title: Hyperpolarization induces a long-term increase in the spontaneous firing rate of cerebellar Golgi cells.
abstract: Golgi cells (GoCs) are inhibitory interneurons that influence the cerebellar cortical response to sensory input by regulating the excitability of the granule cell layer. While GoC inhibition is essential for normal motor coordination, little is known about the circuit dynamics that govern the activity of these cells. In particular, although GoC spontaneous spiking influences the extent of inhibition and gain throughout the granule cell layer, it is not known whether this spontaneous activity can be modulated in a long-term manner. Here we describe a form of long-term plasticity that regulates the spontaneous firing rate of GoCs in the rat cerebellar cortex. We find that membrane hyperpolarization, either by mGluR2 activation of potassium channels, or by somatic current injection, induces a long-lasting increase in GoC spontaneous firing. This spike rate plasticity appears to result from a strong reduction in the spike after hyperpolarization. Pharmacological manipulations suggest the involvement of calcium-calmodulin-dependent kinase II and calcium-activated potassium channels in mediating these firing rate increases. As a consequence of this plasticity, GoC spontaneous spiking is selectively enhanced, but the gain of evoked spiking is unaffected. Hence, this plasticity is well suited for selectively regulating the tonic output of GoCs rather than their sensory-evoked responses.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Court A
authors.initials: CA
authors.lastname: Hull
authors.forename: YunXiang
authors.initials: Y
authors.lastname: Chu
authors.forename: Monica
authors.initials: M
authors.lastname: Thanawala
authors.forename: Wade G
authors.initials: WG
authors.lastname: Regehr
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques; D010721:Phosphinic Acids / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D024681:Potassium Channels, Calcium-Activated; D011412:Propanolamines; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C085075:CGP 55845A; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
references.citation: Nature. 2009 Mar 19;458(7236):299-304
references.pmid: 19295602
references.citation: J Neurosci. 2011 Jan 12;31(2):712-24
references.pmid: 21228180
references.citation: Eur J Neurosci. 2010 Aug;32(4):591-7
references.pmid: 20718856
references.citation: J Physiol. 2006 Jul 15;574(Pt 2):491-507
references.pmid: 16709640
references.citation: PLoS One. 2009 Nov 24;4(11):e7991
references.pmid: 19956720
references.citation: Neuron. 2003 Oct 30;40(3):609-20
references.pmid: 14642283
references.citation: Neuron. 2005 May 19;46(4):623-31
references.pmid: 15944130
references.citation: Neuron. 2009 Jan 15;61(1):126-39
references.pmid: 19146818
references.citation: Neuron. 2012 Jan 12;73(1):149-58
references.pmid: 22243753
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14066-71
references.pmid: 9391153
references.citation: Nat Neurosci. 2005 Dec;8(12):1752-9
references.pmid: 16261134
references.citation: Cell. 1998 Oct 2;95(1):17-27
references.pmid: 9778244
references.citation: Nature. 1964 Dec 26;204:1265-6
references.pmid: 14254404
references.citation: J Neurosci. 2000 Dec 1;20(23):8651-8
references.pmid: 11102470
references.citation: J Neurosci. 2012 Aug 8;32(32):11132-43
references.pmid: 22875944
references.citation: J Physiol. 2006 Aug 1;574(Pt 3):711-29
references.pmid: 16690702
references.citation: J Neurophysiol. 2011 Apr;105(4):1651-9
references.pmid: 21307321
references.citation: J Physiol. 1996 Dec 15;497 ( Pt 3):753-9
references.pmid: 9003560
references.citation: Neuron. 2003 Aug 28;39(5):821-9
references.pmid: 12948448
references.citation: Nature. 2004 Apr 22;428(6985):856-60
references.pmid: 15103377
references.citation: Neuron. 2002 Feb 14;33(4):625-33
references.pmid: 11856535
references.citation: Neuron. 2009 Sep 24;63(6):843-53
references.pmid: 19778512
references.citation: Neuron. 2003 May 8;38(3):433-45
references.pmid: 12741990
references.citation: Neuron. 2010 Aug 12;67(3):435-51
references.pmid: 20696381
references.citation: Neuron. 2008 Oct 23;60(2):343-52
references.pmid: 18957225
references.citation: Neuron. 1994 Jul;13(1):55-66
references.pmid: 8043281
references.citation: Prog Neurobiol. 2006 Feb-Apr;78(3-5):272-303
references.pmid: 16759785
references.citation: J Neurophysiol. 2005 Jan;93(1):467-80
references.pmid: 15317837