ◽  
Spike Firing

Purkinje cell activity is essential for controlling motor behavior. During motor behavior Purkinje cells fire two types of action potentials: simple spikes that are generated intrinsically and complex spikes that are induced by climbing fiber inputs. Although the functions of these spikes are becoming clear, how they are established is still poorly understood. Here, we used in vivo electrophysiology approaches conducted in anesthetized and awake mice to record Purkinje cell activity starting from the second postnatal week of development through to adulthood. We found that the rate of complex spike firing increases sharply at 3 wk of age whereas the rate of simple spike firing gradually increases until 4 wk of age. We also found that compared with adult, the pattern of simple spike firing during development is more irregular as the cells tend to fire in bursts that are interrupted by long pauses. The regularity in simple spike firing only reached maturity at 4 wk of age. In contrast, the adult complex spike pattern was already evident by the second week of life, remaining consistent across all ages. Analyses of Purkinje cells in alert behaving mice suggested that the adult patterns are attained more than a week after the completion of key morphogenetic processes such as migration, lamination, and foliation. Purkinje cell activity is therefore dynamically sculpted throughout postnatal development, traversing several critical events that are required for circuit formation. Overall, we show that simple spike and complex spike firing develop with unique developmental trajectories.

Increase in Purkinje cell gain associated with naturally activated climbing fiber input

1983 ◽  
Vol 50 (1) ◽  
pp. 205-219 ◽  
Author(s):  
T. J. Ebner ◽  
Q. X. Yu ◽  
J. R. Bloedel
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Mossy Fiber ◽  
Climbing Fiber ◽  
Peripheral Stimulus ◽  
Short Term ◽  
Spike Response ◽  
Complex Spike ◽  
Simple Spike ◽  
Complex Spikes

These experiments were designed to test the hypothesis that climbing fiber inputs evoked by a peripheral stimulus increase the responsiveness of Purkinje cells to mossy fiber inputs. This hypothesis was based on a previous series of observations demonstrating that spontaneous climbing fiber inputs are associated with an accentuation of the Purkinje cell responses to subsequent mossy fiber inputs (10, 12). Furthermore, short-term nonpersistent interactions between climbing and mossy fiber inputs have been an important aspect of many theories of cerebellar function (5, 7, 8, 12, 36). Extracellular unitary recordings were made from Purkinje cells in lobule V of decerebrate, unanesthetized cats. To activate mossy and climbing fiber inputs, the forepaw was passively flexed by a Ling vibrator system. A data analysis was developed to sort the simple spike trials into two groups, based on the presence or absence of complex spikes activated by the stimulus. In addition, during those trials in which complex spikes were activated, the simple spike train was aligned on the occurrence of the complex spike. For each simple spike response to the forepaw input, the average firing rate during the response was compared to background both in those trials in which complex spikes were activated and in those in which they were not. The ratio of the response amplitudes in the histograms constructed from these two groups of trials permitted a quantification of the change in responsiveness when climbing fiber inputs were activated. The results show that both excitatory and inhibitory simple spike responses are accentuated when associated with the activation of a complex spike. Using an arbitrary level of a gain change ratio of 120% as indicating a significant modification, 64% of the response components analyzed increased their amplitude when climbing fiber input was present. Simple spike response components occurring prior to complex spike activation were usually not accentuated, although in a few cells the amplitude of this component of the response increased. In addition, in a small number of cells the occurrence of complex spikes was associated with a new simple spike component. For excitatory responses, the magnitude of the gain change ratio was shown to be inversely related to the amplitude of the simple spike response evoked by the mossy fiber inputs. The data obtained is consistent with the hypothesis that the climbing fiber input is associated with an increase in the responsiveness of Purkinje cells to mossy fiber inputs. The increased responsiveness occurs whether the simple spike modulation evoked by the peripheral stimulus is excitatory or inhibitory. The change in responsiveness is short term and nonpersistent. It is argued that the activation of climbing fiber inputs to the cerebellar cortex is associated with an increase in the gain of Purkinje cells to mossy fiber inputs activated by natural peripheral stimuli.

scholarly journals Ethanol effects on the olivocerebellar system

1982 ◽  
Vol 60 (5) ◽  
pp. 610-614 ◽  
Author(s):  
J. G. Sinclair ◽  
G. F. Lo ◽  
D. P. Harris
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Inferior Olive ◽  
Climbing Fibre ◽  
Complex Spike ◽  
Anaesthetized Rats ◽  
Cerebellar Purkinje Cells ◽  
Cell Synapse

Ethanol (1.5 g/kg i.v.) was found to decrease spontaneous complex spike (CS) activity in cerebellar Purkinje cells in urethane anaesthetized rats while not changing the threshold required to evoke a CS by juxtafastigial stimulation. Thus ethanol does not decrease CS activity by an action at the climbing fibre – Purkinje cell synapse. Tremor induced by harmaline (5 mg/kg i.v.) in unanaesthetized animals was markedly antagonized by ethanol (0.5–2.0 g/kg i.v.) in all animals tested. However, in nine urethane-anaesthetized animals, ethanol markedly reversed the effects of harmaline on Purkinje cells in only two cases and partially reversed the effects in another four cells. Thus, the depressant effects of ethanol on the inferior olive is not totally responsible for the blockade of the harmaline tremor but would account for the decrease in spontaneous CS activity.

scholarly journals Association Between Dendritic Lamellar Bodies and Complex Spike Synchrony in the Olivocerebellar System

1997 ◽  
Vol 77 (4) ◽  
pp. 1747-1758 ◽  
Author(s):  
C. I. De Zeeuw ◽  
S.K.E. Koekkoek ◽  
D.R.W. Wylie ◽  
J. I. Simpson
Keyword(s):  
Purkinje Cell ◽  
Gap Junctions ◽  
Purkinje Cells ◽  
Inferior Olive ◽  
Cerebellar Nuclei ◽  
Climbing Fibers ◽  
Lamellar Bodies ◽  
Spike Synchrony ◽  
Complex Spike ◽  
Simple Spike

De Zeeuw, C. I., S.K.E. Koekkoek, D.R.W. Wylie, and J. I. Simpson. Association between dendritic lamellar bodies and complex spike synchrony in the olivocerebellar system. J. Neurophysiol. 77: 1747–1758, 1997. Dendritic lamellar bodies have been reported to be associated with dendrodendritic gap junctions. In the present study we investigated this association at both the morphological and electrophysiological level in the olivocerebellar system. Because cerebellar GABAergic terminals are apposed to olivary dendrites coupled by gap junctions, and because lesions of cerebellar nuclei influence the coupling between neurons in the inferior olive, we postulated that if lamellar bodies and gap junctions are related, then the densities of both structures will change together when the cerebellar input is removed. Lesions of the cerebellar nuclei in rats and rabbits resulted in a reduction of the density of lamellar bodies, the number of lamellae per lamellar body, and the density of gap junctions in the inferior olive, whereas the number of olivary neurons was not significantly reduced. The association between lamellar bodies and electrotonic coupling was evaluated electrophysiologically in alert rabbits by comparing the occurrence of complex spike synchrony in different Purkinje cell zones of the flocculus that receive their climbing fibers from olivary subnuclei with different densities of lamellar bodies. The complex spike synchrony of Purkinje cell pairs, that receive their climbing fibers from an olivary subnucleus with a high density of lamellar bodies, was significantly higher than that of Purkinje cells, that receive their climbing fibers from a subnucleus with a low density of lamellar bodies. To investigate whether the complex spike synchrony is related to a possible synchrony between simple spikes, we recorded simultaneously the complex spike and simple spike responses of Purkinje cell pairs during natural visual stimulation. Synchronous simple spike responses did occur, and this synchrony tended to increase as the synchrony between the complex spikes increased. This relation raises the possibility that synchronously activated climbing fibers evoke their effects in part via the simple spike response of Purkinje cells. The present results indicate that dendritic lamellar bodies and dendrodendritic gap junctions can be downregulated concomitantly, and that the density of lamellar bodies in different olivary subdivisions is correlated with the degree of synchrony of their climbing fiber activity. Therefore these data support the hypothesis that dendritic lamellar bodies can be associated with dendrodendritic gap junctions. Considering that the density of dedritic lamellar bodies in the inferior olive is higher than in any other area of the brain, this conclusion implies that electrotonic coupling is important for the function of the olivocerebellar system.

An active membrane model of the cerebellar Purkinje cell II. Simulation of synaptic responses

1994 ◽  
Vol 71 (1) ◽  
pp. 401-419 ◽  
Author(s):  
E. De Schutter ◽  
J. M. Bower
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Average Frequency ◽  
Climbing Fiber ◽  
Cerebellar Purkinje Cell ◽  
Inhibitory Synapses ◽  
Complex Spike ◽  
Simple Spike ◽  
Spike Firing

1. Both excitatory and inhibitory postsynaptic channels were added to a previously described complex compartmental model of a cerebellar Purkinje cell to examine model responses to synaptic inputs. All model parameters remained as described previously, leaving maximum synaptic conductance as the only parameter that was tuned in the studies described in this paper. Under these conditions the model was capable of reproducing physiological recorded responses to each of the major types of synaptic input. 2. When excitatory synapses were activated on the smooth dendrites of the model, the model generated a complex dendritic Ca2+ spike similar to that generated by climbing fiber inputs. Examination of the model showed that activation of P-type Ca2+ channels in both the smooth and spiny dendrites augmented the depolarization during the complex spike and that Ca(2+)-activated K+ channels in the same dendritic regions determined the duration of the spike. When these synapses were activated under simulated current-clamp conditions the model also generated the characteristic dual reversal potential of the complex spike. The shape of the dendritic complex spike could be altered by changing the maximum conductance of the climbing fiber synapse and thus the amount of Ca2+ entering the cell. 3. To explore the background simple spike firing properties of Purkinje cells in vivo we added excitatory “parallel fiber” synapses to the spiny dendritic branches of the model. Continuous asynchronous activation of these granule cell synapses resulted in the generation of spontaneous sodium spikes. However, very low asynchronous input frequencies produced a highly regular, very fast rhythm (80–120 Hz), whereas slightly higher input frequencies resulted in Purkinje cell bursting. Both types of activity are uncharacteristic of in vivo Purkinje cell recordings. 4. Inhibitory synapses of the sort presumably generated by stellate cells were also added to the dendritic tree. When asynchronous activation of these inhibitory synapses was combined with continuous asynchronous excitatory input the model generated somatic action potentials in a much more stochastic pattern typical of real Purkinje cells. Under these conditions simulated inter-spike interval distributions resembled those found in experimental recordings. Also, as with in vivo recordings, the model did not generate dendritic bursts. This was mainly due to inhibition that suppressed the generation of dendritic Ca2+ spikes. 5. In the presence of asynchronous inhibition, changes in the average frequency of excitatory inputs modulated background simple spike firing frequencies in the natural range of Purkinje cell firing frequencies (30–100 Hz). This modulation was very sensitive to small changes in the average frequency of excitatory inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Molecular layer interneurons shape the spike activity of cerebellar Purkinje cells

2018 ◽  
Author(s):  
Amanda M. Brown ◽  
Marife Arancillo ◽  
Tao Lin ◽  
Daniel R. Catt ◽  
Joy Zhou ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Stellate Cell ◽  
Molecular Layer ◽  
Complex Spike ◽  
Gabaergic Neurotransmission ◽  
Simple Spike ◽  
Firing Properties ◽  
Spike Firing

One-sentence summaryCerebellar stellate cells and basket cells shape distinct Purkinje cell firing propertiesAbstractPurkinje cells receive synaptic input from several classes of interneurons. Here, we address the roles of inhibitory molecular layer interneurons in establishing Purkinje cell function in vivo. Using conditional genetics approaches in mice, we compare how the lack of stellate cell versus basket cell GABAergic neurotransmission sculpts the firing properties of Purkinje cells. We take advantage of an inducible Ascl1CreER allele to spatially and temporally target the deletion of the vesicular GABA transporter, Vgat, in developing neurons. Selective depletion of basket cell GABAergic neurotransmission increases the frequency of Purkinje cell simple spike firing and decreases the frequency of complex spike firing in adult behaving mice. In contrast, lack of stellate cell communication increases the regularity of Purkinje cell simple spike firing while increasing the frequency of complex spike firing. Our data uncover complementary roles for molecular layer interneurons in shaping the rate and pattern of Purkinje cell activity in vivo.

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