Functional Investigation of a Brainstem Excitatory Connection Relevant to Sensorimotor Gating

摘要

To focus attention, our brain has to "gate" or block irrelevant sensory information that could lead to brain overload. This is done by way of a neuronal pre-attentive mechanism termed sensorimotor gating (SG). Therefore, deficits in the SG mechanism prevent patients from focusing attention. SG deficits have been observed in patients suffering from various neurological disorders, and it is a hallmark of schizophrenia. Previous work has identified key brain areas, such as the pedunculopontine tegmental nucleus (PPTg), that send inputs to the brainstem to regulate SG. However, there is still a knowledge gap concerning what cell types are involved and what other brain areas could potentially contribute to SG. Our objective in this study is to further identify the cell types located in the PPTg that contribute to SG. The caudal pontine reticular nucleus (PnC) is the brainstem area at the center of the SG circuitry. It has been long known that the PPTg contains cholinergic, glutamatergic and GABAergic neurons and sends direct inputs to the PnC, modulating SG. Recently, the contribution of cholinergic neurons to SG has been shown to be minimal. Therefore, it is not known whether other PPTg neurons project to the PnC and whether they contribute to SG. We Investigated the role of the PPTg glutamatergic inputs onto the PnC in the context of SG, which had not been demonstrated before.;To test our hypothesis, we used neuronal dyes to label cellular pathways, immunohistochemistry to reveal cellular neurochemistry and in vivo optogenetic to functionally study the contribution of the PPTg-PnC glutamatergic connection to SG. Our data show for the first time that there is a direct glutamatergic connection between the PPTg and the PnC, and that it does contribute to SG in vivo.