How does the metabolically-expensive mammalian brain adapt to food scarcity?
Information processing is energetically expensive. In the mammalian brain, it is unclear how information coding and energy usage are regulated during food scarcity. I addressed this in the visual cortex of awake mice using whole-cell recordings and two-photon imaging to monitor layer 2/3 neuronal activity and ATP usage. I found that food restriction reduced synaptic ATP usage by 29% through a decrease in AMPA receptor conductance. Neuronal excitability was nonetheless preserved by a compensatory increase in input resistance and a depolarized resting membrane potential. Consequently, neurons spiked at similar rates as controls, but spent less ATP on underlying excitatory currents. This energy-saving strategy had a cost since it amplified the variability of visually-evoked subthreshold responses, leading to a 32% broadening in 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. These findings reveal novel mechanisms that dynamically regulate energy usage and coding precision in neocortex.
Fate and freedom in the developing mammalian brain
While the diversity of neurons in the adult mammalian brain is staggering, these cells emerge from a seemingly limited set of progenitors during development. This begs the question of how complexity emerges from a finite number of elements during dynamic biological processes. Here, I will discuss recent work from my laboratory addressing relationships between genetic diversity and connectivity in single-cell types, and how progenitor diversity may constrain adult brain cellular states during normal and abnormal brain development.