Abstract
Stellate cells are inhibitory GABAergic interneurons located in the molecular layer of the cerebellar cortex. Stellate cells receive excitatory glutamatergic inputs from parallel fibers (PF) and climbing fibers, as well as inhibitory GABAergic input from other stellate cells and Purkinje cell axon collaterals (Witter et al. Neuron 91:312–319, 2016). These inhibitory interneurons suppress the activity of Purkinje cells through feed-forward inhibition. A variety of mechanisms regulate GABA release at inhibitory synapses in the cerebellar cortex and consequently alter cerebellum-dependent motor and non-motor functions.
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References
Alcami P, Marty A (2013) Estimating functional connectivity in an electrically coupled interneuron network. Proc Natl Acad Sci 110(49):E4798–E4807. https://doi.org/10.1073/pnas.1310983110
Alviña K, Khodakhah K (2010) KCa channels as therapeutic targets in episodic ataxia type-2. J Neurosci 30(21):7249–7257. https://doi.org/10.1523/JNEUROSCI.6341-09.2010
Arlt C, Häusser M (2020) Microcircuit rules governing impact of single interneurons on Purkinje cell output in vivo. Cell Rep 30(9):3020. https://doi.org/10.1016/j.celrep.2020.02.009
Astorga G, Li D, Therreau L, Kassa M, Marty A, Llano I (2017) Concerted interneuron activity in the cerebellar molecular layer during rhythmic oromotor behaviors. J Neurosci 37(47):11455–11468. https://doi.org/10.1523/JNEUROSCI.1091-17.2017
Beierlein M, Regehr WG (2006) Local interneurons regulate synaptic strength by retrograde release of endocannabinoids. J Neurosci 26(39):9935–9943. https://doi.org/10.1523/JNEUROSCI.0958-06.2006
Bostan AC, Dum RP, Strick PL (2013) Cerebellar networks with the cerebral cortex and basal ganglia. Trends Cogn Sci 17(5):241–254. https://doi.org/10.1016/j.tics.2013.03.003
Browne DL, Gancher ST, Nutt JG, Brunt ER, Smith EA, Kramer P, Litt M (1994) Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nat Genet 8(2):136–140. https://doi.org/10.1038/ng1094-136
Carter AG, Regehr WG (2000) Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse. J Neurosci 20(12):4423–4434
Chadderton P, Margrie TW, Häusser M (2004) Integration of quanta in cerebellar granule cells during sensory processing. Nature 428(6985):856–860. https://doi.org/10.1038/nature02442
Chen S, Augustine GJ, Chadderton P (2017) Serial processing of kinematic signals by cerebellar circuitry during voluntary whisking. Nat Commun 8(1):232. https://doi.org/10.1038/s41467-017-00312-1
Dubois CJ, Liu SJ (2021) GluN2D NMDA receptors gate fear extinction learning and interneuron plasticity. Front Synaptic Neurosci 13:681068. https://doi.org/10.3389/fnsyn.2021.681068
Dubois C, Ramamoorthy P, Whim M, Liu S (2012) Activation of NPY type 5 receptors induces a long-lasting increase in spontaneous GABA release from cerebellar inhibitory interneurons. J Neurophysiol 107(6):1655–1665. https://doi.org/10.1152/jn.00755.2011
Dubois CJ, Lachamp PM, Sun L, Mishina M, Liu SJ (2016) Presynaptic GluN2D receptors detect glutamate spillover and regulate cerebellar GABA release. J Neurophysiol 115(1):271–285. https://doi.org/10.1152/jn.00687.2015
Dubois CJ, Fawcett-Patel J, Katzman PA, Liu SJ (2020) Inhibitory neurotransmission drives endocannabinoid degradation to promote memory consolidation. Nat Commun 11(1):6407. https://doi.org/10.1038/s41467-020-20121-3
Duguid IC, Smart TG (2004) Retrograde activation of presynaptic NMDA receptors enhances GABA release at cerebellar interneuron-Purkinje cell synapses. Nat Neurosci 7(5):525–533. https://doi.org/10.1038/nn1227
Fiskerstrand T et al (2010) Mutations in ABHD12 cause the neurodegenerative disease PHARC: an inborn error of endocannabinoid metabolism. Am J Hum Genet 87(3):410–417. https://doi.org/10.1016/j.ajhg.2010.08.002
Gaffield MA, Christie JM (2017) Movement rate is encoded and influenced by widespread, coherent activity of cerebellar molecular layer interneurons. J Neurosci 37(18):4751–4765. https://doi.org/10.1523/JNEUROSCI.0534-17.2017
Garwicz M, Jorntell H, Ekerot CF (1998) Cutaneous receptive fields and topography of mossy fibres and climbing fibres projecting to cat cerebellar C3 zone. J Physiol 512(Pt 1):277–293. https://doi.org/10.1111/j.1469-7793.1998.277bf.x
Heiney SA, Kim J, Augustine GJ, Medina JF (2014) Precise control of movement kinematics by optogenetic inhibition of Purkinje cell activity. J Neurosci 34(6):2321–2330. https://doi.org/10.1523/JNEUROSCI.4547-13.2014
Herson PS, Virk M, Rustay NR, Bond CT, Crabbe JC, Adelman JP, Maylie J (2003) A mouse model of episodic ataxia type-1. Nat Neurosci 6(4):378–383. https://doi.org/10.1038/nn1025
Hesslow G, Ivarsson M (1994) Suppression of cerebellar Purkinje cells during conditioned responses in ferrets. Neuroreport 5(5):649–652. https://doi.org/10.1097/00001756-199401000-00030
Hoehne A, McFadden MH, DiGregorio DA (2020) Feed-forward recruitment of electrical synapses enhances synchronous spiking in the mouse cerebellar cortex. Elife 9:e57344. https://doi.org/10.7554/eLife.57344
Jelitai M, Puggioni P, Ishikawa T, Rinaldi A, Duguid I (2016) Dendritic excitation–inhibition balance shapes cerebellar output during motor behaviour. Nat Commun 7:13722. https://doi.org/10.1038/ncomms13722
Jirenhed D-A, Bengtsson F, Hesslow G (2007) Acquisition, extinction, and reacquisition of a cerebellar cortical memory trace. J Neurosci 27(10):2493–2502. https://doi.org/10.1523/JNEUROSCI.4202-06.2007
Jörntell H, Ekerot C-F (2002) Reciprocal bidirectional plasticity of parallel fiber receptive fields in cerebellar Purkinje cells and their afferent interneurons. Neuron 34(5):797–806. https://doi.org/10.1016/s0896-6273(02)00713-4
Jörntell H, Ekerot C-F (2003) Receptive field plasticity profoundly alters the cutaneous parallel fiber synaptic input to cerebellar interneurons in vivo. J Neurosci 23(29):9620–9631
Kelly L, Farrant M, Cull-Candy SG (2009) Synaptic mGluR activation drives plasticity of calcium-permeable AMPA receptors. Nat Neurosci 12(5):593–601. https://doi.org/10.1038/nn.2309
Kim J, Lee S, Tsuda S, Zhang X, Asrican B, Gloss B, Feng G, Augustine GJ (2014) Optogenetic map** of cerebellar inhibitory circuitry reveals spatially biased coordination of interneurons via electrical synapses. Cell Rep. https://doi.org/10.1016/j.celrep.2014.04.047
Kreitzer AC, Carter AG, Regehr WG (2002) Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron 34(5):787–796
Lachamp PM, Liu Y, Liu SJ (2009) Glutamatergic modulation of cerebellar interneuron activity is mediated by an enhancement of GABA release and requires protein kinase A/RIM1alpha signaling. J Neurosci 29(2):381–392. https://doi.org/10.1523/JNEUROSCI.2354-08.2009
Larson EA, Accardi MV, Wang Y, D’Antoni M, Karimi B, Siddiqui TJ, Bowie D (2020) Nitric oxide signaling strengthens inhibitory synapses of cerebellar molecular layer interneurons through a GABARAP-dependent mechanism. J Neurosci 40(17):3348. https://doi.org/10.1523/JNEUROSCI.2211-19.2020
Liu S, Cull-Candy SG (2000) Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype. Nature 405(6785):454–458. https://doi.org/10.1038/35013064
Liu SJ, Lachamp P (2006) The activation of excitatory glutamate receptors evokes a long-lasting increase in the release of GABA from cerebellar stellate cells. J Neurosci 26(36):9332–9339. https://doi.org/10.1523/JNEUROSCI.2929-06.2006
Liu Y, Formisano L, Savtchouk I, Takayasu Y, Szabó G, Zukin RS, Liu SJ (2010) A single fear-inducing stimulus induces a transcription-dependent switch in synaptic AMPAR phenotype. Nat Neurosci 13(2):223–231. https://doi.org/10.1038/nn.2474
Liu Y, Savtchouk I, Acharjee S, Liu SJ (2011) Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells. J Neurophysiol 106(1):144–152. https://doi.org/10.1152/jn.01107.2010
Llano I, Gerschenfeld HM (1993) Inhibitory synaptic currents in stellate cells of rat cerebellar slices. J Physiol 468:177–200
Mann-Metzer P, Yarom Y (1999) Electrotonic coupling interacts with intrinsic properties to generate synchronized activity in cerebellar networks of inhibitory interneurons. J Neurosci 19(9):3298–3306
McCormick DA, Thompson RF (1984) Cerebellum: essential involvement in the classically conditioned eyelid response. Science 223(4633):296–299. https://doi.org/10.1126/science.6701513
Molineux ML, Fernandez FR, Mehaffey WH, Turner RW (2005) A-type and T-type currents interact to produce a novel spike latency-voltage relationship in cerebellar stellate cells. J Neurosci 25(47):10863–10873. https://doi.org/10.1523/JNEUROSCI.3436-05.2005
Myoga MH, Beierlein M, Regehr WG (2009) Somatic spikes regulate dendritic signaling in small neurons in the absence of backpropagating action potentials. J Neurosci 29(24):7803–7814. https://doi.org/10.1523/JNEUROSCI.0030-09.2009
Rieubland S, Roth A, Häusser M (2014) Structured connectivity in cerebellar inhibitory networks. Neuron 81(4):913–929. https://doi.org/10.1016/j.neuron.2013.12.029
Rowan MJM, DelCanto G, Yu JJ, Kamasawa N, Christie JM (2016) Synapse-level determination of action potential duration by K+ channel clustering in axons. Neuron 91(2):370–383. https://doi.org/10.1016/j.neuron.2016.05.035
Sacchetti B, Baldi E, Lorenzini CA, Bucherelli C (2002) Cerebellar role in fear-conditioning consolidation. Proc Natl Acad Sci U S A 99(12):8406–8411. https://doi.org/10.1073/pnas.112660399
Sacchetti B, Scelfo B, Tempia F, Strata P (2004) Long-term synaptic changes induced in the cerebellar cortex by fear conditioning. Neuron 42(6):973–982. https://doi.org/10.1016/j.neuron.2004.05.012
Savtchouk I, Liu SJ (2011) Remodeling of synaptic AMPA receptor subtype alters the probability and pattern of action potential firing. J Neurosci 31(2):501–511. https://doi.org/10.1523/JNEUROSCI.2608-10.2011
Savtchouk I, Sun L, Bender CL, Yang Q, Szabó G, Gasparini S, Liu SJ (2016) Topological regulation of synaptic AMPA receptor expression by the RNA-binding protein CPEB3. Cell Rep 17(1):86–103. https://doi.org/10.1016/j.celrep.2016.08.094
Scelfo B, Sacchetti B, Strata P (2008) Learning-related long-term potentiation of inhibitory synapses in the cerebellar cortex. Proc Natl Acad Sci U S A 105(2):769–774. https://doi.org/10.1073/pnas.0706342105
Schmahmann JD (2010) The role of the cerebellum in cognition and emotion: personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy. Neuropsychol Rev 20(3):236–260. https://doi.org/10.1007/s11065-010-9142-x
Soler-Llavina GJ, Sabatini BL (2006) Synapse-specific plasticity and compartmentalized signaling in cerebellar stellate cells. Nat Neurosci 9(6):798–806. https://doi.org/10.1038/nn1698
Sun L, Liu SJ (2007) Activation of extrasynaptic NMDA receptors induces a PKC-dependent switch in AMPA receptor subtypes in mouse cerebellar stellate cells. J Physiol 583(Pt 2):537–553. https://doi.org/10.1113/jphysiol.2007.136788
Szapiro G, Barbour B (2007) Multiple climbing fibers signal to molecular layer interneurons exclusively via glutamate spillover. Nat Neurosci 10(6):735–742. https://doi.org/10.1038/nn1907
Tan YP, Llano I (1999) Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons. J Physiol 520(Pt 1):65–78. https://doi.org/10.1111/j.1469-7793.1999.00065.x
ten Brinke MM, Boele H-J, Spanke JK, Potters J-W, Kornysheva K, Wulff P, IJpelaar ACHG, Koekkoek SKE, De Zeeuw CI (2015) Evolving models of Pavlovian conditioning: cerebellar cortical dynamics in awake behaving mice. Cell Rep 13(9):1977–1988. https://doi.org/10.1016/j.celrep.2015.10.057
Walter JT, Alviña K, Womack MD, Chevez C, Khodakhah K (2006) Decreases in the precision of Purkinje cell pacemaking cause cerebellar dysfunction and ataxia. Nat Neurosci 9(3):389–397. https://doi.org/10.1038/nn1648
Witter L, Rudolph S, Pressler RT, Lahlaf SI, Regehr WG (2016) Purkinje cell collaterals enable output signals from the cerebellar cortex to feed back to Purkinje cells and interneurons. Neuron 91(2):312–319. https://doi.org/10.1016/j.neuron.2016.05.037
Wulff P, Goetz T, Leppä E, Linden A-M, Renzi M, Swinny JD, Vekovischeva OY, Sieghart W, Somogyi P, Korpi ER, Farrant M, Wisden W (2007) From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Nat Neurosci 10(7):923–929. https://doi.org/10.1038/nn1927
Wulff P, Schonewille M, Renzi M, Viltono L, Sassoè-Pognetto M, Badura A, Gao Z, Hoebeek FE, van Dorp S, Wisden W, Farrant M, De Zeeuw CI (2009) Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning. Nat Neurosci 12(8):1042–1049. https://doi.org/10.1038/nn.2348
Yoshida T, Hashimoto K, Zimmer A, Maejima T, Araishi K, Kano M (2002) The cannabinoid CB1 receptor mediates retrograde signals for depolarization-induced suppression of inhibition in cerebellar Purkinje cells. J Neurosci 22(5):1690–1697
Zhang B, Südhof TC (2016) Neuroligins are selectively essential for NMDAR signaling in cerebellar stellate interneurons. J Neurosci 36(35):9070. https://doi.org/10.1523/JNEUROSCI.1356-16.2016
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Liu, S.J., Dubois, C.J. (2023). Stellate Cells . In: Gruol, D.L., Koibuchi, N., Manto, M., Molinari, M., Schmahmann, J.D., Shen, Y. (eds) Essentials of Cerebellum and Cerebellar Disorders. Springer, Cham. https://doi.org/10.1007/978-3-031-15070-8_23
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