Anatomical and neurochemical organization of rat locus coeruleus with respect to galanin and the ascending trigeminal somatosensory pathway
Authors:   , Simpson Kimberly Lynne , Waterhouse Barry D. 
Published: July 2024

Previous electrophysiological and behavioral studies suggest, that one role of the locus coeruleus (LC) - norepinephrine (NE) system is to modulate the signal processing capabilities of sensory neurons during arousal and sustained attention. Since the LC - NE system may regulate signal transmission along sensory pathways via anatomically or neurochemically specific efferent Projections, the focus of the present research was to characterize the spatial distribution and peptide identity of LC perikarya and axons that innervate multiple, functionally-related structures along the rat ascending trigeminal somatosensory pathway. The putative peptide transmitter, galanin (GAL), was selected for analysis, because a large population of noradrenergic neurons in the LC express GAL. In addition, the reported lack of GAL-immunoreactive fibers within many efferent targets of the LC offered a second compelling reason to investigate GAL. Fluorescent retrograde tracers were electrophysiological placed in brainstem, thalamic, and cortical whisker-processing areas in order to identify somatosensory projection neurons within the LC nucleus. These sites included relay nuclei associated with the lemniscal (the principle trigeminal nucleus, the ventrobasal thalamic nucleus (VB), and the barrel field cortex), as well as the para-lemniscal (sub-nucleus interpolaris of the spinal trigeminal nucleus, the rostral sector of the posterior thalamic complex, and secondary somatosensory cortex) sub-divisions of the somatosensory pathway. The results indicated that: (1) the major output from the LC nucleus to the somatosensory system is organized with respect to the crossed trajectory of this modality specific pathway; and (2) there is a propensity for individual LC neurons to send axon collaterals to neuronal ensembles engaged in similar sensory functions. Cytochrome oxidase staining and modified immunohistochemical double labeling approaches were employed to investigate whether LC neurons which co-localize NE and GAL selectively innervate specific levels of the trigeminal neuraxis or certain neuronal populations within cytoarchitectonically specialized sub-regions of the trigeminal complex, VB and somatosensory cortex. The data showed that: (1) similar proportions of galaninergic LC neurons project to lemniscal and paralemniscal components of the ascending trigeminal system; (2) GAL-containing projection neurons do not preferentially target specific levels of the sensory neuraxis; (3) fine-caliber GAL (+) terminals are randomly distributed throughout each trigeminal relay, while large-varicose GAL (+) fibers are only present along the medial border of the reticular thalamic nucleus, the dorsal aspect of the zona incerta, and laminae I/II of the spinal nucleus caudalis; and (4) every GAL immunoreactive fiber, which demonstrates a thin morphological profile, co-stains for the noradrenergic marker enzyme, DBH. Taken together these findings indicate, that the widespread projections of the LC are organized according to the neurochemical identity and anatomical connectivity of LC projection neurons. These organizational features appear to be governed by the functional properties of efferent target sites. As such, differential activation (tonic or phasic) of these patterned outputs could promote selective release of LC transmitter substances within functionally-related neuronal populations. Release of GAL, alone or in combination with NE, along modality specific circuits may significantly modify the processing of sensory information, thereby facilitating and shaping behavioral responses to environmental stimuli.