Acetylcholine dynamics in the retrosplenial cortex during spatial uncertainty

Learning and memory are among the most fundamental cognitive processes, enabling us to use past experiences to solve problems and adapt to an ever-changing world. Acetylcholine (ACh), a key neuromodulator, plays a crucial role in regulating these processes. This project aims to uncover how ACh influences the neural mechanisms underlying learning and memory in the brain's neocortex.

The retrosplenial cortex (RSC) is a critical hub within the brain's learning and memory circuits. It plays an essential role in integrating and distinguishing between aspects of experiences in different locations - termed spatial memories. Notably, the RSC receives dense input from cholinergic (ACh-releasing) synapses, suggesting that ACh is integral to processing spatial memories in this region. While we have strong evidence that ACh can reconfigure neural activity in the RSC, little is known about how and when it modulates spatial memory processing.

Aims of this project are:
1. To uncover the cellular mechanisms by which ACh regulates neuronal communication in the RSC.
2. To investigate how ACh influences the processing of spatial memories in the RSC.
To achieve these aims, we employ a combination of state-of-the-art systems neuroscience techniques, including electrophysiology, pharmacology, imaging of ACh biosensors to examine cellular and synaptic mechanisms (Aim 1), and in vivo brain imaging and behavioural analysis to assess contributions of ACh to memory processing (Aim 2).

By establishing a new foundation for understanding how ACh regulates cognitive processing in cortical circuits, this research will provide critical insights into how disruptions in ACh signalling contribute to learning and memory deficits in neurological conditions such as Alzheimer's disease. Furthermore, it will enhance our understanding of how ACh-boosting drugs, such as donepezil, improve cognitive function.