Kate Falla - The Nuances of Life Encoded: Spatial Context Discrimination (by Danielle Steinbach)

This past Saturday, I was fortunate enough to interview Kate Falla on the NeuroBeacon podcast. Kate is an undergraduate at Columbia who studies spatial context discrimination in mice models with the broader hopes of understanding the mechanism behind spatial memory decline in neurodegenerative diseases like Alzheimer’s. Simply put, spatial context discrimination refers to the ability of people to use their surroundings to differentiate between similar events and objects. 

The idea of context discrimination is one that I briefly mentioned in my previous blog on PTSD because of the way that afflicted patients struggle to distinguish between their traumatic memories and harmless events in their current life. Specifically, I explained that this compromised context discrimination results in patients with PTSD feeling trapped into reliving their most horrifying memories even if theoretically they are now “safe” from whatever trauma they suffered. 

However, before I delve more into the neurological details underlying spatial context discrimination, I’ll start out simple with a background into where this entire field of study in spatial memory began in the 1930s. A century ago – before there was ever fMRI or EEG or two-photon imaging – there was a man, a maze, and a couple of rats. 

Edward Tolman was a researcher fascinated by how reward influences the way we navigate the world around us. Ever reliable as a microcosm of humans, mice were deployed, and with them Edward Tolman plunged into the unknown field of spatial memory. 

The first step Tolman took was allowing the mice to explore all the routes of the maze and discover which paths they could take to most efficiently reach the rewards placed at the ends of different routes. Eventually, the mice learned how to navigate to their expected rewards, the same rush of dopamine guiding them as they bolted in the same directions towards their prize. Then, without warning, Tolman blocked the accustomed paths to the rewards. Believing the promise of reward was required for mice to learn certain routes, Tolman expected the mice to reach the dead ends and remain fixed there, unable to figure out ways to circumvent the dead ends.  

However, the rats exhibited remarkable ingenuity and identified alternate, more circuitous routes to their desired end points in the mazes. The rats’ ability to invent different ways to reach the same destinations in the maze revealed they were not merely memorizing individual routes, but had rather pieced together mental pictures of the entire maze. These experiments were the first to suggest that humans also possess the ability to create what are now known as “mental maps”. 

As modern imaging emerged and researchers accumulated more knowledge about the roles of various regions of the brain, the web of areas involved in spatial context discrimination began to arise. 

Our journey through this interconnected network of brain regions begins with the posterior parietal cortex (PPC), one of the most critical regions for spatial context discrimination. I refer back to one of the critical themes of my blogs, which is that the brain is an interconnected system, rather than a jumble of regions that operate independently. The PPC essentially acts as a communication bridge, intaking real-time sensory information and holding them in short-term working memory, then retrieving memories from long-term storage that share similar features and sensory details. Essentially, the PPC allows us to understand details about our current environment using previous experiences in similar places as a benchmark for comparison. 

To illustrate the importance of the PPC, let’s say that I blindfolded you, led you to a room you’ve never been in, removed the blindfold, and asked you to identify where you were. 

Here is what you see in this room you’ve never visited: small desks arranged in rows facing a whiteboard, stacks of writing and drawing supplies on a table by the door, stacks of papers on a large desk in the corner of the room, and cubbies lining the walls with backpacks stored in them. 

You would immediately be able to tell me that you’re in a classroom, despite the fact that you have never been in that particular classroom. Rather, your PPC relayed all those visual sensory details throughout your cortex and ‘matched them’ with similar memories that have been stored long-term of other classrooms you’ve been in. These memories provided you with enough context to puzzle out your mysterious current situation. 

The PPC thus served a critical evolutionary role of allowing us to make sense of the unknown with all the memories already available to us. Let’s say instead of a comfortable classroom, you found yourself in the middle of a wild terrain or a forest or a cave you needed to navigate as a temporary shelter? The PPC would be all you have to rely on for surviving these scenarios which arose in the everyday lives of our early human ancestors. 

However, the PPC cannot act alone – first, there must be a structure to store those short-term, current sensory details for comparison to long-term memories. This is where the prefrontal cortex (PFC) enters this complex network. A critical region for working memory, the PFC stores salient sensory details in short-term memory so we have sufficient time to process and contextualize the information before us in real-time. However, in addition to simply storing information for us, the PFC also contains neural networks responsible for using and weighing that information so that we can arrive at conclusions about what to do in response to that information. 

The last region I’ll discuss in this overview of the regions involved in spatial memory is the hippocampus. 

Within the hippocampus, researchers have discovered different subregions, including the dentate gyrus, the entorhinal cortex, and the CA1, CA2, and CA3 regions. 

The dentate gyrus famously aids in spatial navigation by encoding the ‘mental map’ that Edward Tolman first observed in mice. With the aid of visual, auditory, tactile, and olfactory details, the dentate gyrus can encode detailed coordinate systems in the brain that allow someone to benchmark their exact location within a broader area. 

Working in concert with the dentate gyrus, the entorhinal cortex allows for the encoding of memories of life experiences, solidifying our contextual understanding of what we see in the present. 

Lastly, that brings us to the CA1, CA2, and CA3 regions of the hippocampus, which intake all the sensory information provided from the dentate gyrus and entorhinal cortex to process distinctions between past and current experiences. In this way, the hippocampus can support a more nuanced view of life and the world around us. 

- Danielle Steinbach

Sources: 

https://achology.com/psychology/exploration-of-the-cognitive-maps-experiment-by-edward-tolman/#:~:text=Edward%20Tolman%20designed%20the%20Cognitive,were%20transformative%20for%20cognitive%20psychology

https://pmc.ncbi.nlm.nih.gov/articles/PMC2823474/#:~:text=4).,discrimination%20than%20during%20intensity%20discrimination

https://www.sciencedirect.com/science/article/pii/S0006899321003097#

https://www.sciencedirect.com/science/article/pii/S0166432817302978#:~:text=In%20addition%20to%20a%20role%20for%20dDG,the%20environment%20such%20as%20shades%20of%20grey

https://pmc.ncbi.nlm.nih.gov/articles/PMC11449717/#sec1

https://www.nature.com/articles/s41467-017-02752-1#:~:text=We%20then%20used%20multivariate%20analyses,details%20that%20support%20vivid%20recollection