Christian Hansel


Department of Neurobiology

The University of Chicago
947 E. 58th St., MC0928
Chicago, IL 60637 

Phone: (773) 702-1555
Fax: (773) 702-1216

Hansel lab website


Research Summary

Learning and memory mechanisms in neural circuits


Research Statement

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).

The Hansel lab:

Christian Hansel (Principal Investigator)

Daniel Gill (PhD Student)

Giorgio Grasselli (Postdoc)

Dana Simmons (PhD Student)

Heather Titley (Postdoc)

Gabrielle Watkins (PhD Student)


Select Publications

Piochon C et al. (2016). Calcium threshold shift enables frequency-independent control of plasticity by an instructive signal. Proc. Natl. Acad. Sci. USA 113, 13221-13226.

Piochon C, Kano M, and Hansel C (2016). LTD-like molecular pathways in developmental synaptic pruning. Nature Neurosci. 19, 1299-1310.

Grasselli G et al. (2016). Activity-dependent plasticity of spike pauses in cerebellar Purkinje cells. Cell Reports 14, 2546-2553.

Kloth AD et al. (2015). Cerebellar associative sensory learning defects in five mouse autism models. eLife 4, e06085.

Piochon C et al. (2014). Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism. Nature Commun. 5, 5586.

Van Beugen BJ, Qiao X, Simmons DH, De Zeeuw CI, and Hansel C (2014). Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation. Learn. Mem. 21, 662-667.

Rinaldo L and Hansel C (2013). Muscarinic acetylcholine receptor activation blocks long-term potentiation at cerebellar parallel fiber-Purkinje cell synapses via cannabinoid signaling. Proc. Natl. Acad. Sci. USA 110, 11181-11186.

Du X et al (2013). Second cistron in CACNA1A gene encodes a transcription factor mediating cerebellar development and SCA6. Cell 154, 118-133.

He Q, Titley H, Grasselli G, Piochon C, and Hansel C (2013). Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD. J. Neurophysiol. 109, 1333-1342.

Ohtsuki G, Piochon C, Adelman JP, and Hansel C (2012). SK2 channel modulation contributes to compartment-specific dendritic plasticity in cerebellar Purkinje cells. Neuron 75, 108-120.

Piochon C, Levenes C, Ohtsuki G, and Hansel C (2010). Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum. J. Neurosci. 30, 15330-15335.

Belmeguenai A et al (2010). Intrinsic plasticity complements LTP in parallel fiber input gain control in cerebellar Purkinje cells. J. Neurosci. 30, 13630-13643.

Schonewille M et al (2010). Purkinje cell-specific knockout of the protein phosphatase PP2B impairs potentiation and cerebellar motor learning. Neuron 67, 618-628.

Jorntell H and Hansel C (2006). Synaptic memories upside down: bidirectional plasticity at cerebellar parallel fiber-Purkinje cell synapses. Neuron 52, 227-238.

Hansel C et al. (2006). aCaMKII is essential for cerebellar LTD and motor learning. Neuron 51, 835-843.

Coesmans M, Weber JT, De Zeeuw CI, and Hansel C (2004). Bidirectional parallel fiber plasticity in the cerebellum under climbing fiber control. Neuron 44, 691-700.

Hansel C, Linden DJ, and D'Angelo E (2001). Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum. Nature Neurosci. 4, 467-475.