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Forming Memories, One Neuron at a Time

On Monday, Knowing Neurons highlighted a recent research article that described a new miniature microscope that was small enough to sit on a mouse’s head and light enough to allow it to move freely!  This technology represents a great advancement for the field of neuroscience in general and place cell research, specifically!  For the first time, researchers at Stanford are able to literally watch neurons turn on and off in the hippocampus of a mouse, while it explores an open arena (video), all in real time. This technology adds a new twist on a classic way of studying how the brain maps out the world around us.

In 1971 a research team (O’Keefe and Dostrovsky) at the University College London were recording the electrical activity of neurons in awake rats as they explored an open arena.  As the rat wandered around, O’Keefe noticed that some neurons would only become activated when the rat was in a specific place in the arena.  If the rat meandered away, the neuron would become silent and would stay silent until the rat passed by the same spot again.  Since this neuron was only activated when the rat was at a specific place in the arena, O’Keefe named these neurons place cells.  (You’ll find that scientists generally come up with the most boring names for their discoveries!)

Hippocampus_smallO’Keefe discovered place cells in a region of the brain called the hippocampus.  This brain structure attracted a lot of attention in the late 1950’s when surgeons removed both hippocampi from a man’s brain with the hope of curing his epilepsy.  When the patient awoke from his surgery, the doctors found that his seizures were almost completely gone… but so was his memory!  This patient not only had severe memory loss (retrograde amnesia), but he couldn’t form new memories either (anterograde amnesia)!  Despite this sad outcome, doctors and scientists quickly realized that the hippocampus must be critical for forming and storing memories in the brain.

Neuroscientists have invested a large amount of research into discovering how the hippocampus helps humans and other mammals form and store memories.  Importantly, it seems as if the hippocampus is optimized to store visual or episodic memories, which is why the discovery of place cells in the hippocampus is both exciting and also somewhat expected.  If the brain would like to store episodic memories, it must first form a map of where the individual was in the world when it was learning, and the easiest way to form a map in the brain is to assign a point in space to each neuron.  As an example, the image below shows the path that a mouse took as it wandered around an arena.  If we assume that the mouse was forming a memory in its brain as it explored, then it is very likely that neurons store this information and that they will activate when the mouse re-enters an area that it has already been in.  The cluster of red dots in the lower left of the image shows the region where a single hippocampal place cell activates.

Place Cell Open Field - Cover Photo

Similar place fields can be observed if a mouse or rat walks along a linear track.  After a short amount of time, a small group of neurons begins to show preference for specific parts of the track, until the whole track is evenly represented by the activity of individual neurons!  The gif below demonstrates how these neurons may interact to form simple memories in the hippocampus.

Place Cell Animation

Despite having been studied for nearly 30 years, the biology of place cells is still only partially understood and the hippocampus is still very enigmatic about how it generates, processes and stores memories.  Luckily the research in Dr. Schnitzer’s laboratory has provided a new and powerful approach to studying place cell biology and may play a crucial role in uncovering the mysteries of memories.

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Check back on Friday to learn more about this biotechnology and the company that makes it!

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Written by Ryan Jones.

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References:

O’Keefe J. & Dostrovsky J. (1971). The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat, Brain Research, 34 (1) 171-175. DOI: 10.1016/0006-8993(71)90358-1

O’Keefe J. & Conway D.H. (1978). Hippocampal place units in the freely moving rat: Why they fire where they fire, Experimental Brain Research, 31 (4) DOI: 10.1007/BF00239813

Routtenberg A., O’Keefe J. & Nadel L. (1980). The Hippocampus as a Cognitive Map, The American Journal of Psychology, 93 (1) 177. DOI: 10.2307/1422119

Images adapted from clker and wikimedia commons, made using makeagif.com, and made by Ryan T. Jones.