Pharmacological and Physiological Characteristics of Synaptic Transmissions from the Medial Prefrontal Cortex onto Noradrenergic Neurons and Their Presynaptic Neurons in the Mouse Locus Coeruleus

The locus coeruleus (LC) is the primary source of norepinephrine in the brain and is known to modulate brain-wide arousal state. Recent evidence suggests that it also regulates immediate attentional responses by resetting related cortical networks to optimize behavioral outcomes. Cortical regions of high cognitive function, such as the medial prefrontal cortex (mPFC), are theorized to directly influence LC output for the purpose of behavioral regulation. However, the available evidence is insufficient to provide a comprehensive understanding of the underlying mechanisms and properties. To provide further comprehensive data on this issue, we combined ex vivo whole-cell recording with an optogenetic approach to study the synaptic transmission of mPFC inputs to LC neurons, including noradrenergic (NA) neurons and GABAergic neurons presynaptic to them (preLC neurons). Our findings indicate that the mPFC exhibits monosynaptic connections with both NA and GABAergic preLC neurons. These synaptic connections demonstrate cell-type-specific disparities in glutamate release properties. In comparison to those on GABAergic preLC neurons, the mPFC fibers synapsing on LC-NA exhibit a lower release probability (higher paired-pulse ratio) and demonstrate a presynaptic enhancement of glutamate release efficacy during behavior. 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.