The Maimon lab aims to understand how brains internally compute and store the value of quantitative variables–like heading angles, spatial distances, time intervals, and event probabilities–and then use these variables to guide behavior. By studying this topic in Drosophila, a classic genetic system, one long-term goal is to better understand how molecules, through their effect on cellular electrophysiology, impact memory and cognition.

Since the 1960’s, it has been widely accepted that explaining animal behavior requires more than defining stimulus-response relationships. Rather, cognitive processes like spatial attention, reward expectation, sensory prediction, and the construction of internal spatial maps, seem to serve a fundamental role in modifying these relationships. Yet, conceptual frameworks for thinking about such internal processes, and our understanding of their neural implementation, remain in their infancy.

Work in the Maimon lab is inspired by the observation that insects, despite having tiny brains, appear capable of performing specific cognitive operations extremely well. For example, desert ants know if they are 30 or 90 m away from the nest and honeybees communicate, with the waggle dance, if a flower patch is 30˚ or 90˚ to the left of the sun. By seeking comprehensive descriptions of how insect brains perform such quantitatively accurate internal calculations, the Maimon lab aims to provide inspiration on how to better understand cognition in larger brains.

The lab studies the genetically tractable fruit fly, Drosophila melanogaster, and has pioneered one of the primary approaches it uses. The technique involves monitoring or perturbing activity in neuronal circuits in flies as they perform flight or walking behaviors, glued to a tiny platform.

A fly performing tethered flight while glued to a custom platform (top), and a membrane voltage trace from a single neuron recorded from the fly brain during this flight bout (below). This neuron in the visual system shows changes in its membrane potential––which are flight-turn-related silencing inputs––whenever the fly performs a rapid turn with her wings.

In recent work, the Maimon lab found that flies are partially blind each time they make a rapid flight turn. This happens because every time a fly turns, the image of the world sweeps over the retina and the fly needs a mechanism to ignore this large self-generated sensory stimulus. The lab has discovered that fly visual neurons receive a quantitatively tailored, internally generated silencing input during turns. When humans make rapid eye movements, our brains face the same problem: We need to ignore the self-generated visual input caused by these movements. The silencing mechanism discovered in flies may illuminate similar processes in our own visual system.

In another line of work, the Maimon lab has described how the fly brain constructs an internal sense of angular orientation. Humans too have a robust sense of orientation, and its importance is made clear when we become disoriented upon exiting a subway station, or in the early stages of Alzheimer’s disease.

A fly glued to a custom platform walks in place, rotating an air-supported ball underneath. The fly’s left and right turns are linked in closed-loop, with minimal latency, to the movements of a vertical blue bar on a panoramic LED display surrounding the fly. The blue bar simulates a fixed landmark located far away from the animal (like the sun or a distant mountain) which indicates the fly’s orientation in the virtual environment. Neural signals recorded in a structure called the protocerebral bridge are shown above the fly. These signals shift left and right along the bridge in lock step with the fly’s clockwise and counterclockwise rotations of its body, serving as an internal, compass-like signal that indicates the fly’s angular orientation in the virtual world. Similar compass-like neural signals are likely used by many insects to guide spatial navigation.

Specifically, the Maimon lab has characterized a neuronal circuit in the Drosophila central complex-a set of structures in the middle of the fly brain-that allows flies to build and update an internal compass-like signal. This circuit operates even in complete darkness, wherein flies must internally integrate how much their legs are turning to update their sense of angular heading. The central features of this biological circuit are analogous to computational models proposed for how rodents build an internal sense of orientation, and may thus inform how any neural system performs mathematical integration.

The lab continues to study how flies calculate quantitatively accurate, spatial and nonspatial variables, and use these to guide behavior. This research program provides a platform for discovering basic mechanisms of how brains integrate, think, and decide.