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
Learning and memory mechanisms in neural circuits
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)
Giorgio Grasselli (Postdoc)
Claire Piochon (Postdoc)
Lorenzo Rinaldo (MD/PhD Student)
Heather Titley (Postdoc)
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.
Piochon C, Kruskal P, MacLean J, and Hansel C (2013). Non-Hebbian spike-timing-dependent plasticity in cerebellar circuits. Front. Neural Circuits 6, 124.
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.
Buttermore ED, Piochon C, Wallace M, Philpot B, Hansel C, and Bhat MA (2012). Pinceau organization in the cerebellum requires distinct functions of neurofascin in Purkinje and basket neurons during postnatal development. J. Neurosci. 32, 4724-4742.
Hosy E, Piochon C, Teuling E, Rinaldo L, and Hansel C (2011). SK2 channel expression and function in cerebellar Purkinje cells. J. Physiol. (Lond.) 589.14, 3433-3440.
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.
Van Woerden GM et al. (2009). bCaMKII controls the direction of plasticity at parallel fiber-Purkinje cell synapses. Nature Neurosci. 12, 823-825.
Belmeguenai A et al. (2008). Alcohol impairs long-term depression at the cerebellar parallel fiber-Purkinje cell synapse. J. Neurophysiol. 100, 3167-3174.
Han VZ, Zhang Y, Bell CC, and Hansel C (2007). Synaptic plasticity and calcium signaling in Purkinje cells of the central cerebellar lobes of mormyrid fish. J. Neurosci. 27, 13499-13512.
Van Beugen BJ, Nagaraja RY, and Hansel C (2006). Climbing fiber-evoked endocannabinoid signaling heterosynaptically suppresses presynaptic cerebellar long-term potentiation. J. Neurosci. 26, 8289-8294.
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.