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Christian R. Hansel

InstitutionUniversity of Chicago
AddressChicago IL 60637
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    Neural networks are able to store information and to learn by adapting the efficacy of synaptic communication between neurons in an activity-dependent way. ‘Synaptic memory’ formation can be bidirectional: synapses can undergo long-term potentiation (LTP) or long-term depression (LTD). These processes participate in behavioral learning in specific ways that depend on the layout of the neuronal circuit that is studied.

    In our laboratory, we examine forms of synaptic and non-synaptic plasticity in the cerebellum, a brain area that is involved in fine adaptation of movements, but is involved in cognitive functions as well. In Marr-Albus-Ito models of cerebellar function, LTD at parallel fiber (PF) synapses onto Purkinje cells, which provide the sole output of the cerebellar cortex, is seen as a cellular correlate of motor learning, and forms of associative learning in general. LTD is induced by co-activation of PF synapses with the climbing fiber (CF) input, and is postsynaptically induced and expressed. Next to LTD, we also study a postsynaptic form of LTP at PF synapses that is induced by isolated PF activation and might provide a reversal mechanism for LTD (formally, LTD might also provide a reversal mechanism for LTP). We have recently shown that bidirectional plasticity at PF synapses is governed by induction rules that operate inverse to their counterparts at hippocampal and neocortical synapses: 1) PF-LTD needs larger calcium transients for its induction than LTP, and 2) PF-LTD is kinase-dependent (PKC / aCaMKII), whereas PF-LTP is phosphatase-dependent. Moreover, we have shown that the direction of synaptic gain change (potentiation or depression) depends on whether the CF input was co-activated (LTD) or not (LTP). This control by a qualitatively different heterosynaptic input provides a unique plasticity motif in the brain. In addition to LTD and LTP, we also examine intrinsic plasticity in Purkinje cells. We have shown that the intrinsic excitability of Purkinje cells can be amplified by a downregulation of calcium-dependent SK2-type potassium channels, and that this form of plasticity complements LTD and LTP in information storage.

    In the lab, we use patch-clamp recording techniques (incl. patch-clamp recordings from Purkinje cell dendrites), as well as confocal calcium imaging to study the cellular and molecular mechanisms underlying learning and memory. These studies are complemented by the use of additional techniques such as immunohistochemistry and behavioral testing. More recently, we also study the effects of alcohol on cerebellar function and motor adaptation, and the role of deficits in cerebellar associative learning in autism spectrum disorder (ASD).

    Collapse Biography 
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    University of Zurich, SwitzerlandDiplomaZoology
    Max-Planck-Institute for Brain Research, Frankfurt, GermanyPh.D.Neurobiology
    Johns Hopkins University, BaltimorePostdocNeurobiology

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Hansel C. Contiguity in perception: origins in cellular associative computations. Trends Neurosci. 2024 03; 47(3):170-180. PMID: 38310022; PMCID: PMC10939850.
      Citations:    Fields:    Translation:Humans
    2. Lin TF, Busch SE, Hansel C. Intrinsic and synaptic determinants of receptive field plasticity in Purkinje cells of the mouse cerebellum. bioRxiv. 2023 Aug 19. PMID: 37502848; PMCID: PMC10370111.
    3. Busch SE, Hansel C. Climbing fiber multi-innervation of mouse Purkinje dendrites with arborization common to human. Science. 2023 07 28; 381(6656):420-427. PMID: 37499000; PMCID: PMC10962609.
      Citations: 3     Fields:    Translation:HumansAnimalsCells
    4. Busch SE, Simmons DH, Gama E, Du X, Longo F, Gomez CM, Klann E, Hansel C. Overexpression of the autism candidate gene Cyfip1 pathologically enhances olivo-cerebellar signaling in mice. Front Cell Neurosci. 2023; 17:1219270. PMID: 37545882; PMCID: PMC10399232.
      Citations: 1     
    5. Yang R, Feng X, Arias-Cavieres A, Mitchell RM, Polo A, Hu K, Zhong R, Qi C, Zhang RS, Westneat N, Portillo CA, Nobrega MA, Hansel C, Garcia Iii AJ, Zhang X. Upregulation of SYNGAP1 expression in mice and human neurons by redirecting alternative splicing. Neuron. 2023 05 17; 111(10):1637-1650.e5. PMID: 36917980; PMCID: PMC10198817.
      Citations: 7     Fields:    Translation:HumansAnimalsCells
    6. Pham T, Hansel C. Intrinsic threshold plasticity: cholinergic activation and role in the neuronal recognition of incomplete input patterns. J Physiol. 2023 08; 601(15):3221-3239. PMID: 35879872; PMCID: PMC9873838.
      Citations:    Fields:    Translation:AnimalsCells
    7. Piochon C, Titley HK, Hansel C, Levenes C. The calcium sensor, rather than the route of calcium entry, defines cerebellar plasticity pathways. Proc Natl Acad Sci U S A. 2022 02 22; 119(8). PMID: 35193964; PMCID: PMC8872713.
      Citations: 3     Fields:    
    8. Simmons DH, Busch SE, Titley HK, Grasselli G, Shih J, Du X, Wei C, Gomez CM, Piochon C, Hansel C. Sensory Over-responsivity and Aberrant Plasticity in Cerebellar Cortex in a Mouse Model of Syndromic Autism. Biol Psychiatry Glob Open Sci. 2022 Oct; 2(4):450-459. PMID: 36324646; PMCID: PMC9616247.
      Citations: 2     
    9. Hansel C. Part II. J. C. Eccles, R. Llinas and K. Sasaki, The Excitatory Synaptic Action of Climbing Fibres on the Purkinje Cells of the Cerebellum, J Physiol, 182: 268-296, 1966: the Rise of the Complex Spike. Cerebellum. 2021 06; 20(3):330-339. PMID: 33638794.
      Citations: 1     Fields:    Translation:HumansAnimalsCells
    10. Hansel C, Disterhoft JF. Why is synaptic plasticity not enough? Neurobiol Learn Mem. 2020 12; 176:107336. PMID: 33137462.
      Citations: 3     Fields:    Translation:AnimalsCells
    11. Simmons DH, Titley HK, Hansel C, Mason P. Behavioral Tests for Mouse Models of Autism: An Argument for the Inclusion of Cerebellum-Controlled Motor Behaviors. Neuroscience. 2021 05 10; 462:303-319. PMID: 32417339.
      Citations: 19     Fields:    Translation:HumansAnimals
    12. Gill DF, Hansel C. Muscarinic Modulation of SK2-Type K+ Channels Promotes Intrinsic Plasticity in L2/3 Pyramidal Neurons of the Mouse Primary Somatosensory Cortex. eNeuro. 2020 Mar/Apr; 7(2). PMID: 32005752; PMCID: PMC7294454.
      Citations: 7     Fields:    Translation:AnimalsCells
    13. Titley HK, Watkins GV, Lin C, Weiss C, McCarthy M, Disterhoft JF, Hansel C. Intrinsic Excitability Increase in Cerebellar Purkinje Cells after Delay Eye-Blink Conditioning in Mice. J Neurosci. 2020 03 04; 40(10):2038-2046. PMID: 32015022; PMCID: PMC7055141.
      Citations: 18     Fields:    Translation:AnimalsCells
    14. Grasselli G, Boele HJ, Titley HK, Bradford N, van Beers L, Jay L, Beekhof GC, Busch SE, De Zeeuw CI, Schonewille M, Hansel C. SK2 channels in cerebellar Purkinje cells contribute to excitability modulation in motor-learning-specific memory traces. PLoS Biol. 2020 01; 18(1):e3000596. PMID: 31905212; PMCID: PMC6964916.
      Citations: 28     Fields:    Translation:AnimalsCells
    15. Titley HK, Kislin M, Simmons DH, Wang SS, Hansel C. Complex spike clusters and false-positive rejection in a cerebellar supervised learning rule. J Physiol. 2019 08; 597(16):4387-4406. PMID: 31297821; PMCID: PMC6697200.
      Citations: 15     Fields:    Translation:AnimalsCells
    16. Du X, Wei C, Hejazi Pastor DP, Rao ER, Li Y, Grasselli G, Godfrey J, Palmenberg AC, Andrade J, Hansel C, Gomez CM. a1ACT Is Essential for Survival and Early Cerebellar Programming in a Critical Neonatal Window. Neuron. 2019 05 22; 102(4):770-785.e7. PMID: 30922876; PMCID: PMC6533132.
      Citations: 13     Fields:    Translation:HumansAnimalsCells
    17. Ohtsuki G, Hansel C. Synaptic Potential and Plasticity of an SK2 Channel Gate Regulate Spike Burst Activity in Cerebellar Purkinje Cells. iScience. 2018 Mar 23; 1:49-54. PMID: 29888747; PMCID: PMC5993052.
      Citations: 14     
    18. Hansel C. Deregulation of synaptic plasticity in autism. Neurosci Lett. 2019 01 01; 688:58-61. PMID: 29421544.
      Citations: 31     Fields:    Translation:HumansAnimals
    19. Titley HK, Brunel N, Hansel C. Toward a Neurocentric View of Learning. Neuron. 2017 Jul 05; 95(1):19-32. PMID: 28683265; PMCID: PMC5519140.
      Citations: 92     Fields:    Translation:AnimalsCells
    20. Piochon C, Titley HK, Simmons DH, Grasselli G, Elgersma Y, Hansel C. Calcium threshold shift enables frequency-independent control of plasticity by an instructive signal. Proc Natl Acad Sci U S A. 2016 11 15; 113(46):13221-13226. PMID: 27799554; PMCID: PMC5135319.
      Citations: 24     Fields:    Translation:AnimalsCells
    21. Piochon C, Kano M, Hansel C. LTD-like molecular pathways in developmental synaptic pruning. Nat Neurosci. 2016 09 27; 19(10):1299-310. PMID: 27669991; PMCID: PMC5070480.
      Citations: 41     Fields:    Translation:HumansAnimals
    22. Titley HK, Hansel C. Asymmetries in Cerebellar Plasticity and Motor Learning. Cerebellum. 2016 Apr; 15(2):87-92. PMID: 25578035; PMCID: PMC4500681.
      Citations: 7     Fields:    Translation:HumansAnimalsCells
    23. Grasselli G, He Q, Wan V, Adelman JP, Ohtsuki G, Hansel C. Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells. Cell Rep. 2016 Mar 22; 14(11):2546-53. PMID: 26972012; PMCID: PMC4805497.
      Citations: 31     Fields:    Translation:AnimalsCells
    24. Kloth AD, Badura A, Li A, Cherskov A, Connolly SG, Giovannucci A, Bangash MA, Grasselli G, Piochon C, Tsai PT, Geschwind DH, Hansel C, Sahin M, Takumi T, Worley PF, Wang SS, Peñagarikano O. Cerebellar associative sensory learning defects in five mouse autism models. Elife. 2015 Jul 09; 4:e06085. PMID: 26158416; PMCID: PMC4512177.
      Citations: 66     Fields:    Translation:AnimalsCells
    25. Shih EK, Ohtsuki G, Aldinger KA, Chizhikov VV, Hansel C, Mugnaini E, Millen KJ, Sekerková G. The Spontaneous Ataxic Mouse Mutant Tippy is Characterized by a Novel Purkinje Cell Morphogenesis and Degeneration Phenotype. Cerebellum. 2015 Jun; 14(3):292-307. PMID: 25626522; PMCID: PMC4832921.
      Citations: 6     Fields:    Translation:AnimalsCells
    26. Piochon C, Kloth AD, Grasselli G, Titley HK, Nakayama H, Hashimoto K, Wan V, Simmons DH, Eissa T, Nakatani J, Cherskov A, Miyazaki T, Watanabe M, Takumi T, Kano M, Wang SS, Hansel C. Corrigendum: Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism. Nat Commun. 2015 Jan 27; 6:6014. PMID: 25625889.
      Citations: 3     Fields:    
    27. Piochon C, Kloth AD, Grasselli G, Titley HK, Nakayama H, Hashimoto K, Wan V, Simmons DH, Eissa T, Nakatani J, Cherskov A, Miyazaki T, Watanabe M, Takumi T, Kano M, Wang SS, Hansel C. Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism. Nat Commun. 2014 Nov 24; 5:5586. PMID: 25418414; PMCID: PMC4243533.
      Citations: 80     Fields:    Translation:AnimalsCells
    28. van Beugen BJ, Qiao X, Simmons DH, De Zeeuw CI, Hansel C. Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation. Learn Mem. 2014 Dec; 21(12):662-7. PMID: 25403454; PMCID: PMC4236409.
      Citations: 7     Fields:    Translation:AnimalsCells
    29. Grasselli G, Hansel C. Cerebellar long-term potentiation: cellular mechanisms and role in learning. Int Rev Neurobiol. 2014; 117:39-51. PMID: 25172628.
      Citations: 22     Fields:    Translation:HumansAnimalsCells
    30. Du X, Wang J, Zhu H, Rinaldo L, Lamar KM, Palmenberg AC, Hansel C, Gomez CM. Second cistron in CACNA1A gene encodes a transcription factor mediating cerebellar development and SCA6. Cell. 2013 Jul 03; 154(1):118-33. PMID: 23827678; PMCID: PMC3939801.
      Citations: 86     Fields:    Translation:HumansAnimalsCells
    31. Rinaldo L, Hansel C. Muscarinic acetylcholine receptor activation blocks long-term potentiation at cerebellar parallel fiber-Purkinje cell synapses via cannabinoid signaling. Proc Natl Acad Sci U S A. 2013 Jul 02; 110(27):11181-6. PMID: 23776234; PMCID: PMC3704018.
      Citations: 18     Fields:    Translation:AnimalsCells
    32. Piochon C, Kruskal P, Maclean J, Hansel C. Non-Hebbian spike-timing-dependent plasticity in cerebellar circuits. Front Neural Circuits. 2012; 6:124. PMID: 23335888; PMCID: PMC3542521.
      Citations: 17     Fields:    
    33. He Q, Titley H, Grasselli G, Piochon C, Hansel C. Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD. J Neurophysiol. 2013 Mar; 109(5):1333-42. PMID: 23221414; PMCID: PMC3602830.
      Citations: 23     Fields:    Translation:AnimalsCells
    34. Ohtsuki G, Piochon C, Adelman JP, Hansel C. SK2 channel modulation contributes to compartment-specific dendritic plasticity in cerebellar Purkinje cells. Neuron. 2012 Jul 12; 75(1):108-20. PMID: 22794265; PMCID: PMC3398406.
      Citations: 57     Fields:    Translation:AnimalsCells
    35. Buttermore ED, Piochon C, Wallace ML, Philpot BD, Hansel C, Bhat MA. Pinceau organization in the cerebellum requires distinct functions of neurofascin in Purkinje and basket neurons during postnatal development. J Neurosci. 2012 Apr 04; 32(14):4724-42. PMID: 22492029; PMCID: PMC3337041.
      Citations: 34     Fields:    Translation:AnimalsCells
    36. Hosy E, Piochon C, Teuling E, Rinaldo L, Hansel C. SK2 channel expression and function in cerebellar Purkinje cells. J Physiol. 2011 Jul 15; 589(Pt 14):3433-40. PMID: 21521760; PMCID: PMC3167108.
      Citations: 35     Fields:    Translation:AnimalsCells
    37. Piochon C, Levenes C, Ohtsuki G, Hansel C. Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum. J Neurosci. 2010 Nov 10; 30(45):15330-5. PMID: 21068337; PMCID: PMC2990192.
      Citations: 54     Fields:    Translation:AnimalsCells
    38. Belmeguenai A, Hosy E, Bengtsson F, Pedroarena CM, Piochon C, Teuling E, He Q, Ohtsuki G, De Jeu MT, Elgersma Y, De Zeeuw CI, Hansel C, Jörntell H. Intrinsic plasticity complements long-term potentiation in parallel fiber input gain control in cerebellar Purkinje cells. J Neurosci. 2010 Oct 13; 30(41):13630-43. PMID: 20943904; PMCID: PMC2968711.
      Citations: 78     Fields:    Translation:AnimalsCells
    39. Rinaldo L, Hansel C. Ataxias and cerebellar dysfunction: involvement of synaptic plasticity deficits? Funct Neurol. 2010 Jul-Sep; 25(3):135-9. PMID: 21232209; PMCID: PMC3056151.
      Citations: 16     Fields:    Translation:HumansAnimalsCells
    40. Ohtsuki G, Piochon C, Hansel C. Climbing fiber signaling and cerebellar gain control. Front Cell Neurosci. 2009; 3:4. PMID: 19597563; PMCID: PMC2708967.
      Citations: 32     
    41. van Woerden GM, Hoebeek FE, Gao Z, Nagaraja RY, Hoogenraad CC, Kushner SA, Hansel C, De Zeeuw CI, Elgersma Y. betaCaMKII controls the direction of plasticity at parallel fiber-Purkinje cell synapses. Nat Neurosci. 2009 Jul; 12(7):823-5. PMID: 19503086.
      Citations: 65     Fields:    Translation:AnimalsCells
    42. Hansel C. Reading the clock: how Purkinje cells decode the phase of olivary oscillations. Neuron. 2009 May 14; 62(3):308-9. PMID: 19447086.
      Citations: 7     Fields:    Translation:AnimalsCells
    43. Belmeguenai A, Botta P, Weber JT, Carta M, De Ruiter M, De Zeeuw CI, Valenzuela CF, Hansel C. Alcohol impairs long-term depression at the cerebellar parallel fiber-Purkinje cell synapse. J Neurophysiol. 2008 Dec; 100(6):3167-74. PMID: 18922952; PMCID: PMC2604851.
      Citations: 40     Fields:    Translation:AnimalsCells
    44. Han VZ, Zhang Y, Bell CC, Hansel C. Synaptic plasticity and calcium signaling in Purkinje cells of the central cerebellar lobes of mormyrid fish. J Neurosci. 2007 Dec 05; 27(49):13499-512. PMID: 18057208; PMCID: PMC6673090.
      Citations: 19     Fields:    Translation:AnimalsCells
    45. Yuan Q, Qiu DL, Weber JT, Hansel C, Knöpfel T. Climbing fiber-triggered metabotropic slow potentials enhance dendritic calcium transients and simple spike firing in cerebellar Purkinje cells. Mol Cell Neurosci. 2007 Aug; 35(4):596-603. PMID: 17604180.
      Citations: 10     Fields:    Translation:AnimalsCells
    46. Hansel C, Jörntell H. Synaptic memories upside down: bidirectional plasticity at cerebellar parallel fiber-Purkinje cell synapses. Neuron. 2006 Oct 19; 52(2):227-38. PMID: 17046686.
      Citations: 169     Fields:    Translation:HumansAnimalsCells
    47. Hansel C, de Jeu M, Belmeguenai A, Houtman SH, Andreev D, De Zeeuw CI, Elgersma Y, Buitendijk GH. alphaCaMKII Is essential for cerebellar LTD and motor learning. Neuron. 2006 Sep 21; 51(6):835-43. PMID: 16982427.
      Citations: 118     Fields:    Translation:AnimalsCells
    48. van Beugen BJ, Nagaraja RY, Hansel C. Climbing fiber-evoked endocannabinoid signaling heterosynaptically suppresses presynaptic cerebellar long-term potentiation. J Neurosci. 2006 Aug 09; 26(32):8289-94. PMID: 16899723; PMCID: PMC6673796.
      Citations: 23     Fields:    Translation:AnimalsCells
    49. de Ruiter MM, De Zeeuw CI, Hansel C. Voltage-gated sodium channels in cerebellar Purkinje cells of mormyrid fish. J Neurophysiol. 2006 Jul; 96(1):378-90. PMID: 16598064.
      Citations: 10     Fields:    Translation:AnimalsCells
    50. Hansel C. When the B-team runs plasticity: GluR2 receptor trafficking in cerebellar long-term potentiation. Proc Natl Acad Sci U S A. 2005 Dec 20; 102(51):18245-6. PMID: 16344457; PMCID: PMC1317989.
      Citations: 5     Fields:    
    51. Belmeguenai A, Hansel C. A role for protein phosphatases 1, 2A, and 2B in cerebellar long-term potentiation. J Neurosci. 2005 Nov 16; 25(46):10768-72. PMID: 16291950; PMCID: PMC6725852.
      Citations: 77     Fields:    Translation:Animals
    52. Schmolesky MT, De Zeeuw CI, Hansel C. Climbing fiber synaptic plasticity and modifications in Purkinje cell excitability. Prog Brain Res. 2005; 148:81-94. PMID: 15661183.
      Citations: 7     Fields:    Translation:HumansAnimalsCells
    53. Coesmans M, Weber JT, De Zeeuw CI, Hansel C. Bidirectional parallel fiber plasticity in the cerebellum under climbing fiber control. Neuron. 2004 Nov 18; 44(4):691-700. PMID: 15541316.
      Citations: 198     Fields:    Translation:AnimalsCells
    54. Weber JT, De Zeeuw CI, Linden DJ, Hansel C. Long-term depression of climbing fiber-evoked calcium transients in Purkinje cell dendrites. Proc Natl Acad Sci U S A. 2003 Mar 04; 100(5):2878-83. PMID: 12601151; PMCID: PMC151434.
      Citations: 29     Fields:    Translation:AnimalsCells
    55. Schmolesky MT, Weber JT, De Zeeuw CI, Hansel C. The making of a complex spike: ionic composition and plasticity. Ann N Y Acad Sci. 2002 Dec; 978:359-90. PMID: 12582067.
      Citations: 74     Fields:    Translation:HumansAnimalsCells
    56. Shen Y, Hansel C, Linden DJ. Glutamate release during LTD at cerebellar climbing fiber-Purkinje cell synapses. Nat Neurosci. 2002 Aug; 5(8):725-6. PMID: 12134155.
      Citations: 14     Fields:    Translation:AnimalsCells
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