Cortical circuits underlying flexible learning

Animals survive and compete in their environment by making adaptive memories of the situations they have encountered. Flexible learning then allows to adjust to the great variety of possible environmental changes. This requires comparison of past and present values of rewards and costs associated with behaviour in order to make a decision whether the default course of behaviour needs to be adjusted to the new circumstances. This complex behaviour involves a variety of brain functions, such as detection of the salience of stimuli and its changes, memory of the history of reinforcement, and cognitive control of behaviour. These functions have most consistently been associated with the subdivisions of medium prefrontal cortex and limbic areas of the brain. Within this context, the anterior cingulate cortex (ACC), a prefrontal area, is of special interest due to its specific position within prefrontal and limbic brain systems. ACC has recently been a focus of extensive research in humans, primates and rodents. However, despite a wealth of descriptive data, and numerous theories about the role of ACC in sensory, motor and cognitive processes, it has not yet been possible to combine current views on the function of ACC in cognition into a coherent model.
In my thesis, I explore the role of mouse ACC in flexible learning. I use chemogenetic silencing to locally interfere with the acquisition and consolidation of memory in order to investigate the role of ACC in Pavlovian and non-Pavlovian forms of learning. First, I address the role of ACC in attention set-shifting tasks, which represent a close analogue to the foraging paradigms that have mainly been explored in monkeys. Second, I compare the function of ACC in acquisition and consolidation of single-trial and multi-trial versions of contextual fear conditioning (cFC) learning. By utilising newly available genetic tools, which allow us to selectively silence the group of cells projecting to the area of interest and further manipulate it, I then proceed to a more in-depth study of ACC function within the wider brain network. To this end, I describe in detail the connectivity of ACC with other brain areas, and then address the role of those ACC-based networks in acquisition, consolidation and modification of learning. My results reveal how the function of ACC in supporting flexible learning is embedded dynamically within a specific network of systems, within which specific areas are associated with different forms of subsequent learning. This study provides a comprehensive view of how ACC and the structures monosynaptically connected to it are implicated in the formation of adjustable memories.