Working memory in health and disease

Sometimes we only need to remember something for a very short time, like briefly memorising a phone number to dial the correct one. This may sound like a simple task, but such behaviour is detrimentally affected across many neuropsychiatric disorders.
Such symptoms are highly disruptive in daily lives of neuropsychiatric patients, but are very difficult to treat because we do not understand much about the underlying brain mechanisms and how they can fail under certain conditions.
This type of memory in action is known as working memory, to remember relevant information while in an activity. Optimal execution of working memory relies on the correct activity of neuronal circuits in the brain, much akin to electronic circuits.
Neuronal circuits are comprised of many types of brain cells, with the key players being the excitatory pyramidal neurons and inhibitory GABAergic neurons, acting in balance. We do not yet understand how exactly these different types of neurons interact for formation, maintenance and recall of working memory. Additionally, we know that neuronal circuits are also under the influence of chemicals known as neurotransmitters, one of them being serotonin (5HT). 5HT signalling system has been a main target for many neuropsychiatric treatment interventions, but its specific role in the working memory-related neuronal circuit is unclear.
To address this, we will study neuronal circuit activity underlying working memory in the mouse brain, which serves as a prominent model of the human brain and has been shown to display working memory like that of humans. Using the mouse model, we can study brain circuits in ways that are not possible in humans.
We will use cutting-edge new tools and approaches using light to monitor and control neuronal activity while mice perform a behavioural task that requires working memory. Specifically, we will simultaneously monitor the activity of both excitatory and inhibitory neurons during task execution to uncover the relevant neuronal circuit mechanisms.
Next, we will use pharmacological chemicals to modulate the 5HT signalling system to monitor how 5HT regulates these neuronal circuits. We will then use light to specifically and reversibly manipulate the activity of specific types of GABAergic neurons to further delineate their precise critical role in working memory circuits, as dysfunction of the GABAergic system has been implicated in many neuropsychiatric disorders with working memory deficits.