Hippocampus-Dependent Goal Localization by Head-Fixed Mice in Virtual Reality

Abstract

The demonstration of the ability of rodents to navigate in virtual reality (VR) has made it an important behavioral paradigm for studying spatially modulated neuronal activity in these animals. However, their behavior in such simulated environments remains poorly understood. Here, we show that encoding and retrieval of goal location memory in mice head-fixed in VR depends on the postsynaptic scaffolding protein Shank2 and the dorsal hippocampus. In our newly developed virtual cued goal location task, a head-fixed mouse moves from one end of a virtual linear track to seek rewards given at a target location along the track. The mouse needs to visually recognize the target location and stay there for a short period of time to receive the reward. Transient pharmacological blockade of fast glutamatergic synaptic transmission in the dorsal hippocampus dramatically and reversibly impaired performance of this task. Encoding and updating of virtual cued goal location memory was impaired in mice deficient in the postsynaptic scaffolding protein Shank2, a mouse model of autism that exhibits impaired spatial learning in a real environment. These results highlight the crucial roles of the dorsal hippocampus and postsynaptic protein complexes in spatial learning and navigation in VR.

Virtual reality method to analyze visual recognition in mice

“…Forth, unlike the OKR, which records a reflex-based response to visual stimulation [ 19 – 21 ], the VR visual tests examine the visual perception of the animal. Finally, this VR behavioral test could be combined with in vivo image recording of CNS neurons in awake animals for correlated study of cellular activity of brain and behavior [ 14 , 29 , 30 ], and therefore, provides a platform to study the cellular mechanisms of visual perception.…”

“…However, Gaffen [ 34 ] raised the possibility that the VR displays could be used by the animals as either a part of the environment or a large object within the actual environment and it may not matter for certain experimental questions. Several more recent studies demonstrated that a complete “immersion” might not be required for mice to identify and approach a visual target in a VR environment [ 5 , 15 , 30 ]. Our results also support the notion that mice can recognize visual cues displayed in partially immersive visual environment and use it for spatial guidance.…”

“…Visual stimulation based VR behavioral tests have been extensively used for memory evaluation [ 10 – 16 , 30 ]. Our results confirmed that the visual memory could last for at least 3 weeks after 3 weeks of training.…”

Context-Invariant Encoding of Reward Location in a Distinct Hippocampal Population

“…This might have reflected reward-predictive cells making a direct contribution to reward anticipation, or they might have received an "efferent copy" of a prediction signal generated elsewhere. It is intriguing that more cells were correlated with behavior during anticipation that required short term memory, which is generally associated with hippocampus-dependent tasks [22,44], and less prevalent when anticipation could have based entirely on immediate cue association, which typically does not rely on the hippocampus [40].…”

Common Defects of Spine Dynamics and Circuit Function in Neurodevelopmental Disorders: A Systematic Review of Findings From in Vivo Optical Imaging of Mouse Models

“…In addition, most experiments discussed here imaged sensory responses under anesthesia. The use of awake head-fixed animals ( Banerjee et al, 2016 ; He et al, 2017 ; Sato et al, 2017a ; Zaremba et al, 2017 ) and miniature head-mounted fluorescence microscopes attached to freely moving animals ( Ghosh et al, 2011 ; Cai et al, 2016 ) will enable imaging of neural circuit activity while mice perform cognitive tasks relevant to the disorder of interest.…”