A flash of light in a rat’s brain can make a brand-new object feel instantly familiar. Researchers have discovered that activating specific memory neurons in the perirhinal cortex tricks the animal into judging any object as “familiar,” even when it has never seen it before. This reveals a fundamental gap in knowledge: we understand how the brain identifies and stores objects, but not how it *uses* those memories to guide decisions—a process often disrupted in dementia. The project will map two separate neural pathways from the perirhinal cortex: one to the frontal cortex for cognitive judgments (familiar versus novel), and another to the visual cortex for perceptual discrimination (same versus different). By using advanced optical techniques in a next-generation animal model with sharp vision and a compact brain, the researcher will activate or silence each pathway during specific tasks to see which one controls which type of decision. This is fundamental science. If successful, it will dissect visual cognitive decision-making into distinct circuits, laying the groundwork for understanding how those circuits break down in dementia and other visual cognition disorders. Such circuit-level knowledge could eventually guide more targeted therapies, but the immediate impact is a paradigm shift in how we study the neural basis of cognition itself.
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Aim The ability to use memory to discriminate objects and react accordingly is fundamental to human behaviour but is often disrupted in clinical conditions like dementia. Upon seeing an object, we perceive its appearance, evaluate its familiarity, and recall its name, functions, and past interaction. With memory, we can discriminate familiar objects better than novel objects. Previous studies elucidated how visual objects are identified, memorised, and recalled. However, how object memory is ‘used’ to influence behaviour remains poorly understood. Uncovering its mechanisms will greatly advance our understanding of visual cognition and its disorders. I aim to determine the neural circuits involved in using object memory. Transformative Objective In perception and memory of visual objects, a brain area called perirhinal cortex plays essential roles. I pioneered an optical approach to cognitive neuroscience, where we used light-gated proteins to control genetically-targeted neurons by light during a cognitive task. I discovered that optically activating object memory neurons in the perirhinal cortex caused the animals to judge any presented object as “familiar” even when novel. This finding of a memory signal within the perirhinal cortex has opened a new possibility for studying neuronal circuits by which object memory is used in visual cognitive decision-making. We can ask: What information does the perirhinal cortex signal to which parts of the brain? Which signal pathway contributes to what aspect of visual cognition? I hypothesise that one pathway to frontal cortex guides cognitive appraisal of an object, while another pathway to visual cortex improves its perceptual discrimination. My objective is therefore to determine if separable projection pathways from the perirhinal cortex impact differentially to cognitive and perceptual judgements about objects. Innovative Approach To study such circuit-specific functions, I have advanced optical techniques and further focused on a novel model species. They can see objects sharply and perform complex cognitive tasks. Their highly evolved but compact brain allows robust viral vector expression and easy access to most cortical areas, making them ideal for the optical approach. Their small body and efficient reproduction enable socially-enriched group housing, use of large numbers required for linking circuit and behaviour, and the creation of genetically-engineered strains and psychiatric and neurodegenerative disease models including dementia. A significant international trend is therefore growing towards this next-generation animal model to study higher cognitive functions and dysfunctions. I will first train these animals in two tasks for cognitive (familiar versus novel) and perceptual (same versus different) discriminations of objects. Next, I will localise memory neurons in the perirhinal cortex by electrical recording, and then map their activity propagation pathways by their optical activation and whole-brain imaging. Then, I will optically activate and inactivate those pathways during the tasks, and distinguish which pathway is critical for cognitive or perceptual discriminations. My institute has the best possible facility and community for this project. Impacts I will develop a cutting-edge paradigm and dissect visual cognitive decision-making into distinct circuits crucial for perceptual and cognitive components, which is unreachable by existing paradigms. My project lays the groundwork to study detailed circuit-processing mechanisms for visual cognition and understand circuit-impairments in visual cognition disorders through applying my paradigm to the disease models as well as investigating homologous circuits in humans. This project will significantly advance cognitive neuroscience and brain health, allowing me to lead the paradigm shift to ‘circuit physiology of cognition’.
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