# Effects of dietary restriction on age-related neurophysiological adaptations: frombehavior to single dopaminergic neurons

> **NIH NIH R01** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2020 · $357,725

## Abstract

Aging is associated with a decrease in movement and cognition, and understanding the neurophysiological
bases of these behavioral deficits will be key to increasing healthspan. Dopamine neurons in the substantia
nigra are key central mediators of voluntary movement and reward-related behavior, and the function of these
neurons is known to decline with age. Unfortunately, little is currently known about how normal aging affects
the specific intrinsic channels and synaptic inputs that are responsible for dopamine neuron excitability and
function. Our lab has developed reliable methodology for making electrophysiological recordings of dopamine
neurons in brain slices from mice of advanced age, thus a comprehensive investigation into the effects of aging
on ion channel physiology in these neurons is now possible. We will combine electrophysiology, behavior,
gene expression analysis, and optogenetics to elucidate the effects of aging on ion channel signaling and
dopamine-mediated behaviors. Furthermore, we will use dietary restriction (an established healthspan-
increasing intervention) to identify the ionic mechanisms that counteract age-related deficits in behavior.
Our central hypothesis is that age-related deficits in movement and reward-related behaviors can be
attributed to specific ion channel conductances in substantia nigra dopamine neurons, and that these deficits
can be attenuated by dietary restriction. Aim 1 is to determine the relationship between age-related deficits in
specific ion channel currents and cell firing. We will also relate (in individual mice) our electrophysiological
findings in single neurons to previously obtained locomotor behavioral data. Aim 2 is to determine the effects of
aging on excitatory inputs from the hypothalamus to dopamine neurons as well as reward-related behavior. For
this aim we will employ optogenetics to study identified glutamate inputs in a brain region-specific manner. Aim
3 is to determine the effects of aging on dopamine autoreceptor-mediated neurotransmission. Aim 4 is to
determine the effects of dietary restriction in aging mice as an intervention that can counteract age-related
decline of ion conductances in dopamine neurons and related behaviors. These studies will provide the first
detailed understanding of the relationship between aging, dopamine neuron activity, and dopamine-mediated
behaviors, and determine the protective effects of dietary restriction on these parameters.

## Key facts

- **NIH application ID:** 9928373
- **Project number:** 5R01AG052606-06
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Michael J Beckstead
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,725
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928373

## Citation

> US National Institutes of Health, RePORTER application 9928373, Effects of dietary restriction on age-related neurophysiological adaptations: frombehavior to single dopaminergic neurons (5R01AG052606-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9928373. Licensed CC0.

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