scholarly journals Functional convergence of autonomic and sensorimotor processing in the lateral cerebellum

2019 ◽  
Author(s):  
Vincenzo Romano ◽  
Aoibhinn L. Reddington ◽  
Silvia Cazzanelli ◽  
Mario Negrello ◽  
Laurens W.J. Bosman ◽  
...  

The cerebellum is involved in control of voluntary and autonomic rhythmic behaviors, yet it is largely unclear to what extent it coordinates these in a concerted action. Here, we studied Purkinje cell activity during unperturbed and perturbed respiration in cerebellar lobules simplex, crus 1 and 2. During unperturbed (eupneic) respiration complex spike and simple spike activity encoded respiratory activity, the timing of which corresponded with ongoing sensorimotor feedback. Instead, upon whisker stimulation mice concomitantly accelerated their simple spike activity and inspiration in a phase-dependent manner. Moreover, the accelerating impact of whisker stimulation on respiration could be mimicked by optogenetic stimulation of Purkinje cells and prevented by cell-specific genetic modification of their AMPA receptors that hampered increases in simple spike firing. Thus, the impact of Purkinje cell activity on respiratory control is context- and phase-dependent, suggesting a coordinating role for the cerebellar hemispheres in aligning autonomic and sensorimotor behaviors.

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.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Vincenzo Romano ◽  
Licia De Propris ◽  
Laurens WJ Bosman ◽  
Pascal Warnaar ◽  
Michiel M ten Brinke ◽  
...  

Cerebellar 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 behavioral responses. Neuronal and behavioral changes did not occur in two cell-specific mouse models with impaired long-term potentiation at their 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.


2011 ◽  
Vol 437 (2) ◽  
pp. 215-222 ◽  
Author(s):  
Christopher G. R. Perry ◽  
Daniel A. Kane ◽  
Chien-Te Lin ◽  
Rachel Kozy ◽  
Brook L. Cathey ◽  
...  

Assessment of mitochondrial ADP-stimulated respiratory kinetics in PmFBs (permeabilized fibre bundles) is increasingly used in clinical diagnostic and basic research settings. However, estimates of the Km for ADP vary considerably (~20–300 μM) and tend to overestimate respiration at rest. Noting that PmFBs spontaneously contract during respiration experiments, we systematically determined the impact of contraction, temperature and oxygenation on ADP-stimulated respiratory kinetics. BLEB (blebbistatin), a myosin II ATPase inhibitor, blocked contraction under all conditions and yielded high Km values for ADP of >~250 and ~80 μM in red and white rat PmFBs respectively. In the absence of BLEB, PmFBs contracted and the Km for ADP decreased ~2–10-fold in a temperature-dependent manner. PmFBs were sensitive to hyperoxia (increased Km) in the absence of BLEB (contracted) at 30 °C but not 37 °C. In PmFBs from humans, contraction elicited high sensitivity to ADP (Km<100 μM), whereas blocking contraction (+BLEB) and including a phosphocreatine/creatine ratio of 2:1 to mimic the resting energetic state yielded a Km for ADP of ~1560 μM, consistent with estimates of in vivo resting respiratory rates of <1% maximum. These results demonstrate that the sensitivity of muscle to ADP varies over a wide range in relation to contractile state and cellular energy charge, providing evidence that enzymatic coupling of energy transfer within skeletal muscle becomes more efficient in the working state.


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

2018 ◽  
Vol 25 (3) ◽  
pp. 241-257 ◽  
Author(s):  
Laurentiu S. Popa ◽  
Martha L. Streng ◽  
Timothy J. Ebner

Fundamental for understanding cerebellar function is determining the representations in Purkinje cell activity, the sole output of the cerebellar cortex. Up to the present, the most accurate descriptions of the information encoded by Purkinje cells were obtained in the context of motor behavior and reveal a high degree of heterogeneity of kinematic and performance error signals encoded. The most productive framework for organizing Purkinje cell firing representations is provided by the forward internal model hypothesis. Direct tests of this hypothesis show that individual Purkinje cells encode two different forward models simultaneously, one for effector kinematics and one for task performance. Newer results demonstrate that the timing of simple spike encoding of motor parameters spans an extend interval of up to ±2 seconds. Furthermore, complex spike discharge is not limited to signaling errors, can be predictive, and dynamically controls the information in the simple spike firing to meet the demands of upcoming behavior. These rich, diverse, and changing representations highlight the integrative aspects of cerebellar function and offer the opportunity to generalize the cerebellar computational framework over both motor and non-motor domains.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247801
Author(s):  
Friederike Auer ◽  
Eliana Franco Taveras ◽  
Uli Klein ◽  
Céline Kesenheimer ◽  
Dana Fleischhauer ◽  
...  

Modulation of neuronal excitability is a prominent way of shaping the activity of neuronal networks. Recent studies highlight the role of calcium-activated chloride currents in this context, as they can both increase or decrease excitability. The calcium-activated chloride channel Anoctamin 2 (ANO2 alias TMEM16B) has been described in several regions of the mouse brain, including the olivo-cerebellar system. In inferior olivary neurons, ANO2 was proposed to increase excitability by facilitating the generation of high-threshold calcium spikes. An expression of ANO2 in cerebellar Purkinje cells was suggested, but its role in these neurons remains unclear. In the present study, we confirmed the expression of Ano2 mRNA in Purkinje cells and performed electrophysiological recordings to examine the influence of ANO2-chloride channels on the excitability of Purkinje cells by comparing wildtype mice to mice lacking ANO2. Recordings were performed in acute cerebellar slices of adult mice, which provided the possibility to study the role of ANO2 within the cerebellar cortex. Purkinje cells were uncoupled from climbing fiber input to assess specifically the effect of ANO2 channels on Purkinje cell activity. We identified an attenuating effect of ANO2-mediated chloride currents on the instantaneous simple spike activity both during strong current injections and during current injections close to the simple spike threshold. Moreover, we report a reduction of inhibitory currents from GABAergic interneurons upon depolarization, lasting for several seconds. Together with the role of ANO2-chloride channels in inferior olivary neurons, our data extend the evidence for a role of chloride-dependent modulation in the olivo-cerebellar system that might be important for proper cerebellum-dependent motor coordination and learning.


2020 ◽  
Author(s):  
Skyler L. Jackman ◽  
Christopher H. Chen ◽  
Heather L. Offermann ◽  
Iain R. Drew ◽  
Bailey M. Harrison ◽  
...  

AbstractAlthough the cerebellum is traditionally associated with balance and motor function, it also plays wider roles in affective and cognitive behaviors. Evidence suggests that the cerebellar vermis may regulate aggressive behavior, though the cerebellar circuits and patterns of activity that influence aggression remain unclear. We used optogenetic methods to bidirectionally modulate the activity of spatially-delineated cerebellar Purkinje cells to evaluate the impact on aggression in mice. Increasing Purkinje cell activity in the vermis significantly reduced the frequency of attacks in a resident-intruder assay. Reduced aggression was not a consequence of impaired motor function, because optogenetic stimulation did not alter motor performance. In complementary experiments, optogenetic inhibition of Purkinje cells in the vermis increased the frequency of attacks. These results establish Purkinje cell activity in the cerebellar vermis regulates aggression, and further support the importance of the cerebellum in driving affective behaviors that could contribute to neurological disorders.


2015 ◽  
Vol 113 (7) ◽  
pp. 2524-2536 ◽  
Author(s):  
Haibo Zhou ◽  
Kai Voges ◽  
Zhanmin Lin ◽  
Chiheng Ju ◽  
Martijn Schonewille

The massive computational capacity of the cerebellar cortex is conveyed by Purkinje cells onto cerebellar and vestibular nuclei neurons through their GABAergic, inhibitory output. This implies that pauses in Purkinje cell simple spike activity are potentially instrumental in cerebellar information processing, but their occurrence and extent are still heavily debated. The cerebellar cortex, although often treated as such, is not homogeneous. Cerebellar modules with distinct anatomical connectivity and gene expression have been described, and Purkinje cells in these modules also differ in firing rate of simple and complex spikes. In this study we systematically correlate, in awake mice, the pausing in simple spike activity of Purkinje cells recorded throughout the entire cerebellum, with their location in terms of lobule, transverse zone, and zebrin-identified cerebellar module. A subset of Purkinje cells displayed long (>500-ms) pauses, but we found that their occurrence correlated with tissue damage and lower temperature. In contrast to long pauses, short pauses (<500 ms) and the shape of the interspike interval (ISI) distributions can differ between Purkinje cells of different lobules and cerebellar modules. In fact, the ISI distributions can differ both between and within populations of Purkinje cells with the same zebrin identity, and these differences are at least in part caused by differential synaptic inputs. Our results suggest that long pauses are rare but that there are differences related to shorter intersimple spike intervals between and within specific subsets of Purkinje cells, indicating a potential further segregation in the activity of cerebellar Purkinje cells.


1983 ◽  
Vol 49 (3) ◽  
pp. 745-766 ◽  
Author(s):  
J. M. Bower ◽  
D. C. Woolston

1. We compared the spatial pattern of shortest latency somatosensory (tactile) projections to the Purkinje cell (PC) layer and to the underlying granule cell (GC) layer in tactile areas of rat cerebellar cortex. Micro-mapping methods were used to sample single units in the PC layer and multiple units in the GC layer of both anesthetized and unanesthetized rats. Mechanical and electrical stimulation of the body surface were employed. Responsiveness of PCs to cutaneous stimulation was assessed by constructing histograms of simple spike activity and statistically comparing poststimulus activity to nonstimulated base-line PC activity. 2. We found that PCs respond to tactile stimulation with increases (7-10 ms) followed by decreases (8-15 ms) in simple spike activity. Increases in simple spike activity followed activation of the underlying GC layer by 1-4 ms, while decreases in simple spike activity were found 2-5 ms after GC layer activation. 3. PCs were found to have both excitatory and inhibitory receptive fields (RFs). Excitatory RFs were restricted to small areas of a single body part and for each PC were very similar or identical to the RFs of neurons in the immediately subjacent GC layer. Inhibitory PC RFs were larger, often containing more than one body part and for each PC, were only partially similar to the RFs of subjacent GCs. PC inhibitory RFs also often included body surfaces projecting to the nearby but not to the underlying GC layer. 4. Stimulation of a single peripheral locus resulted in small, distinct regions of PC layer excitation and inhibition. Areas of PC excitation overlie activated regions of the GC layer, while inhibited PCs overlie both activated and nonactivated GC regions. 5. We found PCs to be organized in groups or patches with respect to the specific body region that was capable of activating them (upper lip, lower lip, etc.). Adjacent patches of PCs often represented widely separated body parts. This pattern of PC layer activating RF projections was congruent with the pattern of excitatory RF projections to the underlying GC layer. 6. These results indicate that there is a vertical organization in GC-PC excitatory relations, while GC-induced PC inhibition is slightly more widely distributed. 7. Our finding that the patchlike activation of PCs is congruent with that of the underlying GC layer contrasts with the classical concept that PCs are activated by parallel fibers in a "beamlike" fashion from a patch of GCs. Thus, a reevaluation of the role of parallel fibers seems to us to be in order. 8. In conclusion, our results support the view that short-latency afferent tactile projections to both the GC and PC layers of cerebellar cortex are highly organized spatially. This specificity of body surface projections must be incorporated into modern views of the functional organization of cerebellar cortex.


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