Locus coeruleus modulates locomotor activity via the medial septum and the diagonal band of Broca

Abstract

The locus coeruleus (LC) is positioned in the brainstem and one of the main sources of norepinephrine in the brain. With its projections throughout the whole brain, the LC plays an important role in regulating the general level of arousal and in motivation. The present study aims to identify specific anatomical and functional connectivity patterns between the LC and cell populations in the medial septum diagonal band (MSDB). The direct activation of tyrosine hydroxylase positive neurons in LC has been shown to induce general locomotor arousal and changes in the hippocampal theta activity (Carter et al. 2010). It was shown, that the MSDB is integrated into locomotor activity and controls hippocampal locomotion dependent theta oscillation (Fuhrmann et al. 2015). In this study LC afferent fibers in the MSDB get activated optogenetically in order to investigate if noradrenergic input modulates MSDB activity and alters running behavior. Histology of Th-Cre mice with EYFP Injections in the LC confirms projections to the MSDB area. The results of this study indicate that optogenetic stimulation of noradrenergic locus coeruleus afferents in MSDB leads to increased running behavior in terms of running duration and running initiations but not velocity. Follow-up slice preparations of MSDB placed on a multi electrode array can be used to monitor spontaneous in-vivo like network and single unit activity. 15% of these units increase their firing when noradrenergic afferents are stimulated. Also, 30% of all recorded Units are theta modulated, but no effect on theta modulation could be observed. The two dimensional structure of the MEA allows to further distinguish between dorsal and ventral distributed unit populations within the MSDB. Differences in firing frequency and burst probability along the coronal section of the MSDB indicate a heterogeneous LC input with a majority of noradrenalin sensitive cells in the dorsal MS, rather than the DB.