Sex-specific Adaptations of Visual Cortex Function and Energy Usage During Food Restriction in Mice

Core Concepts

Visual cortical function and energy usage are largely maintained in female mice under food restriction, while they are robustly reduced in males.

Abstract

The study examined how food restriction impacts energy usage and visual coding in the primary visual cortex (V1) of adult male and female mice.
Key findings:

To achieve a similar magnitude (15%) and rate of weight loss, females required a 40% greater restriction of daily food intake compared to males.
Serum leptin levels, which regulate energy-saving changes in the visual cortex, were markedly decreased in food-restricted males but only modestly decreased in females.
Molecular analysis and RNA sequencing revealed that food restriction significantly modulated canonical energy-regulating pathways, including AMPK, mTOR, and PPARα signaling, as well as oxidative phosphorylation, in the visual cortex of males but not females.
Using in vivo ATP and calcium imaging, the study found that food restriction significantly reduced V1 ATP usage and orientation selectivity in males, but not in females.
These findings demonstrate that energy usage and coding precision in the visual cortex are largely maintained in female mice under food restriction, while they are robustly reduced in males.
The neocortex, therefore, contributes to sex-specific, energy-saving adaptations in response to metabolic stress. The study highlights the importance of considering sex differences when studying the impact of dietary manipulations on brain function.

Stats

"To achieve a similar magnitude (15%) and rate of weight loss, females required a 40% greater restriction of daily food intake compared to males."
"Serum leptin levels were markedly decreased (-72%) in food-restricted males, but only modestly decreased (-28%) in females."
"In males, food restriction significantly increased AMPK Thr172 phosphorylation (2.9-fold) and PPARα activity, but only modestly increased these in females (1.4-fold and no significant change, respectively)."
"Food restriction significantly reduced V1 ATP usage (24% decrease) and orientation selectivity (27% decrease) in males, but not in females (12% decrease in ATP usage and 13% decrease in orientation selectivity, both non-significant)."

Quotes

"Collectively, our study demonstrates that in times of food restriction, visual cortical function and energy usage are largely maintained in female mice, while they are reduced in males."
"The neocortex, therefore, contributes to sex-specific, energy-saving adaptations in response to metabolic stress."
"Our research highlights the importance of taking into account sex differences when studying the impact of dietary manipulations on brain function."

Key Insights Distilled From

Sex-specific resilience of neocortex to food restriction

by Padamsey,Z.,... at www.biorxiv.org 10-07-2023

https://www.biorxiv.org/content/10.1101/2023.10.06.561185v2

Deeper Inquiries

How do the sex-specific adaptations of the visual cortex to food restriction change with age?

The sex-specific adaptations of the visual cortex to food restriction can change with age. In older mice, the sex-specific impact of food restriction on cortical function may differ from that observed in young adult mice. For example, in older non-cycling female mice with reduced estrogen levels, the resilience of cortical function found in young cycling adult females may not be as pronounced. Studies have shown that sex differences in the metabolic effects of calorie restriction observed in young adult mice are largely absent in older mice. This suggests that the impact of food restriction on cortical function may vary with age and hormonal status, with older mice potentially showing different responses compared to younger individuals.

What are the potential mechanisms underlying the resilience of cortical function in females compared to males during food restriction?

The resilience of cortical function in females compared to males during food restriction may be attributed to several potential mechanisms:

Leptin Levels: Females tend to resist fat loss during food restriction, leading to minimal reductions in serum leptin levels compared to males. Leptin is a key hormone that regulates energy balance and signaling in the brain. The maintenance of leptin levels in females may contribute to the preservation of cortical function and energy usage during food restriction.

Estrogen Signaling: Estrogen, a sex hormone, plays a role in suppressing food intake and promoting energy expenditure. Estrogen can enhance ATP production, sensitize insulin signaling, and regulate mitochondrial function. The differential regulation of estrogen signaling pathways in males and females during food restriction may influence cortical function and energy usage.

AMPK and mTOR Signaling: Energy-regulating pathways such as AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signaling are known to modulate cellular energy usage. These pathways were significantly modulated by food restriction in males but not in females. The differential activation of these pathways in response to metabolic stress may contribute to the sex-specific adaptations of the visual cortex.

Other Hormonal Factors: Besides leptin and estrogen, other hormonal factors and metabolic pathways may also play a role in mediating the resilience of cortical function in females during food restriction. Sex-specific differences in the regulation of these factors could contribute to the observed differences in cortical function between males and females.

What are the implications of the sex-specific impact of food restriction on visual cortical function for studies of cortical processing and behavior in rodents?

The sex-specific impact of food restriction on visual cortical function has important implications for studies of cortical processing and behavior in rodents:

Experimental Design: Researchers studying cortical function in rodents need to consider the sex-specific responses to dietary manipulations. Understanding how food restriction affects cortical function differently in males and females is crucial for designing experiments that account for these differences.

Interpretation of Results: Findings from studies involving food restriction as a motivational tool or experimental condition should be interpreted in light of the sex-specific adaptations of the visual cortex. Differential responses to food restriction between males and females may influence the outcomes of experiments and the interpretation of results.

Biological Variability: Recognizing the sex-specific impact of food restriction on cortical function highlights the importance of considering biological variability in experimental studies. Researchers should be mindful of potential sex differences in cortical processing and behavior when analyzing data and drawing conclusions.

Clinical Relevance: Understanding how sex-specific factors influence cortical function in response to metabolic challenges can have implications for translational research and clinical studies. Insights gained from rodent studies may inform our understanding of sex-specific responses to dietary interventions in humans and help tailor treatments accordingly.