RSCHD · Functional dissection of the head-direction circuit in mouse retrosplenial cortex.

Functional dissection of the head-direction circuit in mouse retrosplenial cortex.

The brain's navigational system, which plays a critical role in survival, is highly preserved among mammalian species including rodents and primates. In order to know where we are, we must be able to discern visual and other sensory aspects of the environment, calculate our body position in absolute and relative terms, and retain a memory of where we have been in the past. Although humans and animals are remarkably adept at handling these complex cognitive tasks, many questions remain as to how the brain accomplishes the sophisticated level of multitasking required to maintain and update our navigational awareness. One aspect of the navigation system, the head direction system, allows us to perceive the cardinal direction we are facing in space. This ability is thought to be primarily mediated by so-called head-direction cells, which are preferentially active when we are facing a specific direction. Although head direction cells have been described in the scientific literature for decades, and can be found in multiple brain regions, there are many as-yet unanswered questions as to how the property of direction-selective activity is conferred to these cells, and how the function of head-direction cells in different brain regions differs from each other. The retrosplenial cortex (RSC) is an area of the brain that is highly interconnected with memory-related and sensory-related areas, and contains head-direction cells. Importantly, it is an early target of Alzheimer's disease, and this selective degradation of function may underlie the specific deficits in memory and navigation that is a hallmark of Alzheimer's. However, surprisingly little is known about how the RSC functions in normal brains, and what the unique circuitry of this brain area accomplishes that is critical for memory and perception. The RSC is remarkably amenable to neuroscientific studies using state-of-the-art techniques for understanding brain circuitry. This project aimed to investigate the mechanisms of head-direction tuning in the RSC, and how this feature of the navigational system is built up from inputs from other cells and brain regions. We also aimed to understand the individual features of head direction cells, such as their location in the RSC and their molecular characteristics. As the global population ages, dementia will become a more pressing issue for healthcare systems, societies and families. By applying modern tools to long-standing questions of fundamental brain function, we hope to provide answers that can inform cutting-edge therapeutic avenues for dementia.

Data: CORDIS, © European Union