Brain Star Award Winner Zaki Ajabi

Dr. Zaki Ajabi, McGill University

Scientific publication

Ajabi, Z., Keinath, A.T., Wei, XX. & Brandon, M.P. Population dynamics of head-direction neurons during drift and reorientation. Nature 615, 892–899 (2023).

A new study reveals how the brain’s internal compass adapts to changing environmental cues to maintain a reliable representation of orientation in space.

The head direction system functions as the brain’s internal compass and underlies a navigator’s sense of direction. In contrast to a magnetic compass, which uses the earth’s magnetic field as a universal reference frame, the brain’s compass relies on local and visual cues to determine orientation in space. In the absence of these cues, significant drift occurs, but the mechanisms underlying this process was little understood. New work by Zaki Ajabi, from McGill University and the Douglas Research Institute, used advanced methods to study activation of head direction neurons to shed light on this important process.

In this study, the researchers recorded the activity of head direction (HD) neurons in a region of the brain called the thalamus, in mice during controlled rotations of a visual landmark. They found that population activity exhibited important variability along two main dimensions. Activity along the first dimension allowed tracking of the animals’ head rotation, whereas activity along the second dimension (referred to as ‘network gain’) emerged under specific circumstances of cue conflict and ambiguity and could predict the HD system’s response to visual cue shifts. Moreover, they showed that, in dark conditions, network gain maintained a ‘memory trace’ of the previously displayed landmark. While the researchers showed that the internal HD representation drifted away from its baseline configuration following visual cue removal (i.e. dark condition), further experiments demonstrated that the HD network could retrieve its original orientation after brief, but not longer, exposures to a rotated cue. This suggests experience-dependent dynamics involving memories of previous associations between HD neurons and cues, in response to visual cue manipulations. Building on these results, they showed that continuous rotation of a visual landmark induced rotation of the HD representation that persisted in darkness, demonstrating experience-dependent recalibration of the HD system. Finally, Zaki Ajabi and colleagues proposed a computational model to explain how the HD network flexibly adapts to changing environmental cues to maintain a reliable representation of HD.

These results challenge previous models of the HD system and provide insights into the interactions between this system and the cues to which it anchors. By recording a very large number of neurons – they increased the number of simultaneously recorded HD neurons by an order of magnitude in comparison with previous attempts – the researchers showed that the internal representation of this network was more complex than tracking an animal’s head orientation only. These findings and methods have the potential to pave the way for a multidimensional appreciation of the complex workings of this fundamental part within the brain’s internal spatial navigation system. Moreover, the computational network model developed based on these may help guide future research in its quest to draw a full picture of the circuitry underlying the generation, maintenance and correction of the HD signal, in changing environments.

These results have clinical relevance given the ubiquity of the HD signal in the mammalian brain and its primordial importance in maintaining a proper representation of space and guiding action during spatial navigation tasks. Interestingly, spatial disorientation is one of the first self-reported symptoms in Alzheimer’s disease. As such, understanding the system responsible for the emergence of directional representation in the brain is crucial to early detection and possible treatment of such cognitive decline.

About Dr. Zaki Ajabi

Zaki Ajabi performed this research as a PhD candidate in the laboratory of Mark Brandon at McGill University. As the first author in this paper, Zaki Ajabi contributed to the experimental design, performed all surgeries, recordings, data analysis and modelling, and also wrote the initial draft and contributed to editing and revising the paper. Zaki is currently working as a postdoctoral research fellow at the Harvard Medical School/Harvard University focusing on the theory of brain navigation.

Sources of funding

This work was supported by funding from the Canadian Institutes of Health Research, the Natural Sciences and Engineering and Research Council of Canada and the Canada Research Chairs Program to Mark P. Brandon.