52
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Fast-Reset of Pacemaking and Theta-Frequency Resonance Patterns in Cerebellar Golgi Cells: Simulations of their Impact In Vivo

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The Golgi cells are inhibitory interneurons of the cerebellar granular layer, which respond to afferent stimulation in vivo with a burst-pause sequence interrupting their irregular background low-frequency firing (Vos et al., 1999a. Eur. J. Neurosci. 11, 2621–2634). However, Golgi cells in vitro are regular pacemakers (Forti et al., 2006. J. Physiol. 574, 711–729), raising the question how their ionic mechanisms could impact on responses during physiological activity. Using patch-clamp recordings in cerebellar slices we show that the pacemaker cycle can be suddenly reset by spikes, making the cell highly sensitive to input variations. Moreover, the neuron resonates around the pacemaker frequency, making it specifically sensitive to patterned stimulation in the theta-frequency band. Computational analysis based on a model developed to reproduce Golgi cell pacemaking (Solinas et al., 2008 Front. Neurosci., 2:2) predicted that phase-reset required spike-triggered activation of SK channels and that resonance was sustained by a slow voltage-dependent potassium current and amplified by a persistent sodium current. Adding balanced synaptic noise to mimic the irregular discharge observed in vivo, we found that pacemaking converts into spontaneous irregular discharge, that phase-reset plays an important role in generating the burst-pause pattern evoked by sensory stimulation, and that repetitive stimulation at theta-frequency enhances the time-precision of spike coding in the burst. These results suggest that Golgi cell intrinsic properties exert a profound impact on time-dependent signal processing in the cerebellar granular layer.

          Related collections

          Most cited references46

          • Record: found
          • Abstract: found
          • Article: not found

          A theory of cerebellar cortex.

          D. Marr (1969)
          1. A detailed theory of cerebellar cortex is proposed whose consequence is that the cerebellum learns to perform motor skills. Two forms of input-output relation are described, both consistent with the cortical theory. One is suitable for learning movements (actions), and the other for learning to maintain posture and balance (maintenance reflexes).2. It is known that the cells of the inferior olive and the cerebellar Purkinje cells have a special one-to-one relationship induced by the climbing fibre input. For learning actions, it is assumed that:(a) each olivary cell responds to a cerebral instruction for an elemental movement. Any action has a defining representation in terms of elemental movements, and this representation has a neural expression as a sequence of firing patterns in the inferior olive; and(b) in the correct state of the nervous system, a Purkinje cell can initiate the elemental movement to which its corresponding olivary cell responds.3. Whenever an olivary cell fires, it sends an impulse (via the climbing fibre input) to its corresponding Purkinje cell. This Purkinje cell is also exposed (via the mossy fibre input) to information about the context in which its olivary cell fired; and it is shown how, during rehearsal of an action, each Purkinje cell can learn to recognize such contexts. Later, when the action has been learnt, occurrence of the context alone is enough to fire the Purkinje cell, which then causes the next elemental movement. The action thus progresses as it did during rehearsal.4. It is shown that an interpretation of cerebellar cortex as a structure which allows each Purkinje cell to learn a number of contexts is consistent both with the distributions of the various types of cell, and with their known excitatory or inhibitory natures. It is demonstrated that the mossy fibre-granule cell arrangement provides the required pattern discrimination capability.5. The following predictions are made.(a) The synapses from parallel fibres to Purkinje cells are facilitated by the conjunction of presynaptic and climbing fibre (or post-synaptic) activity.(b) No other cerebellar synapses are modifiable.(c) Golgi cells are driven by the greater of the inputs from their upper and lower dendritic fields.6. For learning maintenance reflexes, 2(a) and 2(b) are replaced by2'. Each olivary cell is stimulated by one or more receptors, all of whose activities are usually reduced by the results of stimulating the corresponding Purkinje cell.7. It is shown that if (2') is satisfied, the circuit receptor --> olivary cell --> Purkinje cell --> effector may be regarded as a stabilizing reflex circuit which is activated by learned mossy fibre inputs. This type of reflex has been called a learned conditional reflex, and it is shown how such reflexes can solve problems of maintaining posture and balance.8. 5(a), and either (2) or (2') are essential to the theory: 5(b) and 5(c) are not absolutely essential, and parts of the theory could survive the disproof of either.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Resonance, oscillation and the intrinsic frequency preferences of neurons.

            The realization that different behavioural and perceptual states of the brain are associated with different brain rhythms has sparked growing interest in the oscillatory behaviours of neurons. Recent research has uncovered a close association between electrical oscillations and resonance in neurons. Resonance is an easily measurable property that describes the ability of neurons to respond selectively to inputs at preferred frequencies. A variety of ionic mechanisms support resonance and oscillation in neurons. Understanding the basic principles involved in the production of resonance allows for a simplified classification of these mechanisms. The characterization of resonance and frequency preference captures those essential properties of neurons that can serve as a substrate for coordinating network activity around a particular frequency in the brain.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Integration of quanta in cerebellar granule cells during sensory processing.

              To understand the computations performed by the input layers of cortical structures, it is essential to determine the relationship between sensory-evoked synaptic input and the resulting pattern of output spikes. In the cerebellum, granule cells constitute the input layer, translating mossy fibre signals into parallel fibre input to Purkinje cells. Until now, their small size and dense packing have precluded recordings from individual granule cells in vivo. Here we use whole-cell patch-clamp recordings to show the relationship between mossy fibre synaptic currents evoked by somatosensory stimulation and the resulting granule cell output patterns. Granule cells exhibited a low ongoing firing rate, due in part to dampening of excitability by a tonic inhibitory conductance mediated by GABA(A) (gamma-aminobutyric acid type A) receptors. Sensory stimulation produced bursts of mossy fibre excitatory postsynaptic currents (EPSCs) that summate to trigger bursts of spikes. Notably, these spike bursts were evoked by only a few quantal EPSCs, and yet spontaneous mossy fibre inputs triggered spikes only when inhibition was reduced. Our results reveal that the input layer of the cerebellum balances exquisite sensitivity with a high signal-to-noise ratio. Granule cell bursts are optimally suited to trigger glutamate receptor activation and plasticity at parallel fibre synapses, providing a link between input representation and memory storage in the cerebellum.
                Bookmark

                Author and article information

                Journal
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Research Foundation
                1662-5102
                01 December 2007
                30 December 2007
                2007
                : 1
                : 4
                Affiliations
                [1] 1Department of Cellular and Molecular Physiological and Pharmacological Sciences, University of Pavia and CNISM Italy
                [2] 2Theoretical Neurobiology, University of Antwerp Belgium
                [3] 3Computational Neuroscience Unit, Okinawa Institute of Science and Technology Japan
                Author notes

                Edited by: Alexander Borst, Max-Planck-Institute of Neurobiology, Germany

                Reviewed by: Hermann Cuntz, University College London, UK Yosef Yarom, Hebrew University, Israel

                *Correspondence: Egidio D'Angelo, Department of Cellular and Molecular Physiological and Pharmacological Sciences, University of Pavia and CNISM, Via Forlanini 6, I-27100 Pavia, Italy. e-mail: dangelo@ 123456unipv.it
                Article
                10.3389/neuro.03.004.2007
                2525929
                18946522
                73d50101-cd0e-4485-963e-4a163d8c590a
                Copyright © 2007 Solinas, Forti, Cesana, Mapelli, De Schutter and D'Angelo.

                This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

                History
                : 26 November 2007
                : 07 December 2007
                Page count
                Figures: 7, Tables: 0, Equations: 0, References: 48, Pages: 9, Words: 6654
                Categories
                Neuroscience
                Original Research

                Neurosciences
                modeling,phase-reset,granular layer,cerebellum,resonance,golgi cell
                Neurosciences
                modeling, phase-reset, granular layer, cerebellum, resonance, golgi cell

                Comments

                Comment on this article