In The Main Olfactory Bulb And Medial Rein In The Nuclear - Nuclear Pathways Between Foot The Function Of The Cholinergic System Research

The main olfactory bulb (MOB) in mammals receives massive centrifugal input from cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, the activity of which is thought to be correlated with animal behaving states such as attention. Cholinergic signals in the bulb facilitate olfactory discrimination and learning, but it has remained controversial how the activity of HDB cholinergic neurons modulates neuronal excitability and olfactory responses in the MOB. We used an optogenetic approach to selectively activate HDB cholinergic neurons and recorded the effect of this activation on the spontaneous firing activity and odor-evoked responses of MOB neurons. Cells were juxtacellularly labeled and their specific types were morphologically determined. We find that light stimulation of HDB cholinergic neurons inhibits the spontaneous firing activity of all major cell types, including mitral/tufted (M/T) cells, periglomerular (PG) cells and GABAergic granule cells. Inhibitions are significantly produced by stimulation at10Hz and further enhanced at higher frequencies. In addition, cholinergic activation sharpens the olfactory tuning curves of a majority of M/T cells but broadly potentiates odor-evoked responses of PG cells and granule cells. These results demonstrate strong effects of the basal forebrain cholinergic system on modulating neuronal excitability in the MOB and support the hypothesis that cholinergic activity increases olfactory discrimination capability. The medial habenula-interpeduncular pathway is a key bridge between limbic forebrain and midbrain monoaminergic centers. Many genes are restrictedly expressed within this pathway and it is also conserved among different species. Previous studies have demonstrated that this axis is related with many behaviors, such as anxiety, pain and stress response, however, the specific behavior function of this axis still remains unclear. Together with optogenetic stimulation, pharmacological methods and in vivo head-fix recording from behaving mice, we found that specific innate aversive stimuli could lead to the activation of cholinergic neurons in the medial habenula (MHB) and the behavioral analysis also suggested that the pathway may relate with anxiety-like behavior. We hypothesized this axis may detect the animal states and mediate innate behaviors to cope with different situations. To testify this, our group is carrying out in vivo recordings through multi-channel electrode to collect more steady signals and qualified cells, what is more, we also care about the synchronization between MHb cholinergic cells, trying to reveal their electrophysiological properties. As for behavioral experiments, we are challenging distinct mouse lines with more high-difficulty paradigms using specific activation and silence methods. Besides, pharmacological interventions are also performed in parallel to confirm and provide more hints for the function analysis. Our preliminary results revealed a possible behavior function of medial habenula-interpeduncular cholinergic pathway, and lay a foundation for the further explorations.