Novel techniques for the study of drugs and behaviour

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Special Issues are a particular feature of Behavioural Pharmacology: every year since Volume 1 in 1990 has seen the publication of at least one Special Issue. The aim of this Special Issue on ‘Novel Techniques for the Study of Drugs and Behaviour’ was to provide a showcase for recent technical advances in areas such as gene editing, optogenetics, neuroimaging and others that provide novel opportunities for neuroscience. It will not disappoint: all these techniques and more are represented, in three reviews and six empirical papers. Just as happened when genetically modified animals appeared on the scene 25 years ago, these techniques, collectively, are likely to radically change the way in which behavioural pharmacologists work.
The first review paper, by Zelena and colleagues, provides a methodological treatise on optogenetics, a technique in which genes for light-sensitive proteins are introduced into the brain and light signals are used to control the activity of the cells in which the genes are expressed. Optogenetics was awarded the title of ‘Method of the Year’ by Nature Neuroscience in 2010. At that time this was a new technique, with fewer than a hundred publications overall, but it has exploded in popularity and now sees some 5–600 publications a year. The review by Zelena and colleagues summarizes the technical considerations governing the choice of vector (typically an adeno-associated virus) and light-sensitive channel, the pattern, intensity and timing of the stimulation protocol, and, where genetically modified animals are used, the choice of mutant strain. We anticipate that this review will come to be seen as essential reading for anyone using or planning to use optogenetic techniques.
The second review paper, by Maltbie and colleagues, considers the use of functional MRI studies to understand the pharmacology of ketamine, which has long been used as a pharmacological model for schizophrenia, but more recently has emerged as a potential treatment for treatment-resistant depression and suicidal ideation. The review focuses on a systems-level approach showing that ketamine produces robust and consistent effects at the whole-brain level that are conserved across humans and nonhuman primates. The authors argue, based on functional MRI evidence, that the therapeutic potential of ketamine may be derived from a strengthening of executive control circuitry, making it an intriguing candidate for the treatment of drug abuse in addition to its other therapeutic applications.
A third review, by Kangas and Bergman, presents an overview of touchscreen technology in the study of cognition-related behaviour. Touchscreen technology was introduced for human experimentation some 25 years ago and later extended to nonhuman primates and rodents. A recent development, reviewed here, is the availability of flexible experimental designs under the control of the experimenter. The authors provide a primer on the construction of a touch-sensitive experimental chamber, and present data from a proof-of-concept study examining cross-species continuity in performance of a repeated acquisition task across a diverse assortment of animals (rats, marmosets, squirrel monkeys, rhesus macaques). The results illustrate how contemporary touchscreen methodology can be tailored to desired experimental goals and adapted to provide formal similarity in cognitive tasks across species, with high translational potential.
The first two empirical papers present studies using gene-editing techniques. Woloszynowska-Fraser and colleagues used a Cre-recombinase-dependent adeno-associated virus to block neural transmission specifically in parvalbumin-positive GABAergic neurons of the limbic and infralimbic prefrontal circuitry. These cells are critical for the control of network activity, particularly the gamma-frequency oscillations that are prominent during working memory, and are thought to be dysfunctional in schizophrenia. The modified animals presented with increased anxiety and impaired working memory, as well as a lack of behaviourally relevant modulation of gamma oscillations, comparable to endophenotypes of schizophrenia.
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