A novel inhibitory nucleo-cortical circuit controls cerebellar Golgi cell activity

Ankri, Lea; Husson, Zoé; Pietrajtis, Katarzyna; Proville, Rémi; Léna, Clément; Yarom, Yosef; Dieudonné, Stéphane; Uusisaari, Marylka Yoe

doi:10.7554/elife.06262

Cited by 93 publications

(130 citation statements)

References 100 publications

(190 reference statements)

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“…Until recently, the only feedback described in the cerebellar system was that of GoC inhibition of local grCs. More recently it was shown that some neurons of the cerebellar nuclei send collaterals back up to the cerebellar cortex contacting grCs or GoCs (Ankri et al, 2015; Gao et al, 2016; Houck and Person, 2015). Here we establish that feedback is prominent and important in the cerebellum, and establish that the cerebellum is not exclusively a feedforward circuit.…”

Section: Discussionmentioning

confidence: 99%

Purkinje Cell Collaterals Enable Output Signals from the Cerebellar Cortex to Feed Back to Purkinje Cells and Interneurons

Witter

Rudolph

Pressler

et al. 2016

Neuron

121

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Summary Purkinje cells (PCs) provide the sole output from the cerebellar cortex. Although PCs are well characterized on many levels, surprisingly little is known about their axon collaterals and their target neurons within the cerebellar cortex. It has been proposed that PC collaterals transiently control circuit assembly in early development, but it is thought that PC to PC connections are subsequently pruned. Here, we find that all PCs have collaterals in young, juvenile and adult mice. Collaterals are restricted to the parasagittal plane, and most synapses are located in close proximity to PCs. Using optogenetics and electrophysiology we find that in juveniles and adults PCs make synapses onto other PCs, molecular layer interneurons and Lugaro cells, but not onto Golgi cells. These findings establish that PC output can feed back and regulate numerous circuit elements within the cerebellar cortex and is well suited to contribute to processing in parasagittal zones.

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Section: Discussionmentioning

confidence: 99%

Purkinje Cell Collaterals Enable Output Signals from the Cerebellar Cortex to Feed Back to Purkinje Cells and Interneurons

Witter

Rudolph

Pressler

et al. 2016

Neuron

121

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“…During sensorimotor control cerebellar nuclei neurons (CNNs) integrate excitatory inputs mediated by mossy fiber and climbing fiber collaterals with inhibitory input from Purkinje cells (PCs), which form the sole output of the cerebellar cortex [1–6]. CNNs in turn project to various regions inside and outside the olivocerebellar system [7–12]. Glutamatergic CNNs project to different midbrain structures such as the red nucleus, reticular formation or thalamus and/or they project back to the cerebellar cortex [7,8,10,13–15].…”

Section: Introductionmentioning

confidence: 99%

“…Glutamatergic CNNs project to different midbrain structures such as the red nucleus, reticular formation or thalamus and/or they project back to the cerebellar cortex [7,8,10,13–15]. Analogously, glycinergic inhibitory CNNs can also project to the brainstem and provide feedback to the cerebellar cortex, but with different termination patterns [11,12,16,17]. Most gamma-aminobutyric acid (GABA)-ergic projection neurons of the cerebellar nuclei (CN) provide an inhibitory projection to the inferior olive to regulate climbing fiber activity [18–20], while other GABAergic neurons may function as local interneurons [21].…”

Section: Introductionmentioning

confidence: 99%

Whole-Cell Properties of Cerebellar Nuclei Neurons In Vivo

2016

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Cerebellar nuclei neurons integrate sensorimotor information and form the final output of the cerebellum, projecting to premotor brainstem targets. This implies that, in contrast to specialized neurons and interneurons in cortical regions, neurons within the nuclei encode and integrate complex information that is most likely reflected in a large variation of intrinsic membrane properties and integrative capacities of individual neurons. Yet, whether this large variation in properties is reflected in a heterogeneous physiological cell population of cerebellar nuclei neurons with well or poorly defined cell types remains to be determined. Indeed, the cell electrophysiological properties of cerebellar nuclei neurons have been identified in vitro in young rodents, but whether these properties are similar to the in vivo adult situation has not been shown. In this comprehensive study we present and compare the in vivo properties of 144 cerebellar nuclei neurons in adult ketamine-xylazine anesthetized mice. We found regularly firing (N = 88) and spontaneously bursting (N = 56) neurons. Membrane-resistance, capacitance, spike half-width and firing frequency all widely varied as a continuum, ranging from 9.63 to 3352.1 MΩ, from 6.7 to 772.57 pF, from 0.178 to 1.98 ms, and from 0 to 176.6 Hz, respectively. At the same time, several of these parameters were correlated with each other. Capacitance decreased with membrane resistance (R2 = 0.12, P<0.001), intensity of rebound spiking increased with membrane resistance (for 100 ms duration R2 = 0.1503, P = 0.0011), membrane resistance decreased with membrane time constant (R2 = 0.045, P = 0.031) and increased with spike half-width (R2 = 0.023, P<0.001), while capacitance increased with firing frequency (R2 = 0.29, P<0.001). However, classes of neuron subtypes could not be identified using merely k-clustering of their intrinsic firing properties and/or integrative properties following activation of their Purkinje cell input. Instead, using whole-cell parameters in combination with morphological criteria revealed by intracellular labelling with Neurobiotin (N = 18) allowed for electrophysiological identification of larger (29.3–50 μm soma diameter) and smaller (< 21.2 μm) cerebellar nuclei neurons with significant differences in membrane properties. Larger cells had a lower membrane resistance and a shorter spike, with a tendency for higher capacitance. Thus, in general cerebellar nuclei neurons appear to offer a rich and wide continuum of physiological properties that stand in contrast to neurons in most cortical regions such as those of the cerebral and cerebellar cortex, in which different classes of neurons operate in a narrower territory of electrophysiological parameter space. The current dataset will help computational modelers of the cerebellar nuclei to update and improve their cerebellar motor learning and performance models by incorporating the large variation of the in vivo properties of cerebellar nuclei neurons. The cellular complexity of cerebellar nuclei neurons m...

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“…External afferent input could also be processed in a phasespecific manner across oscillatory cycles, and the size and timing of sensory responses [76], as well as the spread of excitation [33], could be influenced by Golgi cell connectivity. In addition, looking at macro-circuits, the nuclear cell influence on Golgi cells firing patterns [77] could also be regulated by the different phases of GCL oscillations. An intriguing mechanism to control the extent of the activated population during oscillations would be a local switch across the Golgi cell interneuron network, as Golgi-Golgi connections can also be inhibitory [78].…”

Section: Local Circuit Interactions In Cerebellar Cortex Rhythmogenesismentioning

confidence: 99%

Gap Junction Modulation of Low-Frequency Oscillations in the Cerebellar Granule Cell Layer

Robinson¹,

Chapman

Courtemanche³

2017

Cerebellum

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Local field potential (LFP) oscillations in the granule cell layer (GCL) of the cerebellar cortex have been identified previously in the awake rat and monkey during immobility. These low-frequency oscillations are thought to be generated through local circuit interactions between Golgi cells and granule cells within the GCL. Golgi cells display rhythmic firing and pacemaking properties, and also are electrically coupled through gap junctions within the GCL. Here, we tested if gap junctions in the rat cerebellar cortex contribute to the generation of LFP oscillations in the GCL. We recorded LFP oscillations under urethane anesthesia, and examined the effects of local infusion of gap junction blockers on 5-15 Hz oscillations. Local infusion of the gap junction blockers carbenoxolone and mefloquine resulted in significant decreases in the power of oscillations over a 30-min period, but the power of oscillations was unchanged in control experiments following vehicle injections. In addition, infusion of gap junction blockers had no significant effect on multi-unit activity, suggesting that the attenuation of low-frequency oscillations was likely due to reductions in electrical coupling rather than a decreased excitability within the granule cell layer. Our results indicate that electrical coupling among the Golgi cell networks in the cerebellar cortex contributes to the local circuit mechanisms that promote the occurrence of GCL LFP slow oscillations in the anesthetized rat.

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A novel inhibitory nucleo-cortical circuit controls cerebellar Golgi cell activity

Cited by 93 publications

References 100 publications

Purkinje Cell Collaterals Enable Output Signals from the Cerebellar Cortex to Feed Back to Purkinje Cells and Interneurons

Purkinje Cell Collaterals Enable Output Signals from the Cerebellar Cortex to Feed Back to Purkinje Cells and Interneurons

Whole-Cell Properties of Cerebellar Nuclei Neurons In Vivo

Gap Junction Modulation of Low-Frequency Oscillations in the Cerebellar Granule Cell Layer

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