# Neocortex saves energy by reducing coding precision during food scarcity

## TL;DR

The brain saves energy during food scarcity by reducing the precision of visual information processing, which can be reversed with a hormone called leptin.

## Contribution

The study reveals a novel energy-saving mechanism in the neocortex during food scarcity involving AMPAR conductance and leptin regulation.

## Key findings

- Food restriction reduces AMPA receptor conductance, saving 29% of synaptic ATP use.
- Leptin supplementation restores visual coding precision impaired by food scarcity.
- Reduced coding precision leads to broader orientation tuning and impaired visual discrimination.

## Abstract

Information processing is energetically expensive. In the mammalian brain, it is unclear how information coding and energy use are regulated during food scarcity. Using whole-cell recordings and two-photon imaging in layer 2/3 mouse visual cortex, we found that food restriction reduced AMPA receptor conductance, reducing synaptic ATP use by 29%. Neuronal excitability was nonetheless preserved by a compensatory increase in input resistance and a depolarized resting potential. Consequently, neurons spiked at similar rates as controls but spent less ATP on underlying excitatory currents. This energy-saving strategy had a cost because it amplified the variability of visually-evoked subthreshold responses, leading to a 32% broadening of orientation tuning and impaired fine visual discrimination. This reduction in coding precision was associated with reduced levels of the fat mass-regulated hormone leptin and was restored by exogenous leptin supplementation. Our findings reveal that metabolic state dynamically regulates the energy spent on coding precision in neocortex.

•Food restriction results in ATP savings via reduced AMPAR currents in visual cortex•Concurrent increases in input resistance and resting potential preserve spike rate•These changes amplify response variability, leading to broader orientation tuning•Supplementation with the adipocyte-hormone leptin restores visual coding precision

Food restriction results in ATP savings via reduced AMPAR currents in visual cortex

Concurrent increases in input resistance and resting potential preserve spike rate

These changes amplify response variability, leading to broader orientation tuning

Supplementation with the adipocyte-hormone leptin restores visual coding precision

How does the metabolically expensive mammalian brain adapt to food scarcity? Padamsey et al. show that under food restriction, mouse visual cortical neurons save ATP by decreasing excitatory currents. Compensatory mechanisms preserve spike rate but decrease coding precision of visual information. Supplementation with the fat mass-regulated hormone leptin restores coding precision.