scholarly journals Maturation of Purkinje cell firing properties relies on neurogenesis of excitatory neurons

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Meike E van der Heijden ◽  
Elizabeth P Lackey ◽  
Ross Perez ◽  
Fatma S Ișleyen ◽  
Amanda M Brown ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Time Window ◽  
Mouse Development ◽  
Cerebellar Neurons ◽  
Cell Functions ◽  
Excitatory Neurons ◽  
Cell Firing ◽  
Firing Properties

Preterm infants that suffer cerebellar insults often develop motor disorders and cognitive difficulty. Excitatory granule cells, the most numerous neuron type in the brain, are especially vulnerable and likely instigate disease by impairing the function of their targets, the Purkinje cells. Here, we use regional genetic manipulations and in vivo electrophysiology to test whether excitatory neurons establish the firing properties of Purkinje cells during postnatal mouse development. We generated mutant mice that lack the majority of excitatory cerebellar neurons and tracked the structural and functional consequences on Purkinje cells. We reveal that Purkinje cells fail to acquire their typical morphology and connectivity, and that the concomitant transformation of Purkinje cell firing activity does not occur either. We also show that our mutant pups have impaired motor behaviors and vocal skills. These data argue that excitatory cerebellar neurons define the maturation time-window for postnatal Purkinje cell functions and refine cerebellar-dependent behaviors.

scholarly journals Maturation of Purkinje cell firing properties relies on granule cell neurogenesis

2020 ◽  
Author(s):  
Meike E. van der Heijden ◽  
Elizabeth P. Lackey ◽  
Fatma S. Işleyen ◽  
Amanda M. Brown ◽  
Ross Perez ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Granule Cell ◽  
Cell Function ◽  
Granule Cells ◽  
Time Window ◽  
Mouse Development ◽  
Cell Firing ◽  
Firing Properties

SUMMARYPreterm infants that suffer cerebellar insults often develop motor disorders and cognitive difficulty. Granule cells are especially vulnerable, and they likely instigate disease by impairing the function of Purkinje cells. Here, we use regional genetic manipulations and in vivo electrophysiology to test whether granule cells help establish the firing properties of Purkinje cells during postnatal mouse development. We generated mice that lack granule cell neurogenesis and tracked the structural and functional consequences on Purkinje cells in these agranular pups. We reveal that Purkinje cells fail to acquire their typical connectivity and morphology, and the formation of characteristic Purkinje cell firing patterns is delayed by one week. We also show that the agranular pups have impaired motor behaviors and vocal skills. These data argue that granule cell neurogenesis sets the maturation time window for Purkinje cell function and refines cerebellar-dependent behaviors.

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.

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.

scholarly journals Distribution of neurofilament subunits in neurons and neuronal processes: immunohistochemical studies of bovine cerebellum with subunit-specific monoclonal antibodies.

1985 ◽  
Vol 33 (6) ◽  
pp. 557-563 ◽  
Author(s):  
J Q Trojanowski ◽  
M A Obrocka ◽  
V M Lee
Keyword(s):  
Molecular Weight ◽  
Monoclonal Antibodies ◽  
Purkinje Cell ◽  
High Molecular Weight ◽  
Purkinje Cells ◽  
Cerebellar Neurons ◽  
Neuronal Processes ◽  
Immunohistochemical Studies

The distribution of individual neurofilament (NF) subunits in bovine cerebellar neurons was examined using monoclonal antibodies (MAs) raised against bovine NF. MAs with immunochemically defined specificities for one or more NF subunits were used. Seven were specific for the Mr 68,000 NF subunit, five were specific for the Mr 150,000 NF subunit, nine were specific for the Mr 200,000 NF subunit, and 30 recognized both high molecular weight subunits. Fresh bovine cerebellum was fixed and processed by five different protocols and subjected to four different immunohistochemical procedures. MAs from each group stained neuronal perikarya and processes. NF immunoreactivity in Purkinje cells was evaluated in detail. Adjacent Purkinje cell bodies and dendrites exhibited variable NF immunoreactivity to the same MA, ranging from intensely positive to completely negative. Similar variability in axonal staining was not observed. Application of the same MA to tissue subjected to different fixation and/or immunohistochemical protocols also resulted in variability in NF subunit immunoreactivity. We conclude that MAs recognize each of the three NF subunits in neuronal perikarya, axons, and dendrites. Variability in NF subunit immunoreactivity appears to reflect both NF microheterogeneity and fixation-dependent modifications of NF subunits.

Spatial distribution of excitatory and inhibitory synapses on a Purkinje cell in a rat cerebellar culture

1993 ◽  
Vol 70 (4) ◽  
pp. 1316-1325 ◽  
Author(s):  
T. Hirano ◽  
K. Kasono
Keyword(s):  
Spatial Distribution ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Spatial Organization ◽  
Lucifer Yellow ◽  
Inhibitory Synapses ◽  
Presynaptic Neuron ◽  
Presynaptic Terminals ◽  
Excitatory And Inhibitory Synapses

1. The spatial distribution of excitatory and inhibitory synapses on cultured Purkinje cells was studied with fluorescence, scanning electron microscopy (SEM), and electrophysiological techniques. 2. Presynaptic terminals were identified with immunohistochemical staining of synaptophysin and the results were correlated with SEM micrographs. 3. Excitatory and inhibitory inputs onto the Purkinje cell were identified from the direction and pharmacology of the postsynaptic current. 4. The localization of the presynaptic terminals on the Purkinje cell was observed after electrophysiological identification by filling the presynaptic neuron with Lucifer yellow and the Purkinje cell with Texas red. 5. The axon and presynaptic terminals of excitatory and inhibitory inputs had a different spatial organization. Excitatory inputs from granule cells were exclusively localized on the dendrites of Purkinje cells, whereas inhibitory contacts were found on both the soma and dendrites. This result is similar to that described in vivo.

scholarly journals Long-term in vivo time-lapse imaging of synapse development and plasticity in the cerebellum

2014 ◽  
Vol 111 (1) ◽  
pp. 208-216 ◽  
Author(s):  
Naoko Nishiyama ◽  
Jeremy Colonna ◽  
Elise Shen ◽  
Jennifer Carrillo ◽  
Hiroshi Nishiyama
Keyword(s):  
In Vivo Imaging ◽  
Time Window ◽  
Time Lapse ◽  
Mammalian Brain ◽  
Cerebellar Neurons ◽  
Brain Functions ◽  
Time Lapse Imaging ◽  
Synaptic Circuitry

Synapses are continuously formed and eliminated throughout life in the mammalian brain, and emerging evidence suggests that this structural plasticity underlies experience-dependent changes of brain functions such as learning and long-term memory formation. However, it is generally difficult to understand how the rewiring of synaptic circuitry observed in vivo eventually relates to changes in animal's behavior. This is because afferent/efferent connections and local synaptic circuitries are very complicated in most brain regions, hence it is largely unclear how sensorimotor information is conveyed, integrated, and processed through a brain region that is imaged. The cerebellar cortex provides a particularly useful model to challenge this problem because of its simple and well-defined synaptic circuitry. However, owing to the technical difficulty of chronic in vivo imaging in the cerebellum, it remains unclear how cerebellar neurons dynamically change their structures over a long period of time. Here, we showed that the commonly used method for neocortical in vivo imaging was not ideal for long-term imaging of cerebellar neurons, but simple optimization of the procedure significantly improved the success rate and the maximum time window of chronic imaging. The optimized method can be used in both neonatal and adult mice and allows time-lapse imaging of cerebellar neurons for more than 5 mo in ∼80% of animals. This method allows vital observation of dynamic cellular processes such as developmental refinement of synaptic circuitry as well as long-term changes of neuronal structures in adult cerebellum under longitudinal behavioral manipulations.

scholarly journals Spike burst–pause dynamics of Purkinje cells regulate sensorimotor adaptation

2018 ◽  
Author(s):  
Niceto R. Luque ◽  
Francisco Naveros ◽  
Richard R. Carrillo ◽  
Eduardo Ros ◽  
Angelo Arleo
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Vestibular Nuclei ◽  
Response Patterns ◽  
Spike Burst ◽  
Vor Adaptation ◽  
Cell Firing ◽  
Cerebellar Purkinje Cells ◽  
Oculomotor Adaptation

AbstractCerebellar Purkinje cells mediate accurate eye movement coordination. However, it remains unclear how oculomotor adaptation depends on the interplay between the characteristic Purkinje cell response patterns, namely tonic, bursting, and spike pauses. Here, a spiking cerebellar model assesses the role of Purkinje cell firing patterns in vestibular ocular reflex (VOR) adaptation. The model captures the cerebellar microcircuit properties and it incorporates spike-based synaptic plasticity at multiple cerebellar sites. A detailed Purkinje cell model reproduces the three spike-firing patterns that are shown to regulate the cerebellar output. Our results suggest that pauses following Purkinje complex spikes (bursts) encode transient disinhibition of targeted medial vestibular nuclei, critically gating the vestibular signals conveyed by mossy fibres. This gating mechanism accounts for early and coarse VOR acquisition, prior to the late reflex consolidation. In addition, properly timed and sized Purkinje cell bursts allow the ratio between long-term depression and potentiation (LTD/LTP) to be finely shaped at mossy fibre-medial vestibular nuclei synapses, which optimises VOR consolidation. Tonic Purkinje cell firing maintains the consolidated VOR through time. Importantly, pauses are crucial to facilitate VOR phase-reversal learning, by reshaping previously learnt synaptic weight distributions. Altogether, these results predict that Purkinje spike burst-pause dynamics are instrumental to VOR learning and reversal adaptation.Author SummaryCerebellar Purkinje cells regulate accurate eye movement coordination. However, it remains unclear how cerebellar-dependent oculomotor adaptation depends on the interplay between Purkinje cell characteristic response patterns: tonic, high-frequency bursting, and post-complex spike pauses. We explore the role of Purkinje spike burst-pause dynamics in VOR adaptation. A biophysical model of Purkinje cell is at the core of a spiking network model, which captures the cerebellar microcircuit properties and incorporates spike-based synaptic plasticity mechanisms at different cerebellar sites. We show that Purkinje spike burst-pause dynamics are critical for (1) gating the vestibular-motor response association during VOR acquisition; (2) mediating the LTD/LTP balance for VOR consolidation; (3) reshaping synaptic efficacy distributions for VOR phase-reversal adaptation; (4) explaining the reversal VOR gain discontinuities during sleeping.

scholarly journals Gating by Functionally Indivisible Cerebellar Circuits: a Hypothesis

2021 ◽  
Author(s):  
Mike Gilbert ◽  
Chris Miall
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cell ◽  
Supervised Learning ◽  
Purkinje Cells ◽  
Alternative Model ◽  
Learning Algorithm ◽  
Projection Neurons ◽  
Learning Models ◽  
Central Idea ◽  
Cell Firing

AbstractThe attempt to understand the cerebellum has been dominated for years by supervised learning models. The central idea is that a learning algorithm modifies transmission strength at repeatedly co-active synapses, creating memories stored as finely calibrated synaptic weights. As a result, Purkinje cells, usually the de facto output cells of these models, acquire a modified response to input in a remembered pattern. This paper proposes an alternative model of pattern memory in which the function of a match is permissive, allowing but not driving output, and accordingly controlling the timing of output but not the rate of firing by Purkinje cells. Learning does not result in graded synaptic weights. There is no supervised learning algorithm or memory of individual patterns, which, like graded weights, are unnecessary to explain the evidence. Instead, patterns are classed as simply either known or not, at the level of input to a functional population of 100s of Purkinje cells (a microzone). The standard is strict. If only a handful of Purkinje cells receive a mismatch output of the whole circuit is blocked. Only if there is a full and accurate match are projection neurons in deep nuclei, which carry the output of most circuits, released from default inhibitory restraint. Purkinje cell firing at those times is a linear function of input rates. There is no effect of modification of synaptic transmission except to either allow or block output.

Dynamic Synchronization of Purkinje Cell Simple Spikes

2006 ◽  
Vol 96 (6) ◽  
pp. 3485-3491 ◽  
Author(s):  
Soon-Lim Shin ◽  
Erik De Schutter
Keyword(s):  
Purkinje Cell ◽  
Firing Rate ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Cerebellar Nuclei ◽  
Temporal Coding ◽  
Sharp Peak ◽  
Deep Cerebellar Nuclei

Purkinje cells (PCs) integrate all computations performed in the cerebellar cortex to inhibit neurons in the deep cerebellar nuclei (DCN). Simple spikes recorded in vivo from pairs of PCs separated by <100 μm are known to be synchronized with a sharp peak riding on a broad peak, but the significance of this finding is unclear. We show that the sharp peak consists exclusively of simple spikes associated with pauses in firing. The broader, less precise peak was caused by firing-rate co-modulation of faster firing spikes. About 13% of all pauses were synchronized, and these pauses had a median duration of 20 ms. As in vitro studies have reported that synchronous pauses can reliably trigger spikes in DCN neurons, we suggest that the subgroup of spikes causing the sharp peak is important for precise temporal coding in the cerebellum.

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