scholarly journals A Purkinje cell model that simulates complex spikes

2020 ◽  
Author(s):  
Amelia Burroughs ◽  
Nadia L. Cerminara ◽  
Richard Apps ◽  
Conor Houghton

AbstractPurkinje cells are the principal neurons of the cerebellar cortex. One of their distinguishing features is that they fire two distinct types of action potential, called simple and complex spikes, which interact with one another. Simple spikes are stereotypical action potentials that are elicited at high, but variable, rates (0 – 100 Hz) and have a consistent waveform. Complex spikes are composed of an initial action potential followed by a burst of lower amplitude spikelets. Complex spikes occur at comparatively low rates (~ 1 Hz) and have a variable waveform. Although they are critical to cerebellar operation a simple model that describes the complex spike waveform is lacking. Here, a novel single-compartment model of Purkinje cell electrodynamics is presented. The simpler version of this model, with two active conductances and a leak channel, can simulate the features typical of complex spikes recorded in vitro. If calcium dynamics are also included, the model can capture the pause in simple spike activity that occurs after complex spike events. Together, these models provide an insight into the mechanisms behind complex spike spikelet generation, waveform variability and their interactions with simple spike activity.

1983 ◽  
Vol 50 (1) ◽  
pp. 205-219 ◽  
Author(s):  
T. J. Ebner ◽  
Q. X. Yu ◽  
J. R. Bloedel

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.


2019 ◽  
Author(s):  
Akshay Markanday ◽  
Joachim Bellet ◽  
Marie E. Bellet ◽  
Ziad M. Hafed ◽  
Peter Thier

AbstractOne of the most powerful excitatory synapses in the entire brain is formed by cerebellar climbing fibers, originating from neurons in the inferior olive, that wrap around the proximal dendrites of cerebellar Purkinje cells. The activation of a single olivary neuron is capable of generating a large electrical event, called “complex spike”, at the level of the postsynaptic Purkinje cell, comprising of a fast initial spike of large amplitude followed by a slow polyphasic tail of small amplitude spikelets. Several ideas discussing the role of the cerebellum in motor control are centered on these complex spike events. However, these events are extremely rare, only occurring 1-2 times per second. As a result, drawing conclusions about their functional role has been very challenging, as even few errors in their detection may change the result. Since standard spike sorting approaches cannot fully handle the polyphasic shape of complex spike waveforms, the only safe way to avoid omissions and false detections has been to rely on visual inspection of long traces of Purkinje cell recordings by experts. Here we present a supervised deep learning algorithm for rapidly and reliably detecting complex spikes as an alternative to tedious visual inspection. Our algorithm, utilizing both action potential and local field potential signals, not only detects complex spike events much faster than human experts, but it also excavates key features of complex spike morphology with a performance comparable to that of such experts.Significance statementClimbing fiber driven “complex spikes”, fired at perplexingly low rates, are known to play a crucial role in cerebellum-based motor control. Careful interpretations of these spikes require researchers to manually detect them, since conventional online or offline spike sorting algorithms (optimized for analyzing the much more frequent “simple spikes”) cannot be fully trusted. Here, we present a deep learning approach for identifying complex spikes, which is trained on local field and action potential recordings from cerebellar Purkinje cells. Our algorithm successfully identifies complex spikes, along with additional relevant neurophysiological features, with an accuracy level matching that of human experts, yet with very little time expenditure.


2017 ◽  
Vol 595 (15) ◽  
pp. 5341-5357 ◽  
Author(s):  
Tianyu Tang ◽  
Jianqiang Xiao ◽  
Colleen Y. Suh ◽  
Amelia Burroughs ◽  
Nadia L. Cerminara ◽  
...  

1999 ◽  
Vol 19 (7) ◽  
pp. 2728-2739 ◽  
Author(s):  
Eric J. Lang ◽  
Izumi Sugihara ◽  
John P. Welsh ◽  
Rodolfo Llinás

2000 ◽  
Vol 84 (6) ◽  
pp. 2945-2960 ◽  
Author(s):  
Maninder Kahlon ◽  
Stephen G. Lisberger

We followed simple- and complex-spike firing of Purkinje cells (PCs) in the floccular complex of the cerebellum through learned modifications of the pursuit eye movements of two monkeys. Learning was induced by double steps of target speed in which initially stationary targets move at a “learning” speed for 100 ms and then change to either a higher or lower speed in the same direction. In randomly interleaved control trials, targets moved at the learning speed in the opposite direction. When the learning direction was theon direction for simple-spike responses, learning was associated with statistically significant changes in simple-spike firing for 10 of 32 PCs. Of the 10 PCs that showed significant expressions of learning, 8 showed changes in simple-spike output in the expected direction: increased or decreased firing when eye acceleration increased or decreased through learning. There were no statistically significant changes in simple-spike responses or eye acceleration during pursuit in the control direction. When the learning direction was in the off direction for simple-spike responses, none of 15 PCs showed significant correlates of learning. Although changes in simple-spike firing were recorded in only a subset of PCs, analysis of the population response showed that the same relationship between population firing and eye acceleration obtained before and after learning. Thus learning is associated with changes that render the modified population response appropriate to drive the changed behavior. To analyze complex-spike firing during learning we correlated complex-spike firing in the second, third, and fourth 100 ms after the onset of target motion with the retinal image motion in the previous 100 ms. Data were largely consistent with previous evidence that image motion drives complex spikes with a direction selectivity opposite that for simple spikes. Comparison of complex-spike responses at different times after the onset of control and learning target motions in the learning direction implied that complex spikes could guide learning during decreases but not increases in eye acceleration. Learning caused increases or decreases in the sensitivity of complex spikes to image motion in parallel with changes in eye acceleration. Complex-spike responses were similar in all PCs, including many in which learning did not modify simple-spike responses. Our data do not disprove current theories of cerebellar learning but suggest that these theories would have to be modified to account for simple- and complex-spike firing of floccular Purkinje cells reported here.


1982 ◽  
Vol 237 (2) ◽  
pp. 484-491 ◽  
Author(s):  
Christopher J. McDevitt ◽  
Timothy J. Ebner ◽  
James R. Bloedel

2003 ◽  
Vol 90 (4) ◽  
pp. 2349-2357 ◽  
Author(s):  
Daniel A. Nicholson ◽  
John H. Freeman

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.


2018 ◽  
Author(s):  
Vincenzo Romano ◽  
Licia De Propris ◽  
Laurens W.J. Bosman ◽  
Pascal Warnaar ◽  
Michiel M. ten Brinke ◽  
...  

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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