Synaptic excitation by climbing fibre collaterals in the cerebellar nuclei of juvenile and adult mice

AbstractMost studies investigating the impact of cerebral cortex (CC) onto the cerebellum highlight the role of the pontine mossy fibre system. However, cerebro-cerebellar communication may also be mediated by the olivary climbing fibres via a hub in the mesodiencephalic junction (MDJ). Here, we show that rostromedial and caudal parts of mouse CC predominantly project to the principal olive via the rostroventral MDJ and that more rostrolateral CC regions prominently project to the rostral medial accessory olive via the caudodorsal MDJ. Moreover, transneuronal tracing results show that the cerebellar nuclei innervate the olivary-projecting neurons in the MDJ that receive input from CC, and that they adhere to the same topographical relations. By unravelling these topographic and dense, mono- and disynaptic projections from the CC through the MDJ and inferior olive to the cerebellum, this work establishes that cerebro-cerebellar communication can be mediated by both the mossy fibre and climbing fibre system.

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Climbing Fibre “Collateral” Innervation of The Central Cerebellar Nuclei Studied with Anterograde Phaseolus Vulgaris-Leucoagglutinin (PHA-L) Labelling

The Olivocerebellar System in Motor Control ◽

10.1007/978-3-642-73920-0_8 ◽

1989 ◽

pp. 82-85

Author(s):

J. J. L. Want ◽

M. Guegan ◽

L. Wiklund ◽

C. Buisseret-Delmas ◽

T. H. Ruigrok ◽

...

Keyword(s):

Phaseolus Vulgaris ◽

Cerebellar Nuclei ◽

Climbing Fibre ◽

Phaseolus Vulgaris Leucoagglutinin

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Neuregulin signaling mediates the acute and sustained antidepressant effects of subanesthetic ketamine

Translational Psychiatry ◽

10.1038/s41398-021-01255-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Steven F. Grieco ◽

Xin Qiao ◽

Kevin G. Johnston ◽

Lujia Chen ◽

Renetta R. Nelson ◽

...

Keyword(s):

Neural Plasticity ◽

Cortical Plasticity ◽

Forced Swim Test ◽

Inhibitory Neurons ◽

Neuregulin 1 ◽

Synaptic Excitation ◽

Adult Mice ◽

Antidepressant Effects ◽

Erbb4 Receptor ◽

Antidepressant Action

AbstractSubanesthetic ketamine evokes rapid antidepressant effects in human patients that persist long past ketamine’s chemical half-life of ~2 h. Ketamine’s sustained antidepressant action may be due to modulation of cortical plasticity. We find that ketamine ameliorates depression-like behavior in the forced swim test in adult mice, and this depends on parvalbumin-expressing (PV) neuron-directed neuregulin-1 (NRG1)/ErbB4 signaling. Ketamine rapidly downregulates NRG1 expression in PV inhibitory neurons in mouse medial prefrontal cortex (mPFC) following a single low-dose ketamine treatment. This NRG1 downregulation in PV neurons co-tracks with the decreases in synaptic inhibition to mPFC excitatory neurons for up to a week. This results from reduced synaptic excitation to PV neurons, and is blocked by exogenous NRG1 as well as by PV targeted ErbB4 receptor knockout. Thus, we conceptualize that ketamine’s effects are mediated through rapid and sustained cortical disinhibition via PV-specific NRG1 signaling. Our findings reveal a novel neural plasticity-based mechanism for ketamine’s acute and long-lasting antidepressant effects.

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Sex differences in cerebellar synaptic transmission and sex-specific responses to autism-linked Gabrb3 mutations in mice

eLife ◽

10.7554/elife.07596 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 15

Author(s):

Audrey A Mercer ◽

Kristin J Palarz ◽

Nino Tabatadze ◽

Catherine S Woolley ◽

Indira M Raman

Keyword(s):

Sex Differences ◽

Angelman Syndrome ◽

Cerebellar Nuclei ◽

Spontaneous Firing ◽

Wild Type ◽

Intrinsic Properties ◽

Firing Rates ◽

Synaptic Excitation ◽

Males And Females ◽

Premotor Areas

Neurons of the cerebellar nuclei (CbN) transmit cerebellar signals to premotor areas. The cerebellum expresses several autism-linked genes, including GABRB3, which encodes GABAA receptor β3 subunits and is among the maternal alleles deleted in Angelman syndrome. We tested how this Gabrb3 m-/p+ mutation affects CbN physiology in mice, separating responses of males and females. Wild-type mice showed sex differences in synaptic excitation, inhibition, and intrinsic properties. Relative to females, CbN cells of males had smaller synaptically evoked mGluR1/5-dependent currents, slower Purkinje-mediated IPSCs, and lower spontaneous firing rates, but rotarod performances were indistinguishable. In mutant CbN cells, IPSC kinetics were unchanged, but mutant males, unlike females, showed enlarged mGluR1/5 responses and accelerated spontaneous firing. These changes appear compensatory, since mutant males but not females performed indistinguishably from wild-type siblings on the rotarod task. Thus, sex differences in cerebellar physiology produce similar behavioral output, but provide distinct baselines for responses to mutations.

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Climbing-fibre activation of NMDA receptors in Purkinje cells of adult mice

The Journal of Physiology ◽

10.1113/jphysiol.2007.141531 ◽

2007 ◽

Vol 585 (1) ◽

pp. 91-101 ◽

Cited By ~ 55

Author(s):

Massimiliano Renzi ◽

Mark Farrant ◽

Stuart G. Cull-Candy

Keyword(s):

Nmda Receptors ◽

Purkinje Cells ◽

Climbing Fibre ◽

Adult Mice

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Activity of Cerebellar Nuclei Neurons Correlates with ZebrinII Identity of Their Purkinje Cell Afferents

Cells ◽

10.3390/cells10102686 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2686

Author(s):

Gerrit C. Beekhof ◽

Simona V. Gornati ◽

Cathrin B. Canto ◽

Avraham M. Libster ◽

Martijn Schonewille ◽

...

Keyword(s):

Action Potential ◽

Bimodal Distribution ◽

Cerebellar Nuclei ◽

Firing Frequency ◽

Action Potential Firing ◽

Adult Mice ◽

Electrophysiological Recordings ◽

Potential Firing

Purkinje cells (PCs) in the cerebellar cortex can be divided into at least two main subpopulations: one subpopulation that prominently expresses ZebrinII (Z+), and shows a relatively low simple spike firing rate, and another that hardly expresses ZebrinII (Z–) and shows higher baseline firing rates. Likewise, the complex spike responses of PCs, which are evoked by climbing fiber inputs and thus reflect the activity of the inferior olive (IO), show the same dichotomy. However, it is not known whether the target neurons of PCs in the cerebellar nuclei (CN) maintain this bimodal distribution. Electrophysiological recordings in awake adult mice show that the rate of action potential firing of CN neurons that receive input from Z+ PCs was consistently lower than that of CN neurons innervated by Z– PCs. Similar in vivo recordings in juvenile and adolescent mice indicated that the firing frequency of CN neurons correlates to the ZebrinII identity of the PC afferents in adult, but not postnatal stages. Finally, the spontaneous action potential firing pattern of adult CN neurons recorded in vitro revealed no significant differences in intrinsic pacemaking activity between ZebrinII identities. Our findings indicate that all three main components of the olivocerebellar loop, i.e., PCs, IO neurons and CN neurons, operate at a higher rate in the Z– modules.

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