title: Optogenetic cholinergic modulation of the mouse superior colliculus in vivo.
abstract: The superior colliculus (SC) plays a critical role in orienting movements, in part by integrating modulatory influences on the sensorimotor transformations it performs. Many species exhibit a robust brain stem cholinergic projection to the intermediate and deep layers of the SC arising mainly from the pedunculopontine tegmental nucleus (PPTg), which may serve to modulate SC function. However, the physiological effects of this input have not been examined in vivo, preventing an understanding of its functional role. Given the data from slice experiments, cholinergic input may have a net excitatory effect on the SC. Alternatively, the input could have mixed effects, via activation of inhibitory neurons within or upstream of the SC. Distinguishing between these possibilities requires in vivo experiments in which endogenous cholinergic input is directly manipulated. Here we used anatomical and optogenetic techniques to identify and selectively activate brain stem cholinergic terminals entering the intermediate and deep layers of the awake mouse SC and recorded SC neuronal responses. We first quantified the pattern of the cholinergic input to the mouse SC, finding that it was predominantly localized to the intermediate and deep layers. We then found that optogenetic stimulation of cholinergic terminals in the SC significantly increased the activity of a subpopulation of SC neurons. Interestingly, cholinergic input had a broad range of effects on the magnitude and timing of SC responses, perhaps reflecting both monosynaptic and polysynaptic innervation. These findings begin to elucidate the functional role of this cholinergic projection in modulating the processing underlying sensorimotor transformations in the SC.
authors.affiliation: Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, Colorado; elizabeth.stubblefield@ucdenver.edu.
authors.forename: Elizabeth A
authors.identifier: http://orcid.org/0000-0002-0541-2894
authors.initials: EA
authors.lastname: Stubblefield
authors.affiliation: Department of Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: John A
authors.initials: JA
authors.lastname: Thompson
authors.affiliation: Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, Colorado; Neuroscience Program, University of Colorado School of Medicine, Aurora, Colorado; and.
authors.forename: Gidon
authors.initials: G
authors.lastname: Felsen
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials; D000818:Animals; D005106:Exploratory Behavior / Q000502:physiology; D005453:Fluorescence; D007150:Immunohistochemistry; D008297:Male; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D062308:Optogenetics / Q000295:instrumentation / Q000379:methods*; D009949:Orientation; D010775:Photic Stimulation; D013477:Superior Colliculi / Q000378:metabolism*; D014851:Wakefulness
chemical_list: D000109:Acetylcholine
keywords: brain stem cholinergic system; freely moving animals; in vivo electrophysiology; oculomotor; sensorimotor transformations