Studies on cognitive behavior in normal and disease model mice using touch screen-based operant conditioning

Abstract

Touch screen test is a recently developed cognition testing tool. Based on operant conditioning, touch screen test enables to test cognition of animals by scoring their cognitive response to visual stimulus presented on LCD monitor. Compared to traditional cognition testing tools, touch screen test has its own advantage in testing cognitions of animals, such as automaticity, the variety of testing cognition types, and translation to human cognition. In spite of these advantages, the real value of touch screen as a cognition testing tool is not fully proven yet. Until a recent date, touch screen has been mostly used to examine the functional roles of a brain region in the specific cognition or to reveal cognitive impairment in transgenic animals, all of which are also possible to investigate by traditional cognition testing tools. In this study, I evaluated the use of touch screen as a tool of testing mices cognition with more detail and multiple purposes. To do this, I first showed that mice can perform delayed match to location based working memory task in touch screen. I also showed that touch screen can not only assess working memory itself, but also measure the reaction time of animals during cognitive decision with high accuracy. I found that slight but very significant different reaction time between when mice made correct and incorrect choice, which may have important implication. I also combined touch screen with optogenetics tool to trigger laser output in automatic and programmed manner. With this automatic optogenetic tool, I tested whether optogenetic activation of dopaminergic neurons can reinforce touching behavior without any natural reward. I first injected adeno-associated virus (AAV) encoding channelrhodopsin 2 (ChR2) into ventral tegmental area (VTA) of tyrosine hydroxylase-cre (TH-cre) mice, to express ChR2 specifically in dopaminergic neurons in VTA. I also designed to trigger optogenetic laser output in contingent with touching visual stimulus. I found that automatic and touch screen mediated optogenetic activation can reinforce touching behavior without any natural reward. Finally, I investigated cognition disability of Parkinson disease (PD) model animal. Conventional cognition testing tools have limitations in testing cognitions of animal models which have motor impairments. By virtue of low motor demand of touch screen test, I could assess cognitive disability of PD model animals in spite of their motor output deficits.