# Intrinsic Plasticity and Information Storage in Cerebellar Purkinje Cells

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $474,472

## Abstract

Project Summary:
 Associative learning rests on the strengthening of synaptic inputs that show coincident activity over
extended periods of time. A notable exception is provided by supervised associative learning in the cerebellum.
Parallel fiber (PF) - Purkinje cell synapses, whose activity predicts a climbing fiber (CF)-mediated error signal,
undergo long-term depression (LTD). Since Purkinje cells are inhibitory neurons, classic Marr-Albus-Ito
theories of cerebellar function state that LTD at glutamatergic PF inputs causes disinhibition of target cells in
the cerebellar nuclei, thus enabling motor learning. However, more recent evidence challenges the notion of
LTD as the only, or the predominant, cellular mechanism underlying associative motor learning. For example,
findings from our laboratory show that in mice Purkinje cell excitability is enhanced after eyeblink conditioning
(delay EBC), and that mice with a Purkinje cell-specific knockout of SK2-type K+ channels show reduced EBC.
SK2 channels are small conductance, calcium-dependent K+ channels that are downregulated in a form of
non-synaptic (‘intrinsic’) plasticity, which enhances Purkinje cell excitability. Intrinsic plasticity is co-induced
with long-term potentiation (LTP) at PF synapses. A scenario emerges, in which an intrinsic plasticity-assisted
potentiation of those PF inputs that warn of an upcoming error signal (without contributing to it) enables EBC
learning, possibly in parallel with depression at other PF synapses, whose activity continues to predict the error
signal throughout learning. This scenario is in line with an adaptive filter model of cerebellar learning, in which
bidirectional synaptic weight adjustment under supervision of a teacher signal is crucial for the fine-tuning of
motor output. Here, we plan to use two-photon measurements of GCaMP6f-encoded, dendritic calcium signals
in Purkinje cells of awake mice to test the hypothesis that during EBC the dendritic input map is restructuring.
We predict that this map plasticity does not only consist of depression of response amplitudes at some PF
synapses, but also the emergence of responses at other PF inputs, whose activity shifts from predicting the
unconditioned stimulus (US; periorbital airpuff) to predicting the occurrence of the developing eyelid closure
during EBC. We will examine how SK2-dependent intrinsic plasticity contributes to response strengthening,
with a focus on possible roles of dendritic calcium spikes in synapse stabilization and clustering, motifs that
have been identified as important cellular mechanisms in hippocampal place field formation. Using genetically
modified mice with blockade of intrinsic plasticity (L7-SK2 knockout), LTP (L7-PP2B) and LTD (CaMKII T305D),
respectively, we will further delineate the specific roles of these plasticity mechanisms in map re-organization
and motor learning. Finally, using double-patch recordings from Purkinje cell dendrites and somata in vitro, we
will e...

## Key facts

- **NIH application ID:** 10311479
- **Project number:** 5R01NS062771-13
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Christian Robert Hansel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $474,472
- **Award type:** 5
- **Project period:** 2008-09-30 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10311479

## Citation

> US National Institutes of Health, RePORTER application 10311479, Intrinsic Plasticity and Information Storage in Cerebellar Purkinje Cells (5R01NS062771-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10311479. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*