Flicking the switch: cross-species translation of rapid context-based switching between tasks

Successful interaction with a constantly changing world requires behavioral adaptation. Unraveling the mechanisms underlying flexible control is essential to stimulate advances in the treatments of disorders where deficits in these functions are a core symptom, such as schizophrenia and Parkinson’s disease. For humans, this type of behavior is commonly assessed using the task-switching paradigm, which uses cues to instruct on a trial-by-trial basis which of two tasks to perform. Comparing behavior when the task is repeated to when it is switched allows measuring rapid behavioral adaptations. Existing tests of behavioral flexibility in rodents (e.g. set shifting tests) often assess the ability to learn that a rule changed, yet real-life situations often entail contextual cues explicitly indicating that changes in behavior are required. In addition, current shifting paradigms do not allow assessment of trial-by-trial switching between tasks, as human assays do. An important step in preclinical animal research is to develop tests of behavioral flexibility that directly translate between species.

Previous research I have conducted used a combination of brain imaging, stimulation, and pharmacology to assess the neural basis of adaptive flexible behavior in humans. My work revealed important roles for the striatum, prefrontal cortex, and the neurotransmitter dopamine in task switching. However, these approaches lack the spatial and pharmacological specificity required to answer questions about the causal and specific role of these regions and transmitter systems. Thus, to complement my work with human subjects, I used a novel translational version of a human task-switching paradigm that is suitable for testing in rodents.

In my post-doctoral work, I aim to fully explore the contribution of specific brain circuits to these processes (focusing on the striatum and prefrontal cortex). I will also investigate how the transmission of the neurotransmitters dopamine and gamma-Aminobutyric acid (GABA) mediate successful task-switching. This is important because dysfunction in these transmitter systems underlie numerous psychiatric disorders associated with impairments in these functions, such as schizophrenia and Parkinson’s disease. These studies will be complemented by those using temporally-discrete optogenetic silencing. This will allow the trial-by-trial manipulation of brain circuits and clarify the precise moments when activity in these circuits are necessary for facilitating flexible behavior.