Comprehensive Behavioral Analysis of Opsin 3 (Encephalopsin)-Deficient Mice Identifies Role in Modulation of Acoustic Startle Reflex

Abstract

Opsin-3 (Opn3, encephalopsin) was the first nonvisual opsin gene discovered in mammals. Since then, several Opn3 functions have been described, and in two cases (adipose tissue, smooth muscle) light sensing activity is implicated. In addition to peripheral tissues, Opn3 is robustly expressed within the central nervous system, for which it derives its name. Despite this expression, no studies have investigated developmental or adult CNS consequences of Opn3 loss-of-function. Here, the behavioral consequences of mice deficient in Opn3 were investigated. Opn3-deficient mice perform comparably to wild-type mice in measures of motor coordination, socialization, anxiety-like behavior, and various aspects of learning and memory. However, Opn3-deficient mice have an attenuated acoustic startle reflex (ASR) relative to littermates. This deficit is not because of changes in hearing sensitivity, although Opn3 was shown to be expressed in auditory and vestibular structures, including cochlear outer hair cells. Interestingly, the ASR was not acutely light-dependent and did not vary between daytime and nighttime trials, despite known functions of Opn3 in photoreception and circadian gene amplitude. Together, these results demonstrate the first role of Opn3 on behavior, although the role of this opsin in the CNS remains largely elusive.

Significance Statement

Despite developmental and adult expression of Opsin-3 (Opn3; encephalopsin) in the cerebral cortex, striatum, thalamus, cerebellum, vestibular and auditory structures, and numerous nuclei of the hypothalamus and brainstem among other areas, mice that lack Opn3 have remarkably normal performance in a variety of cognitive, motor, and auditory tests. This study identifies a role for Opn3 in the potentiation of the acoustic startle reflex (ASR) as the first function of Opn3 on behavior. While most behaviors assessed do not vary between Opn3-expressing and Opn3-deficient mice, this study establishes an important baseline into the behavioral physiology of Opn3 and provides the first insights into the functions of Opn3 within the central nervous system.