scholarly journals A Novel FN-MdV Pathway and Its Role in Cerebellar Multimodular Control of Sensorimotor Behavior

2020 ◽  
Author(s):  
Xiaolu Wang ◽  
Si-yang Yu ◽  
Zhong Ren ◽  
Chris De Zeeuw ◽  
Zhenyu Gao
Keyword(s):  
Purkinje Cells ◽  
Motor Neurons ◽  
Eyeblink Conditioning ◽  
Fastigial Nucleus ◽  
Reticular Nucleus ◽  
Eyelid Closure ◽  
Interposed Nucleus ◽  
Conditioned Responses ◽  
Cerebellar Modules ◽  
Synergistic Modulation

Abstract The cerebellum is crucial for various associative sensorimotor behaviors. Delay eyeblink conditioning (DEC) depends on the simplex lobule-interposed nucleus (IN) pathway, yet it is unclear how other cerebellar modules cooperate during this task. Here, we demonstrate the contribution of the vermis-fastigial nucleus (FN) pathway in controlling DEC. We found that task-related modulations in vermal Purkinje cells and FN neurons predict conditioned responses (CRs). Coactivation of the FN and the IN allows for the generation of proper motor commands for CRs, but only FN output fine-tunes unconditioned responses. The vermis-FN pathway launches its signal via the contralateral ventral medullary reticular nucleus, which converges with the command from the simplex-IN pathway onto facial motor neurons. We propose that the IN pathway specifically drives CRs whereas the FN pathway modulates the amplitudes of eyelid closure during DEC. Thus, associative sensorimotor task optimization requires synergistic modulation of different olivocerebellar modules that provide unique contributions.

scholarly journals A FN-MdV pathway and its role in cerebellar multimodular control of sensorimotor behavior

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaolu Wang ◽  
Si-yang Yu ◽  
Zhong Ren ◽  
Chris I. De Zeeuw ◽  
Zhenyu Gao
Keyword(s):  
Purkinje Cells ◽  
Motor Neurons ◽  
Eyeblink Conditioning ◽  
Fastigial Nucleus ◽  
Reticular Nucleus ◽  
Eyelid Closure ◽  
Interposed Nucleus ◽  
Conditioned Responses ◽  
Cerebellar Modules ◽  
Synergistic Modulation

AbstractThe cerebellum is crucial for various associative sensorimotor behaviors. Delay eyeblink conditioning (DEC) depends on the simplex lobule-interposed nucleus (IN) pathway, yet it is unclear how other cerebellar modules cooperate during this task. Here, we demonstrate the contribution of the vermis-fastigial nucleus (FN) pathway in controlling DEC. We found that task-related modulations in vermal Purkinje cells and FN neurons predict conditioned responses (CRs). Coactivation of the FN and the IN allows for the generation of proper motor commands for CRs, but only FN output fine-tunes unconditioned responses. The vermis-FN pathway launches its signal via the contralateral ventral medullary reticular nucleus, which converges with the command from the simplex-IN pathway onto facial motor neurons. We propose that the IN pathway specifically drives CRs, whereas the FN pathway modulates the amplitudes of eyelid closure during DEC. Thus, associative sensorimotor task optimization requires synergistic modulation of different olivocerebellar modules each provide unique contributions.

scholarly journals A recurrent circuit links antagonistic cerebellar modules during associative motor learning

2021 ◽  
Author(s):  
Shogo Ohmae ◽  
Keiko Ohmae ◽  
Shane A Heiney ◽  
Divya Subramanian ◽  
Javier F Medina
Keyword(s):  
Purkinje Cells ◽  
Functional Organization ◽  
Eyeblink Conditioning ◽  
Recurrent Network ◽  
Basic Operation ◽  
Conventional View ◽  
Neural Architecture ◽  
Recurrent Network Dynamics ◽  
Cerebellar Modules ◽  
Specific Error

The neural architecture of the cerebellum is thought to be specialized for performing supervised learning: specific error-related climbing fiber inputs are used to teach sensorimotor associations to small ensembles of Purkinje cells located in functionally distinct modules that operate independently of each other in a purely feedforward manner. Here, we test whether the basic operation of the cerebellum complies with this basic architecture in mice that learned a simple sensorimotor association during eyeblink conditioning. By recording Purkinje cells in different modules and testing whether their responses rely on recurrent circuits, our results reveal three operational principles about the functional organization of the cerebellum that stand in stark contrast to the conventional view: (1) Antagonistic organization, (2) Recurrent network dynamics, and (3) Intermodular communication. We propose that the neural architecture of the cerebellum implements these three operational principles to achieve optimal performance and solve a number of problems in motor control.

scholarly journals Differential spatiotemporal development of Purkinje cell populations and cerebellum-dependent sensorimotor behaviors

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Gerrit Cornelis Beekhof ◽  
Catarina Osório ◽  
Joshua J White ◽  
Scott van Zoomeren ◽  
Hannah van der Stok ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Eyeblink Conditioning ◽  
Rapid Development ◽  
Modular Organization ◽  
Cell Populations ◽  
Activity Levels ◽  
Firing Activity ◽  
The Core ◽  
Cerebellar Modules

Distinct populations of Purkinje cells (PCs) with unique molecular and connectivity features are at the core of the modular organization of the cerebellum. Previously, we showed that firing activity of Purkinje cells differs between ZebrinII-positive (Z+) and -negative (Z−) cerebellar modules (Zhou et al., 2014; Wu et al., 2019). Here, we investigate the timing and extent of PC differentiation during development in mice. We found that several features of PCs, including activity levels, dendritic arborisation, axonal shape and climbing fiber input, develop differentially between nodular and anterior PC populations. Although all PCs show a particularly rapid development in the second postnatal week, anterior PCs typically have a prolonged physiological and dendritic maturation. In line herewith, younger mice exhibit attenuated anterior-dependent eyeblink conditioning, but faster nodular-dependent compensatory eye movement adaptation. Our results indicate that specific cerebellar regions have unique developmental timelines which match with their related, specific forms of cerebellum-dependent behaviors.

EVIDENCE FOR THE EXISTENCE OF FOUR TYPES OF RIBONUCLEOPROTEIN IN THE NERVE CELLS OF THE CEREBELLUM IN THE ADULT CAT

1965 ◽  
Vol 43 (2) ◽  
pp. 357-367 ◽  
Author(s):  
L. A. Chouinard
Keyword(s):  
Purkinje Cells ◽  
Toluidine Blue ◽  
Ganglion Cells ◽  
Observational Evidence ◽  
Fastigial Nucleus ◽  
Staining Procedure ◽  
Ground Substance ◽  
Ribonucleic Acids ◽  
Nucleolar Apparatus ◽  
Adult Cat

In Helly-fixed cerebella, the toluidine blue – molybdate staining procedure reveals the existence of four distinct types of ribonucleoprotein in both the Purkinje cells of the vermian zone and the multipolar ganglion cells of the fastigial nucleus. These four types of ribonucleoprotein are found in, respectively, the ground substance (nucleolar matrix) of the nucleolus, the intranucleolar vacuoles (nucleolini), the intranuclear paranucleolar masses, and the cytoplasmic Nissl bodies. The relevant observational evidence suggests that the two organelles of the nucleolar apparatus, that is, the nucleolus and paranucleolar masses together with their associated chromocenters, are concerned with distinct synthetic activities with regard to the elaboration of neuronal ribonucleic acids or ribonucleoproteins. The significance of the above findings is discussed in the light of current concepts pertaining to cellular ribonucleoprotein metabolism.

scholarly journals Stereotyped spatial patterns of functional synaptic connectivity in the cerebellar cortex

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Antoine M Valera ◽  
Francesca Binda ◽  
Sophie A Pawlowski ◽  
Jean-Luc Dupont ◽  
Jean-François Casella ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Granule Cell ◽  
Motor Coordination ◽  
Molecular Layer ◽  
Granule Cell Layer ◽  
Synaptic Organization ◽  
Cerebellar Modules ◽  
Activity Dependent

Motor coordination is supported by an array of highly organized heterogeneous modules in the cerebellum. How incoming sensorimotor information is channeled and communicated between these anatomical modules is still poorly understood. In this study, we used transgenic mice expressing GFP in specific subsets of Purkinje cells that allowed us to target a given set of cerebellar modules. Combining in vitro recordings and photostimulation, we identified stereotyped patterns of functional synaptic organization between the granule cell layer and its main targets, the Purkinje cells, Golgi cells and molecular layer interneurons. Each type of connection displayed position-specific patterns of granule cell synaptic inputs that do not strictly match with anatomical boundaries but connect distant cortical modules. Although these patterns can be adjusted by activity-dependent processes, they were found to be consistent and predictable between animals. Our results highlight the operational rules underlying communication between modules in the cerebellar cortex.

scholarly journals Changes in membrane properties of rat deep cerebellar nuclear projection neurons during acquisition of eyeblink conditioning

2018 ◽  
Vol 115 (40) ◽  
pp. E9419-E9428 ◽  
Author(s):  
Desheng Wang ◽  
Carrie A. Smith-Bell ◽  
Lauren B. Burhans ◽  
Deidre E. O’Dell ◽  
Roger W. Bell ◽  
...  
Keyword(s):  
Pseudorabies Virus ◽  
Eyeblink Conditioning ◽  
Cerebellar Nuclei ◽  
Membrane Properties ◽  
Projection Neurons ◽  
Adult Rats ◽  
Electrophysiological Properties ◽  
Conditioned Responses ◽  
Sensory Nervous System ◽  
Whole Cell Recordings

Previous studies have shown changes in membrane properties of neurons in rat deep cerebellar nuclei (DCN) as a function of development, but due to technical difficulties in obtaining viable DCN slices from adult animals, it remains unclear whether there are learning-related alterations in the membrane properties of DCN neurons in adult rats. This study was designed to record from identified DCN cells in cerebellar slices from postnatal day 25–26 (P25–26) rats that had a relatively mature sensory nervous system and were able to acquire learning as a result of tone–shock eyeblink conditioning (EBC) and to document resulting changes in electrophysiological properties. After electromyographic electrode implantation at P21 and inoculation with a fluorescent pseudorabies virus (PRV-152) at P22–23, rats received either four sessions of paired delay EBC or unpaired stimulus presentations with a tone conditioned stimulus and a shock unconditioned stimulus or sat in the training chamber without stimulus presentations. Compared with rats given unpaired stimuli or no stimulus presentations, rats given paired EBC showed an increase in conditioned responses across sessions. Whole-cell recordings of both fluorescent and nonfluorescent DCN projection neurons showed that delay EBC induced significant changes in membrane properties of evoked DCN action potentials including a reduced after-hyperpolarization amplitude and shortened latency. Similar findings were obtained in hyperpolarization-induced rebound spikes of DCN neurons. In sum, delay EBC produced significant changes in the membrane properties of juvenile rat DCN projection neurons. These learning-specific changes in DCN excitability have not previously been reported in any species or task.

Saccadic eye movements evoked by microstimulation of the fastigial nucleus of macaque monkeys

1988 ◽  
Vol 60 (3) ◽  
pp. 1036-1052 ◽  
Author(s):  
H. Noda ◽  
S. Murakami ◽  
J. Yamada ◽  
J. Tamada ◽  
Y. Tamaki ◽  
...  
Keyword(s):  
Eye Movements ◽  
White Matter ◽  
Purkinje Cells ◽  
Saccadic Eye Movements ◽  
The Other ◽  
Fastigial Nucleus ◽  
Threshold Region ◽  
Other Hand ◽  
Low Threshold ◽  
Stimulation Of

1. Systematic exploration throughout the deep cerebellar nuclei and white matter disclosed that the region from which saccadic eye movements (saccades) were evoked with weak currents (less than 10 microA) was confined to the fastigial nucleus and the adjacent white matter. 2. When an electrode for stimulation was advanced in the cerebellum, saccades were evoked in the direction of the stimulated side (ipsilateral saccades) as it entered the low-threshold region. In some tracks, particularly when the electrode was advanced in the medial portion of the fastigial nucleus, the direction of the evoked saccades changed from the ipsilateral to the contralateral. 3. The mappings with microstimulation disclosed that the ipsilateral saccades were elicited from a relatively wide region that included almost the full extent of the fastigial nucleus. The low-threshold region continued in the white matter caudally into vermal lobule VII and rostrally into the dorsal aspect of the brachium conjunctivum. On the other hand, the contralateral saccades were evoked from a relatively circumscribed region in the ventromedial portion of the fastigial nucleus. 4. The reversal in the direction of the horizontal component occurred always in a narrow zone in the core of the fastigial nucleus. The caudal part of this zone coincided with an ellipsoidal region where anterogradely labeled axons of the Purkinje cells terminated when HRP was injected into vermal lobule VII. 5. When bicuculline (0.2-1 microgram) was injected in the ellipsoidal region, the ipsilateral saccades evoked from the dorsocaudal aspect of the region were suppressed for several hours. On the other hand, the contralateral saccades evoked from the ventromedial portion of the fastigial nucleus were either unchanged or enhanced. 6. Because the ipsilateral saccades were suppressed by bicuculline, they were most probably evoked by stimulation of the presynaptic component of gamma-amino-butyric acid-(GABA) mediated synapses, namely the axons of Purkinje cells. 7. Because stimulation of the presynaptic component of the inhibitory synapses evoked ipsilateral saccades, activation of the postsynaptic component would evoke contralateral saccades. In fact, the distribution of the fastigial sites yielding contralateral saccades coincided with the course of axons of fastigial neurons arising in the ellipsoidal region. It is most likely, therefore, that the contralateral saccades were evoked by stimulation of fastigial neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Loss of the nucleoporin Aladin in central nervous system and fibroblasts of Allgrove Syndrome

2019 ◽  
Vol 28 (23) ◽  
pp. 3921-3927 ◽  
Author(s):  
Giacomo Bitetto ◽  
Dario Ronchi ◽  
Sara Bonato ◽  
Alessandra Pittaro ◽  
Giacomo Monzio Compagnoni ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Purkinje Cells ◽  
Motor Neurons ◽  
Nuclear Membrane ◽  
Nucleocytoplasmic Transport ◽  
Neurological Involvement ◽  
Nuclear Pore ◽  
Striatal Neurons ◽  
Allgrove Syndrome

Abstract Allgrove syndrome (AS) is a rare disease with broad neurological involvement. Neurodegeneration can affect spinal motor neurons, Purkinje cells, striatal neurons and the autonomic system. The mechanisms that lead to neuronal loss are still unclear. Recessive mutations in the AAAS gene affect the encoded protein Aladin, which would normally localize to the cytoplasmic face of the nuclear membrane as part of the nuclear pore complex (NPC). While the NPC is known to be a key factor for nucleocytoplasmic transport, the precise role of Aladin has not been elucidated yet. Here, we explored the consequences of the homozygous AAAS mutation c.464G>A (p.R155H) in central nervous system tissues and fibroblasts of a novel AS patient presenting motor neuron disease, cerebellar ataxia and autonomic dysfunction. Neuropathological analyses showed severe loss of motor neurons and Purkinje cells, with significant reduction in the perinuclear expression of Aladin. A reduced amount of protein was detected in the nuclear membrane fraction of the patient’s brain. RNA analysis revealed a significant reduction of the transcript AAAS-1, while the AAAS-2 transcript was upregulated in fibroblasts. To our knowledge, this is the first study to demonstrate the effects of AAAS mutations in the human central nervous system.

Enhanced Synaptic Transmission in CA1 Hippocampus After Eyeblink Conditioning

1997 ◽  
Vol 78 (2) ◽  
pp. 1184-1187 ◽  
Author(s):  
John M. Power ◽  
Lucien T. Thompson ◽  
James R. Moyer ◽  
John F. Disterhoft
Keyword(s):  
Synaptic Transmission ◽  
Repeated Measures ◽  
Eyeblink Conditioning ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Trace Conditioning ◽  
Excitatory Postsynaptic Potential ◽  
Field Potentials ◽  
Repeated Measures Analysis ◽  
Conditioned Responses

Power, John M., Lucien T. Thompson, James R. Moyer, Jr., and John F. Disterhoft. Enhanced synaptic transmission in CA1 hippocampus after eyeblink conditioning. J. Neurophysiol. 78: 1184–1187, 1997. CA1 field potentials evoked by Schaffer collateral stimulation of hippocampal slices from trace-conditioned rabbits were compared with those from naive and pseudoconditioned controls. Conditioned rabbits received 80 trace conditioning trials daily until reaching a criterion of 80% conditioned responses in a session. Hippocampal slices were prepared 1 or 24 h after reaching criterion (for trace-conditioned animals) or after a final unpaired stimulus session (for pseudoconditioned animals); naive animals were untrained. Both somatic and dendritic field potentials were recorded in response to various stimulus durations. Recording and data reduction were performed blind to the conditioning state of the rabbit. The excitatory postsynaptic potential slope was greater in slices prepared from trace-conditioned animals killed 1 h after conditioning than in naive and pseudoconditioned controls (repeated-measures analysis of variance, F = 4.250, P < 0.05). Associative learning specifically enhanced synaptic transmission between CA3 and CA1 immediately after training. This effect was not evident in the population field potential measured 24 h later.

scholarly journals Effects of working memory load and CS-US intervals on delay eyeblink conditioning

2020 ◽  
Author(s):  
Leila Etemadi ◽  
Dan-Anders jirenhed ◽  
Anders Rasmussen
Keyword(s):  
Working Memory ◽  
Interstimulus Interval ◽  
Memory Load ◽  
Eyeblink Conditioning ◽  
Working Memory Load ◽  
Linear Mixed Effects Model ◽  
Linear Mixed Effects ◽  
Cerebellar Function ◽  
Conditioning Data ◽  
Conditioned Responses

Background: Eyeblink conditioning is used in many different species to study motor learning and make inferences about cerebellar function. However, considerable discrepancies in performance between different species combined with evidence that awareness of stimulus contingencies affects performance indicates that eyeblink conditioning in part reflects activity in non-cerebellar regions. This questions whether eyeblink conditioning can be used as a pure measure of cerebellar function in humans. Methods: Here we explored two ways to reduce non-cerebellar influences on performance in eyeblink conditioning: (1) using a short interstimulus interval, and (2) having participants do working memory tasks during the conditioning. Data were analyzed, and the influence of the interstimulus interval and working memory tasks was assessed using a linear mixed effects model. Results: Our results show that subjects trained with a short interstimulus interval (150ms and 250ms) produce few conditioned responses after 100 trials. For subjects trained with a longer interstimulus interval (500ms), those who did working memory tasks produced fewer conditioned responses and had a more gradual learning curve, more akin to those reported in the animal literature. Conclusions: Our results suggest that having subjects perform working memory tasks during eyeblink conditioning can be a viable strategy to reduce non-cerebellar interference in the learning.

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