NeuroNex News

June 2024, Issue #6

From the Lab

Here, we see a virtual environment (top); the first box shows an orange “landmark,” which is missing in the second box. The third box shows the memorized trajectories to that orange landmark, conveying mental travel. Below, we see the sequential activation of neurons in the prefrontal cortex representing the mental path. Image courtesy of Julio Martinez-Trujillo

Researchers Examine How the Brain Memorizes Complex Information The brain can replay short clips of memorized information, such as our trip to an aisle in a grocery store. This ability—referred to as episodic working memory—is crucial to human behavior, deteriorates early in individuals with dementia, and is affected in individuals with schizophrenia. In a recent study, researchers with the NeuroNex project, The Fabric of the Primate Neocortex and the Origin of Mental Representations, showed that holding complex information in working memory happens through the sequential activation of neurons in the brain’s frontal lobe. As part of the research, the team recorded the activity of neurons in the lateral prefrontal cortex of monkeys as they performed a task that involved remembering and navigating to a location in a virtual 3D environment. The subjects saw a visual cue, remembered its location for a few seconds, and then used a joystick to navigate to that spot for a reward. Using a new mathematical technique developed by NeuroNex researchers Lyle Muller and Alexandra Busch, the team analyzed the recordings and found that neurons were activated in specific sequences that represented locations in the virtual environment held in working memory. These sequences were specific to the complex virtual navigation task, while neuronal activity was organized into more fixed persistent firing patterns in a simpler memory task than the virtual 3D environment. Further, blocking NMDA receptors—specific types of receptors in the brain that help neurons communicate with each other—with low doses of ketamine disrupted both these sequences and working memory performance. These findings show a new way, dependent on NMDA receptors, in which the brain encodes visuospatial working memory in complex environments. They also highlight the flexibility of neural codes in supporting working memory in the lateral prefrontal cortex of primates. “The work reveals a long-searched mechanism for episodic working memory in the brain,” says Julio Martinez-Trujillo, NeuroNex project co-PI and author of the recent paper. The NeuroNex team is also focused on better understanding how neurons in the prefrontal cortex that play memory clips deteriorate prematurely in individuals with Alzheimer’s disease.

Trainee Testimonials

Headshot credit: University of Tulsa

Madison Herrboldt is a postdoctoral research associate working on the NeuroNex Project, Odor2Action: Discovering Principles of Olfactory-Guided Natural Behavior. She works in NeuroNex Co-PI, Matt Wachowiak’s lab at the University of Utah, where she studies how different smells are detected and processed in the brain. Specifically, she looks at how inhibitory circuits in the olfactory bulb influence the selectivity of smell or odorant receptors. To study these mechanisms, Herrboldt uses specially modified mice that have tagged odorant receptors, combined with advanced imaging techniques called in vivo two-photon imaging. By comparing data from living organisms (in vivo) and lab experiments (in vitro) with the help of collaborators Hiro Matsunami and Mona Marie at Duke University, the team tests hypotheses on how odorant receptor tuning changes in living systems, the role of inhibition in shifting odorant receptor tuning, and how this inhibition is organized. So far, Herrboldt’s research suggests that odorant receptors are more selective in living organisms than in vitro and that the inhibition process is specific to certain odors and stereotyped across different individuals for at least one type of receptor (Class I). The team plans to extend its research to other types of receptors (Class I and Class II) to understand the general principles of how signals are transformed and how inhibition is organized in the olfactory bulb.

News & Views
Featured Video
Researchers with the NeuroNex Project, Bioluminescence for Optimal Brain Control and Imaging, have developed a video that explains the differences between bioluminescence, fluorescence, and phosphorescence.
Featured Job
The Laboratory of Neural Circuit Modulation in the Departments of Neurology and Neuroscience (Dudok Lab) at Baylor College of Medicine is seeking highly motivated and creative scientists. The applicant will join an NIH-funded lab to engage in basic and translational neuroscience research. The laboratory uses in vivo imaging, electrophysiology and optogenetic approaches to better understand mechanisms that control neural activity dynamics, and to develop strategies to inhibit epilepsy.
Featured Event
The BRAIN Initiative® Conference convenes BRAIN Initiative awardees, staff, and leadership from multiple federal agencies. This open hybrid meeting aims to continue building the BRAIN community, provide a forum for discussing exciting scientific developments and potential new directions, and identify areas for collaboration and research coordination.

What’s NeuroNex?

NeuroNex brings together researchers working across disciplines into a coherent network to develop innovative, accessible, and shared technologies and approaches, as well as theoretical frameworks and computational modeling to advance understanding of brain function across organizational levels and a diversity of species.

NeuroNex News is a quarterly e-newsletter, produced by the NeuroNex Web Team. Contact us at [email protected] with questions, concerns, or submissions.