4. Place Cells in the Hippocampus
Clarke & Taube 2012
Bioradiations
5. Route-Centered Mapping in
the Posterior Parietal Cortex
outbound
L
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goal
start
inbound
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start
goalstart
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35
outbound
R L LR
35
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R L LR
Nitz 2006
6. Behavioral Paradigm • 3 Sprague Dawley Rats
• T-Maze Decision Paradigm
– 28 position blocks
– 5 trials per position
8. Behavioral Results
0
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AL2 DN9 DN10
PercentCorrect
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Sign Test:
-The probability for the rat to
turn correctly is significantly
greater than chance. p=0.004
X2 Results:
-1 and 4 is significantly different
than 2 and 3.
0
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AL2 DN9 DN10
PercentCorrect
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1
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AL2 DN9 DN10
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AL2 DN9 DN10
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9. Rat Correct?
AL2 N
DN9 Y
DN1
0
Y
Rat Correct?
AL2 Y
DN9 Y
DN1
0
Y
Rat Correct?
AL2 Y
DN9 -
DN1
0
-
Rat Correct?
AL2 Y
DN9 Y
DN1
0
Y
10. Implications
• This study affords how the brain achieves high
level cognition
• Application to neurological disorders that
impact higher level cognition
– Fragile X (sensory processing intact)
– Schizophrenia
• In order to study what happens in disorder,
you need to know how it works
– Animal models for neurological disorders
11. Future Directions: Single Unit Recordings
Jeffrey UCL
How does the brain map a fragmented space without a visual boundary?
What happens when the fragment boundary is crossed?
12. Thank You!
Acknowledgements
– Dr. Douglas Nitz
– Laura Shelley
– Desiree Chu
– Shuying Yu
– Stacy Kim
– Scott Ragland
– Jong Park
– Dr. Edmund Chang
• The Rats!
– AL2
– DN9
– DN10
Editor's Notes
Before we get started today, I want you all to rewind through your day and consider how the world is divided around you. Hopefully, you’ve all been outside at some point today… Ok STOP let’s think about that. What divides inside from outside? Maybe walls? The roof? Windows? A door? In this case, there are physical barriers dividing the space.
Here’s another example. As you took your seats in the audience, (Move toward boundary) you all probably didn’t even notice how this room is divided. There is a designated area for the speaker to stand and the audience to sit. While there is no physical boundary separating me from you, somehow the brain has fragmented this room into at least two parts.
Personal space is an abstract social rule in which the boundaries are still not explicitly expressed, but most likely you would not want the creepy guy, sitting behind you, to be breathing on your neck the entire conference.
Slow down and enunciate. Make important points IMPORTANT. Gestures
-Rule Based Fragmentation
Rule-Based Fragmentation: is depend
So let’s take a studio apartment….
On this floor plan there are given dimensions for rooms but there are no walls or doors to divide up the space.
If we place the lines... It is easier to visualize the kitchen CLICK, Living Room CLICK and Bedroom CLICK.
We unconsciously fragment space all the time and we at the Nitz System Neuroscience lab are interested in how the brain navigates through mentally fragmented environments.
In 1948, a cognitive psychologist Edward Tolman coined the term ‘cognitive maps’ that described the ability to commit the mental image of a learned environment to memory. This ‘map’ could then be recalled later to navigate through the environment. Given the apartment example, we want to know how the mental fragments contribute to information encoding process. He theorized that associations made during movement through small bits of an environment could be used to derive an entire map for the environment which, in turn, could be used to navigate to a reward. This spurred interest in how spatial environments were encoded by the brain, leading to the discovery of hippocampal place cells in 1971 by O’Keefe and Dostrovsky.
%The purpose of this research is to determine what is happening at the cell level in the brain as we move through these fragmented spaces.
While organized differently, humans and rats have the same brain regions (hippocampus and posterior parietal cortex) devoted to particular functions of spatial navigation and memory. To investigate what occurs at the cellular level, single unit recording is the method of choice because of its high precision and temporal resolution of brain activity. This technique is mildly invasive and cannot be performed on human subjects.
Place cells refer to cells that are active in particular fields in the environment. Each of these maps shows a top-down view on the environment and the red dots are where the neuron shows firing activity. When the rat moves through this space, the place cell corresponding to this position will fire. On this square environment, the black lines represent the rats movement path and the red dots are the neuronal firing activity, we can see the same trend occurring in the top left of the space. This circular map is similar to a heat map in which the positions with the high activity are shown in red and the low are in blue allowing us to determine the field the neuron is sensitive to. Neurons only fire in relation to a boundaries of the observable environment. So this collection of maps represents a group of place cells that map the whole environment.
Historically, neuroscientists have looked in the hippocampus for spatial navigation but the neuroscientist Mountcastle found neurons in the parietal cortex that map space as well. In 2006, Nitz discovered the parietal cortex is responsible for a relativistic type of mapping which he called ‘route-centric mapping’. He found that as he moved a track around the room, parietal cortex neurons would fire in response to specific inflection points (turns) along the track and the spaces between them, regardless of where the track was in the room. MAIN POINT! The parietal cortex maps the environment differently than the hippocampus.
Complimentary: need to know where you are along a route and also where you are in space
Transition: We want to know how the brain is encoding the space.
We designed a paradigm to test this.
Transition:
This is the T Maze Decision task. Given a specific position in the room, the rat is required to take the left or right path to receive a food reward.
Transition:
The fragmentation rule is depicted here. At position 1 and 2, the rat runs the left route. CLICK. Positions 3 and 4 the rats run the right route. CLICK
Mention the line isn’t actually there.
9 days before introduction of Pos5- 1st trial of each block
The rats were trained on these four positions. The bar charts represents the accuracy of the first trial in each block for 9 days. We used the first trial in the block because it is the only one in the block that the rat must understand where the track is to do the task. On trials 2-5 in a block, it is possible for the rat to repeat his behavior from the previous trial.
We can see that all the rats seem to be performing with high accuracy after training but we used the sign test to statistically verify the rats were performing significantly higher than chance, which ensures they learned the rule.
You can see the performance at Positions 1 and 4 are near perfect, whereas there is greater error at positions 2 and 3 that border the fragments. This makes sense because it is more likely than there would be greater confusion at positions next to fragment boundary.
A Chi Square analysis was run to determine if there was a significant difference between positions away from the boundary versus positions along the boundary line.
Main Point: It’s possible that this paradigm is only testing if the rats are remembering the rule at each position.
In order to rule this out, we tested the rats at new positions in the room that they had not been trained on before. The rule remains the same. Turn right or turn left.
And the rats performed accurately at all new positions.
%Fix the animations.
Transitions: The rats are fragmenting the space. They can perform this high level cognitive task.
Where it happens and by what form it takes.
Next steps: electrophysiological recordings in the hippocampus and parietal ctx to show how the neurons map out rule based fragmentation
----- Meeting Notes (4/13/16 16:31) -----
Fragile X and Schizos have difficulty in higher level cognition.
This fragmentation paradigm is an example of a higher cognitive task.
SUPPLEMENTAL: Walkthrough single unit recording
Be Happy, Be Healthy!
-ChiSquare/day *9/rat probably not significant
-ChiSquare/all days/rat
-if not significant lump rats together
STILL IN ANALYSIS PROGRESS
