Our brain provides us with a sense of where we are in space. The importance of this sense is clear when we become spatially disoriented, like when one is confused about one?s orientation after exiting a subway station. Central to the understanding of how brains give rise to spatial cognition has been the discovery of place cells in the 1970?s (i.e., neurons that are active when animals are in one specific location in space), head-direction cells in the 1980?s (i.e., neurons that are active when animals face one specific compass direction), and grid cells in the early 2000?s (i.e., neurons that are active when animals are in a grid of locations in space). A remarkable feature of these cells is that their patterns of firing persist even when animals navigate in complete darkness, wherein the animals must use an internal assessment of their own movements to update their sense of position or orientation. A fundamental next step in our understanding of spatial cognition would be to describe the circuit-level interactions that give rise to such physiological activity patterns and to understand how such cells ultimately influence navigational behavior. Our recent work has uncovered the first neural circuit to explain how heading-related cells update their activity levels when animals turn in the dark. This biological circuit in Drosophila is a realization of a circuit proposed to exist in the mammalian brain twenty years ago, based on computational modeling, but never proven to exist in any animal. Here we focus on three related questions that aim to provide a deeper understanding of how brains construct navigational signals and how these signals guide behavior.
Our first aim i s to identify a circuit path by which sensory information arrives to the central brain to update the head-direction or heading system when an animal turns in the dark.
Our second aim i s to determine the role of heading signals in guiding navigational behavior by perturbing the activity of heading-related cells in animals performing a heading task.
Our third aim i s to characterize new cell classes and circuitry to ultimately inform how brains might solve two-dimensional navigation tasks. The overarching goal of this work is to provide a detailed, circuit-level understanding of how brains compute spatial navigation- related variables. Such discoveries will inform our thinking on how our brains allow us to perform day-to-day navigation tasks, like driving home from work or finding our car in a parking lot, and how to approach psychiatric and neurological conditions in which these abilities are impaired, such as Alzheimer?s disease.

Public Health Relevance

Several dementias, including Alzheimer?s disease, include deteriorations in our ability to understand and remember where we are in space. A richer cellular and circuit-level understanding of how spatial navigation is achieved may inform novel therapeutic strategies for targeting these conditions, reducing the heavy burden they place on individuals and society.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS104934-04
Application #
10075327
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
David, Karen Kate
Project Start
2018-01-01
Project End
2022-12-31
Budget Start
2021-01-01
Budget End
2021-12-31
Support Year
4
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Internal Medicine/Medicine
Type
Graduate Schools
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Green, Jonathan; Maimon, Gaby (2018) Building a heading signal from anatomically defined neuron types in the Drosophila central complex. Curr Opin Neurobiol 52:156-164