# Physiological Function of Persistent Inward Currents in Motor Neurons

> **NIH NIH R21** · UNIVERSITY OF ARIZONA · 2023 · $408,384

## Abstract

ABSTRACT
 Motor neurons receive synaptic inputs from many other neurons and convert these inputs into
frequency-coded messages that are relayed to muscle fibers to cause contraction. It is often assumed that
motor neurons generate spikes at rates in proportion to the excitatory synaptic input received. It is now
recognized, however, that motor neurons have active processes, such as persistent inward currents (PICs),
that may markedly alter the relationship between synaptic input and firing rate output. PICs represent a
neuromodulator-mediated intrinsic source of membrane depolarization that can even lead to self-sustained
firing of motor neurons, i.e., prolonged spiking in the absence of synaptic input. Several ideas have been
forwarded as to the functional significance of PICs, both in terms of the control of normal motor function and as
an impaired process contributing to various neurological disorders. Indeed, some investigators have
suggested that PICs provide the primary source of depolarizing current to motor neurons during all forms of
activity, whereas others speculate that PICs are only active during periods of high stress and arousal. Yet the
extent to which PICs contribute to natural motor neuron activity is not known. Therefore, the goal of this
project is to directly ascertain the role that PICs play during voluntary muscle contraction using an animal
model wherein the ion channels (L-type calcium), thought to be primary mediators of motor neuron PICs, are
selectively disabled (Aim 1) or enabled (Aim 2). We will do this by recording motor unit activity in plantar flexor
muscles of rats voluntarily exerting target isometric forces in the presence and absence of intrathecally injected
nimodipine, an L-type Ca+2 channel blocker (Aim 1), and serotonin, a known promotor of PICs (Aim 2).
Changes in motor unit firing rate (and recruitment) recorded under drug conditions will be compared to the
same units recorded prior to drug delivery while the animal holds the same force. These comparisons will
provide direct knowledge of the role PICs play in shaping natural motor unit activity – a topic of debate since
the discovery of PICs in the late 1970s. Furthermore, this study will add to our understanding of PIC
dysfunction, implicated in neurological disorders such as spasticity and amyotrophic lateral sclerosis.

## Key facts

- **NIH application ID:** 10663030
- **Project number:** 1R21NS130098-01A1
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** ANDREW J FUGLEVAND
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $408,384
- **Award type:** 1
- **Project period:** 2023-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10663030

## Citation

> US National Institutes of Health, RePORTER application 10663030, Physiological Function of Persistent Inward Currents in Motor Neurons (1R21NS130098-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10663030. Licensed CC0.

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