# Multiple climbing fiber innervation of Purkinje cells in the adult cerebellum

> **NIH NIH R21** · UNIVERSITY OF CHICAGO · 2021 · $451,000

## Abstract

The architecture of brain circuits plays an essential role in understanding their function. The discovery of
principal concepts in physiology and neurocomputation critically depends on the availability of precise
morphological knowledge. A prominent example supporting this notion is the cerebellum, a brain circuit that is
involved in motor (and non-motor) control and adaptation. At the center of cerebellar circuits are Purkinje cells,
projection neurons that receive thousands of excitatory synapses, which convey sensory information needed
for proper motor control. A hallmark feature of these unique neurons is that they have a massive dendrite that
is innervated, in the adult brain, by one climbing fiber input. The climbing fiber plays a crucial role in theories of
cerebellar supervised learning, and within this conceptual framework provides an instructive signal (here an
error signal) guiding plasticity at parallel fiber synapses. More recent studies have, in addition, pointed out
roles in reward signaling and noted that climbing fiber-evoked complex spikes occur in response to a variety of
sensory stimuli and may also carry motor command signals. These activity-dependent complex spikes are
observed in addition to spontaneous complex spikes that occur at an average frequency of about 1Hz. Thus,
while we do not know what the exact functions of climbing fiber signaling are, it is obvious that this unusual
input provides a core element of cerebellar cortical circuits and to some degree will define its operations. Our
discovery – presented here as pilot data – that a subgroup of the entire adult Purkinje cell population (~15%)
has two climbing fiber inputs instead of just one, that two inputs are almost exclusively observed in Purkinje
cells with two primary dendrites (either separately exiting from the soma, or separating in close proximity to it)
and that within this subgroup 20-25% of Purkinje cells show two climbing fiber inputs, leads to the question
whether there is a functional significance of this double innervation. Is persistent double climbing fiber
innervation of adult Purkinje cells a bug or a feature? In this exploratory study, we plan to examine the
basic phenomenon further and to assess whether two separate climbing fiber inputs may signal independently.
If the answer to our ‘bug or feature’ question is ‘feature’, we will examine consequences for cerebellar function
(e.g. behavioral learning tests) in subsequent studies that we will seek separate funding for. The first aim uses
patch-clamp recordings from mice in combination with confocal microscopy in vitro to test the hypothesis that
the persistence of multiple climbing fibers is not random, but occurs in Purkinje cells with two primary
dendrites. We will also inject tracer dyes into the inferior olive to stain climbing fibers and anatomically confirm
the existence of two climbing fiber inputs. The second aim will add calcium imaging in vitro to examine whether
a double climbing fib...

## Key facts

- **NIH application ID:** 10315621
- **Project number:** 1R21NS124217-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Christian Robert Hansel
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $451,000
- **Award type:** 1
- **Project period:** 2021-06-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315621

## Citation

> US National Institutes of Health, RePORTER application 10315621, Multiple climbing fiber innervation of Purkinje cells in the adult cerebellum (1R21NS124217-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10315621. Licensed CC0.

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