Technologies
In 1964, the Polish science fiction writer Stanisław Lem published a book he called Summa Technologiae. The title is a reference to Thomas Aquinas’ unfinished synthesis of theological knowledge—Summa Theologiae—written seven centuries earlier. In contrast to Aquinas, Lem attempted in his book not only to summarise the current state of technological knowledge, but also to divine its future. His Summa contains, in addition to several off-the-mark predictions, others that do anticipate present-day technologies. Some are even products or prerequisites of our research.
Lem imagined an approach he called ‘phantomatics’, which resembles modern virtual reality. According to Lem, phantomatics is the generation of ‘realities which for the intelligent life-forms that inhabit them are indistinguishable from normal reality, yet are governed by different laws.’ Virtual reality environments are now a commonplace, and in the laboratory they enable neuroscientists to control the feedback rules by which an animal’s actions change what the animal experiences.
In the reality we normally inhabit we have an expectation of how the exterior world unfolds around us. In virtual reality we can subvert that expectation. For example, we might want to investigate whether a fly has the ability to keep track of its movements by counting the number of steps it has taken, or whether it understands how its position has changed in respect to the environment it inhabits. Placing the fly in a virtual environment allows us to answer such questions decisively.
Lem contrasted his ‘phantomatics’—fooling the brain by providing false information to the senses—with what he termed ‘cerebromatics’: interference with the function of the brain itself. This, too, has become a reality. In our research we commonly take advantage of what are effectively ‘cerebromatic’ methods. We control the activity of specific neurons in the brain—and hence the behaviour of an animal—using techniques such as optogenetics, thermogenetics or chemical genetics.
Electrophysiological and optical techniques are used to examine the structure and function of the nervous system. Individual elements of neural circuits can be labelled and accessed genetically, or by photo-activation or photo-stimulation, and connections can be detected by trans-synaptic complementation or transfer of fluorescent markers. Taking full spatial and temporal control of the incoming wavefront in an optical microscope allows the excitation volume to be shaped for better optical sectioning during imaging and for the tailored activation of light-sensitive molecules. Super-resolution microscopy reveals the arrangements and dynamics of synapses at high resolution.
We observe the output of the brain by tracking and analysing behaviour. The behavioural techniques we use range from those that are basic extensions of the plexiglass arenas first developed in Seymour Benzer’s lab in the late 1960s to bespoke, fully automated, high-tech machines.
The best choice of approach depends on the question being asked of the animal. Some experiments provide a snapshot of a choice, or a statistical picture of the actions taken by a cohort of flies. Others use high-resolution video to provide a detailed live feed of individual behaviour.
Ultimately we aim to observe and control the brain during behaviour. This is hard when an animal is running or flying about. But if the animal can be fixed in space in order to facilitate direct measurement and manipulation of brain activity, ‘phantomatic’ techniques allow us to unfold a virtual reality around the tethered animal.