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The Role of Direction-Selective Signaling in Predation

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This Research Insight covers a recent publication from the Kerschensteiner Lab. Here, we highlight how Jenna Krizan, PhD and colleagues added clarity to an ongoing debate about the origin of direction-selective signaling in the brain and explored its role in the predatory behaviors of the mouse.

In their recent paper published in PNAS, scientists in the lab of Daniel Kerschensteiner, MD, professor of ophthalmology at WashU, demonstrate that a subpopulation of neurons in the superior colliculus (SC) of the mouse integrate visual information to guide the predatory behaviors of mice. Here, Jenna Krizan, PhD, a former graduate student in the Kerschensteiner Lab, and colleagues identify a population of retinal ganglion cells that innervate and tune the responses of these SC neurons and further disentangle how the visual information they convey contributes to efficient predation.

Vision for predation

Mice, like many other species, rely on vision to hunt. Previous studies have linked this behavior to populations of neurons in the SC, which help detect motion and trigger appropriate behaviors. This study expanded on previous work to understand the types of visual information that are used to guide hunting.

Jenna Krizan, PhD

To do so, Krizan and colleagues manipulated a population of narrow-field (NF) cells in the SC, which are known for their direction selectivity – responding strongly to motion in one direction and weakly in the opposite – using a combination of viral and genetic strategies in the brain and retina. By manipulating both the flow of information and its tuning properties between the retina, brain, and behavior, the authors were able to determine the origin of direction-selective responses in the SC and the role of this feature tuning in predation.

Direction selectivity in the retina and SC

Visual processing starts in the retina before any light signals are sent to the brain. Photoreceptors sense light and bipolar cells relay this information to the retinal ganglion output cells of the retina. This pathway is refined by modulatory amacrine cells that interact precisely with bipolar cells and retinal ganglion cells, resulting in retinal outputs that encode specific information about the visual scene.

Direction selectivity is first computed in the retina. This feature first arises in direction-selective ganglion cells (DSGCs) due to motion-driven, asymmetric inhibition from starburst amacrine cells (SACs). DSGCs send information about motion direction to visual centers in the brain, which likewise exhibit direction-selective signals.

The origin of direction selectivity in SC

A DSGC (red) in the mouse retina that was confirmed to send visual information directly to NF cells in SC. The DSGC is surrounded by SACs (green) that tune the information transmitted by DSGCs, resulting in direction-selective signaling.

The SC receives direct input from the retina; however, the retinal ganglion cells that innervate NF cells and the origin of their characteristic direction-selectivity were elusive. Here, Krizan and colleagues performed retrograde tracing experiments to identify cell types that innervate the NF cells. They confirmed by electrophysiological recordings, morphology, and immunostaining that DSGCs project directly to the NF cells in SC.

SACs (green) are typically abundant in the mouse retina (control). Using a genetic strategy, the authors successfully deleted nearly all of these cells from the retina, rendering the information transmitted from the retina to brain non-direction-selective.

Given the direct input of DSGCs to NF cells, the authors hypothesized that the canonical direction selectivity of the NF cells might originate in the retina, rather than being computed de novo in the SC. To test this, Krizan and colleagues rendered the output signals of DSGCs non-direction-selective by selectively removing the modulatory SACs from the retina, which tune DSGCs. The authors therefore preserved the strength, but not tuning, of the retinal ganglion cell input to SC. When the authors performed extracellular electrophysiological recordings of the NF cells in SC of mice that lacked direction tuning in the retina, they observed a reduction in their direction-selective responses of the NF cells, indicating that they inherit their tuning properties from the retina.

The role of direction selectivity in predation

A key element of predation is the predator’s ability to respond dynamically and flexibly to the escape attempts of prey, which require the detection of changing motion trajectories. Given the rapid changes in motion direction, the authors interrogated the role of the direction-selective circuitry in the retina and brain in predation.

The authors used a viral and genetic strategy to selectively remove the direction-selective NF cells from the SC. Consistent with previous reports, these cells were crucial to hunting, as the mice lacking NF cells exhibited deficits linked to the detection, pursuit, and capture of their prey.

The authors then decided to probe whether the directional information, specifically, that is encoded by the NF cells is used in the computations leading to predatory behaviors. Krizan and colleagues removed SACs from the retina to render the downstream circuitry in the retina and brain non-direction-selective and then tested the predatory abilities of mice. Regardless of when the circuitry was rendered non-direction-selective – either before or to coincide with behavioral testing – the abilities of the mouse to detect, pursue, and capture its prey were unchanged.

These results suggest that mice do not rely on changes in motion direction to adjust their hunting strategy to respond effectively to changes in their prey’s trajectories. Instead, cells in the SC – including the NF cells – that have been implicated in hunting behaviors must integrate diverse types of information to preserve their ability to generate reliable behaviors. 

Three different mice hunt insect prey. The control mice (left)- which have no visual deficit—and mice in which SACs were deleted from the retina (middle) efficiently hunt prey. In comparison, mice in which NF cells were deleted from SC (right) are considerably worse hunters, as they struggle to detect, pursue, and capture their prey.
About WashU Medicine

WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,900 faculty. Its National Institutes of Health (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 56% in the last seven years. Together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,900 faculty physicians practicing at 130 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.