Optogenetic and chemogenetic approaches to manipulate attention, impulsivity and behavioural flexibility in rodents

Abstract

Studies manipulating neural activity acutely with optogenetic or chemogenetic intervention in behaving rodents have increased considerably in recent years. More often, these circuit-level neural manipulations are tested within an existing framework of behavioural testing that strives to model complex executive functions or symptomologies relevant to multidimensional psychiatric disorders in humans, such as attentional control deficits, impulsivity or behavioural (in)flexibility. This methods perspective argues in favour of carefully implementing these acute circuit-based approaches to better understand and model cognitive symptomologies or their similar isomorphic animal behaviours, which often arise and persist in overlapping brain circuitries. First, we offer some practical considerations for combining long-term, behavioural paradigms with optogenetic or chemogenetic interventions. Next, we examine how cell-type or projection-specific manipulations to the ascending neuromodulatory systems, local brain region or descending cortical glutamatergic projections influence aspects of cognitive control. For this, we primarily focus on the influence exerted on attentional and motor impulsivity performance in the (3-choice or) 5-choice serial reaction time task, and impulsive, risky or inflexible choice biases during alternative preference, reward discounting or reversal learning tasks.