Brain's Cognitive Hub 'Multiplexes' Commands to Arousal Center for Adaptive Behavior

The locus coeruleus (LC) is the primary source of norepinephrine in the brain and is known to modulate brain-wide arousal states. Beyond its role in general alertness, recent evidence suggests the LC also plays a crucial part in immediate attentional responses, essentially 'resetting' cortical networks to optimize behavioral outcomes. High-level cognitive areas, such as the medial prefrontal cortex (mPFC), are theorized to exert direct influence over LC activity to help regulate behavior. However, the available evidence is insufficient to provide a comprehensive understanding of the underlying mechanisms and properties.

To bridge this knowledge gap, scientists employed a sophisticated combination of ex vivo whole-cell recording and optogenetic techniques. This allowed them to meticulously examine the synaptic transmission originating from mPFC inputs onto LC neurons, specifically targeting both noradrenergic (NA) neurons and GABAergic neurons that are presynaptic to them (preLC neurons). Their findings unveiled a direct, monosynaptic connection from the mPFC to both types of LC neurons. Intriguingly, these synaptic connections were not uniform; they demonstrated distinct, cell-type-specific differences in glutamate release properties.

A key discovery was that the mPFC fibers synapsing onto LC-NA neurons exhibited a lower release probability—indicated by a higher paired-pulse ratio—compared to those connecting to GABAergic preLC neurons. Furthermore, the connections to LC-NA neurons showed a presynaptic enhancement of glutamate release efficacy during behavior. As lead author Lai notes in the paper, "The features of simultaneous connections onto LC-NA and GABAergic preLC neurons, which exhibit cell-type-specific differences in plastic function of the transmitter release, enable the mPFC to effectively multiplex information to the LC for the adaptive regulation of behavior."

These findings provide a more comprehensive understanding of the sophisticated neural circuitry underlying cognitive control over fundamental brain states.