Christian R. Hansel, PhD

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).

University of Zurich
Switzerland
Diploma - Zoology

Max-Planck-Institute for Brain Research
Frankfurt, Germany
Ph.D. - Neurobiology

Johns Hopkins University
Baltimore
Postdoc - Neurobiology

Why is synaptic plasticity not enough?
Hansel C, Disterhoft JF. Why is synaptic plasticity not enough? Neurobiol Learn Mem. 2020 Dec; 176:107336.
PMID: 33137462

Behavioral Tests for Mouse Models of Autism: An Argument for the Inclusion of Cerebellum-Controlled Motor Behaviors.
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. 2020 May 15.
PMID: 32417339

Muscarinic Modulation of SK2-Type K+ Channels Promotes Intrinsic Plasticity in L2/3 Pyramidal Neurons of the Mouse Primary Somatosensory Cortex.
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

Intrinsic Excitability Increase in Cerebellar Purkinje Cells after Delay Eye-Blink Conditioning in Mice.
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

SK2 channels in cerebellar Purkinje cells contribute to excitability modulation in motor-learning-specific memory traces.
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

Complex spike clusters and false-positive rejection in a cerebellar supervised learning rule.
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

a1ACT Is Essential for Survival and Early Cerebellar Programming in a Critical Neonatal Window.
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

Synaptic Potential and Plasticity of an SK2 Channel Gate Regulate Spike Burst Activity in Cerebellar Purkinje Cells.
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

Deregulation of synaptic plasticity in autism.
Hansel C. Deregulation of synaptic plasticity in autism. Neurosci Lett. 2019 01 01; 688:58-61.
PMID: 29421544

Toward a Neurocentric View of Learning.
Titley HK, Brunel N, Hansel C. Toward a Neurocentric View of Learning. Neuron. 2017 Jul 05; 95(1):19-32.
PMID: 28683265

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