# The Nature and Function of Genomic Imprinting in Monoaminergic Neurons

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $724,108

## Abstract

Mental illnesses are complex, affected by stressors and metabolic factors and involve changes to multiple
behavioral components and decision-making processes. Thousands of genetic variants with small effects are
typically involved. Thus, we lack a coherent genetic, cellular and evolutionary model for understanding and
modifying important behavioral components affecting decision-making, activity and stress. If such a
fundamental model of control could be uncovered for conserved, naturalistic behavior, our capabilities
for understanding and therapeutically modifying behavioral disorders would be improved. Foraging has
been studied for decades to uncover the basic principles and mechanisms of decision-making. Studies
typically use simplified binary choice tests. However, we recently published a naturalistic foraging assay and
unsupervised machine-learning methods to study complex, naturalistic decision patterns in mice. We
discovered that foraging is composed of reproducible, genetically controlled behavioral sequences that we call
“modules”. Using these methods, we investigated roles for maternally and paternally imprinted genes in
controlling naturalistic decision patterns in males and females. Canonical imprinting involves complete
silencing of one parent’s allele; however, we previously described genes with “noncanonical imprinting effects”
that involve parental allele expression biases at the tissue level. We now have evidence that noncanonical
imprinting effects at the tissue level involve allele silencing in subpopulations of cells. Moreover, we uncovered
important roles for noncanonical imprinting effects in controlling naturalistic foraging and risk-reward-effort
decision patterns. Currently, we do not fully understand the behavioral roles for different noncanonical
imprinted genes. MEGs (maternally expressed genes) and PEGs (paternally expressed genes) are postulated
to have opposing functional roles, suggesting an enticing genetic and evolutionary model of mammalian
decision control. Imprinting effects in different cell populations could regulate the form, expression, timing
and/or sequential order of different behavioral components of foraging. Therefore, our proposed study tests
the hypothesis that noncanonical MEGs and PEGs have opposing effects on discrete behavioral
components of naturalistic foraging and their cell-type specific imprinting effects reveal cell
populations controlling discrete behaviors. In Aim 1, we will determine how MEGs and PEGs co-expressed
with Th (tyrosine hydroxylase) and Ddc (dopa decarboxylase) in monoaminergic brain cells affect naturalistic
decisions. In Aim 2, we will define functional links between discrete cell populations with imprinting effects for
particular genes and discrete behavioral components of naturalistic foraging and decision patterns. Our
proposed study is significant because it will help define an important genetic, cellular and evolutionary model of
behavioral and decision control. Our l...

## Key facts

- **NIH application ID:** 10491164
- **Project number:** 5R01MH109577-07
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Christopher Gregg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $724,108
- **Award type:** 5
- **Project period:** 2016-03-04 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491164

## Citation

> US National Institutes of Health, RePORTER application 10491164, The Nature and Function of Genomic Imprinting in Monoaminergic Neurons (5R01MH109577-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10491164. Licensed CC0.

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