Let’s Talk About Neural Time Travel.

Unfortunately Foster has not developed a functional time machine. Instead, he is currently working on elucidating the underlying mechanisms of neural time travel in rats and its role in goal directed navigation. Neural time travel, or chronesthesia, was first proposed by Endel Tulving in the 1980s. It refers to the ability to perceive the difference between perceived, remembered, known, and imagined time. At first glance, this appears to be a thought experiment that will leave you with a headache and not much to show for it but fear not. The basic principle of neural time travel, is the ability to distinguish now from then, whether it is a time in the past or the future. To make a grievous oversimplification, neural time travel is akin to locating memories, thoughts and imaginings in temporal space.

Now, what does this have to do with hippocampal place cells which by definition are interested in physical space?

Pyramidal place cell activity in the hippocampus encodes the spatial relationships between landmarks in the environment. The cells have spatial receptive fields which fire when the animal is in a specific location in the local environment. Each environment is independently represented by place cell activity and the relationship between the spatial fields is unique to each local environment. The firing sequences of the place cells encode the navigation of the animal as it moves through individual receptive fields, in a predictable manner. In addition to place cell activity in navigating animals, these networks of cells additionally exhibit oscillatory activity, hippocampal short wave ripple (SWR)-associated place cell sequences, in sleeping and stationary animals. This feature is the focus of David Foster’s most recent work. The SWR-associated place cell events are also referred to as “replay,” during which time the relative sequence of place cell firing generated by a navigating animal is repeated in a rapid burst.

The hippocampus of rats was implanted with forty tetrodes, to allow monitoring of network activity while the rat navigated through an open field in search of a reward in either a known location or a random location. From this, it was possible to accurately determine the location of the place cell receptive fields making it possible to determine the position and trajectory of the rat from the firing sequence. Foster and colleagues identified many brief increases in population activity in stationary animals. The firing sequence (trajectory event) of many of these events was not random, but encoded a trajectory through two dimensional space that was temporally compressed. Surprisingly, these trajectory events were not simple replay of the animal’s most recent path.

Capture

The end point of these trajectory events was more likely to be the known location of a reward than anywhere else, suggesting that the events are goal directed. Foster also demonstrated that the trajectory represented in these SWR-associated events predicted the actual navigational trajectory of the rat, the prediction was improved if the end point was the location of a known reward, suggesting the events are a reflection of future behavior. By analyzing the trajectory events when the animal was forced to learn a new location for the reward, Foster discovered that initially the trajectory events emphasize novel combinations of start and end points. This is additional evidence that this is not replay of previous firing sequences.

So now you can pretend to understand why the rats are running around in such a seemingly random manner, but how is this neural time travel? The presence of predictive neural firing suggests that the rats are able to utilize episodic memories to facilitate a goal directed future action. Establishing a trajectory from a novel start to a known reward location suggests that the rat is able to extract information from multiple other pathways and string them together in order to get somewhere in the future. There are many implications for how this may allow us to study episodic memory in the future, but I’m pretty sure that the most important finding is that your rats likely know that you were late to feed them yesterday and are probably coming up with a plan to do something about it when you get in to lab tomorrow.

Alex Smirnov is a first year student in the neuroscience graduate program currently rotating with Gentry Patrick. She is a big fan of electrophysiology and unproductive thought experiments.

References

  • Nyberg, L., Kim, A. S. N., Habib, R., Levine, B., & Tulving, E. (2010). Consciousness of subjective time in the brain. Proceedings of the National Academy of Sciences, 107(51), 22356–22359. doi:10.1073/pnas.1016823108
  • Pfeiffer, B. E., & Foster, D. J. (2015). Autoassociative dynamics in the generation of sequences of hippocampal place cells. Science, 349(6244), 180–183. doi:10.1126/science.aaa9633·
  • Pfeiffer, B. E., & Foster, D. J. (2013). Hippocampal place-cell sequences depict future paths to remembered goals. Nature, 497(7447), 74–79. doi:10.1038/nature12112
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