# Defining the metabolic principles of neuronal network oscillations

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $669,405

## Abstract

PROJECT SUMMARY
Nutrition and fasting have long been known to have major effects on the brain. Previous work linking metabolic energy to
brain function has focused on the neural control of feeding, while key mechanisms by which metabolic states control
cognitive function remain unknown. Here we investigate how different metabolic pathways support the fast spiking of
inhibitory interneurons, which in turn generate gamma oscillations (30-100 Hz) that are linked to cognitive domains such
as memory formation, motor behavior, perception, and consciousness. The subset of fast-spiking inhibitory interneurons
defined by expression of the calcium-binding protein Parvalbumin (PV) are necessary and sufficient to drive gamma
oscillations. These fast-spiking PV interneurons have tremendous energy needs, supported by high metabolism and
mitochondria function. While the extraordinary metabolic activity in PV neurons is well-characterized, the mechanisms
regulating their activity and the consequences of activity regulation on brain oscillations and cognitive function are not
established. We therefore propose to investigate the function of a vertebrate-specific candidate protein (distinctively
expressed in these fast-spiking interneurons) involved in energy generation, and to identify new candidate proteins by a
genetically targeted mitochondrial proteome screen from PV neurons. The main goal of this screen is to identify proteins
that sustain the high energy generation rate as well as proteins that can tune down PV interneuron metabolic activity.
Manipulations of these proteins will then be used to identify the consequences of regulating energy metabolism in PV
interneurons on neuronal network oscillations, with the long-term goal to understand how metabolic homeostasis and
dysregulation in neurons alters brain function in healthy individuals as well as those with brain disorders such as Alzheimer's
disease. Our studies are poised to reveal fundamental insights into the mechanisms that orchestrate energy sources for
network oscillations and that link metabolism to higher order cognitive functions. These insights will form the basis for a
broader understanding of the link between nutrition, brain function and mental health by determining the consequences of
dysfunction of the molecular machinery for energy production in interneurons on brain oscillations that are critical for
cognitive function.

## Key facts

- **NIH application ID:** 10838044
- **Project number:** 1R01NS136048-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Gulcin Pekkurnaz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $669,405
- **Award type:** 1
- **Project period:** 2024-05-15 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10838044

## Citation

> US National Institutes of Health, RePORTER application 10838044, Defining the metabolic principles of neuronal network oscillations (1R01NS136048-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10838044. Licensed CC0.

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