Ascending noradrenergic excitation from the locus coeruleus to the anterior cingulate cortex

Abstract

Anterior cingulate cortex (ACC) plays important roles in sensory perception including pain and itch. Neurons in the ACC receive various neuromodulatory inputs from subcortical structures, including locus coeruleus noradrenaline (LC-NA) neurons. Few studies have been reported about synaptic and behavioral functions of LC-NA projections to the ACC. Using viral-genetic method (AAV-DIO-eYFP) on DBH-cre mice, we found that LC-NA formed synaptic connections to ACC pyramidal cells but not interneurons. This is further supported by the electron microscopic study showing NAergic fibers contact the presynaptic inputs and post-synaptic areas of the pyramidal cells. NA application produced both pre-and post-synaptic potentiation effects in ACC excitatory transmission in vivo and in vitro. Activation of LC-NA projection to the ACC by optogenetic method produced enhancement of excitatory transmission in vitro and induced scratching and behavioral sensitization for mechanical stimulation. Our results demonstrate that LC-NA projections enhance or facilitate brain responses to pain and itch by potentiating glutamatergic synaptic transmissions in the ACC.

Locus Coeruleus Activation Patterns Differentially Modulate Odor Discrimination Learning and Odor Valence in Rats

“…Other differences in target area receptor-recruitment as a function of activation frequency have also been described. Koga et al. (2020) compared 1 min of 5-Hz or 20-Hz light trains on LC fibers entering anterior cingulate cortex.…”

Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice

“…LC-NAergic neurons also send ascending projections throughout the brain that modulate several key brain functions [ 38 , 40 ]. Recently, it was reported that the activation of LC-NAergic neurons that project to the anterior cingulate cortex induces scratching behaviors [ 41 ]. Thus, it is possible that ascending and descending LC-NAergic neurons play a distinct role in the control of itch behavior.…”

Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation

“…The brain was then removed and dehydrated with 30% sucrose overnight at 4 C. Transverse sections (30 mm) of brain samples containing the ACC and PVN were immunostained with GFP IgG (1:500, ab5450, Abcam) conjugated Alexa 488 conjugated donkey anti-goat IgG (1:1000, ab150133, Abcam). ACC areas were then observed under confocal microscope (Fluoview FV1000, Olympus, Tokyo, Japan) under appropriate filter for Alexa 488 for checking PVN-ACC projecting fiber expression (Chen et al, 2018;Koga et al, 2020).…”