TY - JOUR
T1 - Intrinsic excitability increase in cerebellar Purkinje cells after delay eye-blink conditioning in mice
AU - Titley, Heather K.
AU - Watkins, Gabrielle V.
AU - Lin, Carmen
AU - Weiss, Craig
AU - McCarthy, Michael
AU - Disterhoft, John F.
AU - Hansel, Christian
N1 - Funding Information:
This work was supported by the National Institutes of Health (National Institute of Neurological Disorders and Stroke Grant NS-062271 to C.H. and J.F.D. and National Institute on Aging Grant R37 AG008796 to J.F.D.). We like to thank members of the Hansel and Disterhoft laboratories for many helpful discussions.
Funding Information:
Received Sept. 18, 2019; revised Dec. 2, 2019; accepted Dec. 4, 2019. Authorcontributions:H.K.T.,G.V.W.,C.W.,J.F.D.,andC.H.designedresearch;H.K.T.,G.V.W.,C.L.,C.W.,andM.M. performed research; H.K.T., G.V.W., C.L., C.W., and M.M. analyzed data; H.K.T., G.V.W., C.W., J.F.D., and C.H. edited the paper; J.F.D. and C.H. wrote the paper; C.H. wrote the first draft of the paper. This work was supported by the National Institutes of Health (National Institute of Neurological Disorders and StrokeGrantNS-062271toC.H.andJ.F.D.andNationalInstituteonAgingGrantR37AG008796toJ.F.D.).Weliketo thank members of the Hansel and Disterhoft laboratories for many helpful discussions. The authors declare no competing financial interests. *H.K.T. and G.V.W. contributed equally to this work. Correspondence should be addressed to Christian Hansel at chansel@bsd.uchicago.edu.
Publisher Copyright:
© Copyright © 2020 the authors
PY - 2020/3/4
Y1 - 2020/3/4
N2 - Cerebellar-based learning is thought to rely on synaptic plasticity, particularly at synaptic inputs to Purkinje cells. Recently, however, other complementary mechanisms have been identified. Intrinsic plasticity is one such mechanism, and depends in part on the downregulation of calcium-dependent SK-type K + channels, which contribute to a medium-slow afterhyperpolarization (AHP) after spike bursts, regulating membrane excitability. In the hippocampus, intrinsic plasticity plays a role in trace eye-blink conditioning; however, corresponding excitability changes in the cerebellum in associative learning, such as in trace or delay eye-blink conditioning, are less well studied. Whole-cell patch-clamp recordings were obtained from Purkinje cells in cerebellar slices prepared from male mice ~48 h after they learned a delay eye-blink conditioning task. Over a period of repeated training sessions, mice received either paired trials of a tone coterminating with a periorbital shock (conditioning) or trials in which these stimuli were randomly presented in an unpaired manner (pseudoconditioning). Purkinje cells from conditioned mice show a significantly reduced AHP after trains of parallel fiber stimuli and after climbing fiber evoked complex spikes. The number of spikelets in the complex spike waveform is increased after conditioning. Moreover, we find that SK-dependent intrinsic plasticity is occluded in conditioned, but not pseudoconditioned mice. These findings show that excitability is enhanced in Purkinje cells after delay eye-blink conditioning, and point toward a downregulation of SK channels as a potential underlying mechanism. The observation that this learning effect lasts at least up to 2 d after training shows that intrinsic plasticity regulates excitability in the long term.
AB - Cerebellar-based learning is thought to rely on synaptic plasticity, particularly at synaptic inputs to Purkinje cells. Recently, however, other complementary mechanisms have been identified. Intrinsic plasticity is one such mechanism, and depends in part on the downregulation of calcium-dependent SK-type K + channels, which contribute to a medium-slow afterhyperpolarization (AHP) after spike bursts, regulating membrane excitability. In the hippocampus, intrinsic plasticity plays a role in trace eye-blink conditioning; however, corresponding excitability changes in the cerebellum in associative learning, such as in trace or delay eye-blink conditioning, are less well studied. Whole-cell patch-clamp recordings were obtained from Purkinje cells in cerebellar slices prepared from male mice ~48 h after they learned a delay eye-blink conditioning task. Over a period of repeated training sessions, mice received either paired trials of a tone coterminating with a periorbital shock (conditioning) or trials in which these stimuli were randomly presented in an unpaired manner (pseudoconditioning). Purkinje cells from conditioned mice show a significantly reduced AHP after trains of parallel fiber stimuli and after climbing fiber evoked complex spikes. The number of spikelets in the complex spike waveform is increased after conditioning. Moreover, we find that SK-dependent intrinsic plasticity is occluded in conditioned, but not pseudoconditioned mice. These findings show that excitability is enhanced in Purkinje cells after delay eye-blink conditioning, and point toward a downregulation of SK channels as a potential underlying mechanism. The observation that this learning effect lasts at least up to 2 d after training shows that intrinsic plasticity regulates excitability in the long term.
KW - Cerebellum
KW - Engram
KW - Learning
KW - Memory
KW - Neuron
KW - Plasticity
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UR - http://www.scopus.com/inward/citedby.url?scp=85078927669&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2259-19.2019
DO - 10.1523/JNEUROSCI.2259-19.2019
M3 - Article
C2 - 32015022
AN - SCOPUS:85078927669
VL - 40
SP - 2038
EP - 2046
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 10
ER -