Vorhees and Williams 2014 Flashcards

1
Q

What is navigation and what is it required for?

A

Ability to learn to find a way through an environment without getting lost.
Required for foraging for food/water, finding mates, avoid predators. All essential for survival.

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2
Q

What is an allocentric navigation?
What is a distal cue?

A

Spatial navigation; Ability to navigate using distal cues
Distal cues are landmarks located at a distance and provides place info in relation to other landmarks.

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3
Q

What is an egocentric navigation?

A

Ability to navigate using proximal cuues including internal cues, optokinetic flow, and signposts (=/= landmarks)

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4
Q

What is egocentric further divided into and what are those?

A

1) Route based (striatum)
Relies on internal cues and signposts, to employ a set of rules to navigate (eg. left, right, left turn at each signpost)
Can become habits and thereby implicit memory

2) Path integration
Ability to move to location and back to homebase in a more direct path (vector addition) -> ability to track start location based on self-motion info
EC or HPC lesion doesnt affect this but their activity is recruited.
Moreso temporal lobe

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5
Q

What are the brain regions involved in spatial navigation? (2 most basic, more in the neocortex)
What are the cells involved within each region?

A

1) HPC
- Place cells in CA1/3 subfields that respond to different locations in an environment to form a neural map -> remap when in a new environment

2) EC
- medial EC (layer 2) has place cells connecting with HPC place cells
- grid cells that form tiling patterns with fields larger than place fields
- dorsal has smaller, ventral has larger fields in EC
- head direction cells for orienting direction of movement to distal cues (also found in pre and para subiculum)
- border cells have fields reacting to boundaries of an environment

3) PFC, RSC, ACC, parietal cortex

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6
Q

Difference between semantic and episodic memory and brain networks associated with it?

A

Semantic = facts and locations (extension of allocentric)
Episodic = sequence of events (so egocentric)
Memory storage and retrieval requires neocortex, PFC, RSC,ACC, parietal cortex

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7
Q

Brain regions involved in nonspatial navigation?

A

Overlaps with allocentric system, such as head direction cells in EC, RSC, pre and para subiculum

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8
Q

What is the one principle in spatial nav assessment?
What about nonspatial and how can it be achieved?

A

Must minimize proximal and enrich distal cues
Opposite for nonspatial nav, using darkness for example

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9
Q

Why is MWM appropriate for spatial nav?

A

Minimizes proximal cues by featureless pool

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10
Q

What is the RAM? Describe the sequence of training and testing?
What are its variants? What are some disadvantages?

A

Appetitively motivated task by restricting food
2 versions: working memory and working/reference memory

Working memory version:
First pretrain by placing food throughout maze to encourage exploration. Then test by placing animal in center and placing rewards at end of each arm.
Each re-entry into previously visited arm = mistake in working memory
Working/ref memory version:
Have some arms have rewards and some arms no rewards during training stages. In testing, re-entry to reward arm tests working memory, entry into no reward arm tests reference memory.

Disadvantages
- can solve without spatial navigation (chaining,ie circling in sequence)
- can close off arms after exiting an arm to prevent immediate chaining
- require to balance hunger between animals by achieving 80% body weight
- Has olfactory and proximal cues within maze

Can use radial arm water maze -> Mice tested to avoid an arm by nonmatch to sample task

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11
Q

What is a t-maze and what does it test?
What are the variations?

A

Tests spatial working memory
Spontaneous or reward-based
Reward-based: Place rewards in both arms and close off one arm. Allow mouse to enter and consume reward. Restart but with both arms open. If mouse chooses new arm, it can consume the reward -> Rewarded alternation
Spontaneous: Allow to choose an arm and confine in it for 30sec. Restart and let it choose between the arms -> tendency to explore novel arm by using working memory and distal cues.

Rotate the maze to make sure mice using distal cues and not habit

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12
Q

What is a hole board maze?

A

Tests similar to RAM
Many holes in a board with only a few of them having food reward
If re-enter a food hole -> test working memory
If enter no food hole -> test reference memory

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13
Q

What is a star maze?

A

Swimming maze
Pentagonal maze with proximal cues in the inner walls and distal cues outside
Trained to start at a specific location and specific goal
During test, switch the start location to determine whether egocentric or allocentric navigation used
Mice generally use both equally and we can quantify the proportion of the methods (ie. hippocampal deficit -> more shift towards egocentric)

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14
Q

How do you test for nonspatial navigation?

A

Use a labyrinth maze such as cincinnatti water maze
Or use MWM in darkness (can use the walls as proximal cues)

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15
Q

What are 4 features of MWM?

A

1) Rodents prefer dry land so is a motivation to escape and complete task
2) Featureless inside but rich in distal cues
3) Can assess proximal cue navigation by making visible platform
4) Swim speed can tell differences in motivation and capabilities

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16
Q

What are the 6 advantages of MWM?

A

1) Water-based
Equal opportunity across different weights
2) Task completion
Has near 100% completion rate -> reduced selection bias
3) Task mastery
Has near 100% master rate -> deep learning curve gives sensitivity
4) Minimal training
Very quick learning
Can also use cued version to speed up learning to escape
5) Efficiency
Less off-task behaviors like sniffing and grooming
6) Water motivation is consistent throughout
Motivation doesn’t change (as long as they learn to escape at the begininning) unlike appetitive behavior which can be affected by satiety

17
Q

Are MWM variability in performance attributed to spatial learning?

A

No, mostly attributed to thigmotaxis and floating, which are non spatial learning -> Have to measure search strategy and control for (ie. are they actually using spatial cues)

18
Q

What are possible measures for MWM?

A

Latency, Platform crossover, Time in target, path length, cumulative distance to platform (total distance from each xy position taken corrected by time), corrected integrated path length (deviation from direct path to platform)
CDTP can dissociate certain nonspatial strategies from spatial strategies better and is more sensitive

19
Q

What are the disadvantages of MWM?

A

1) Floating and thigmotaxis -> Use cued navigation before acquisition trials to learn to escape more easily
2) Stress
- Stress promotes motivation if given right amount
- Corticosterone is increased in mice undergoing test
- But mice learn the task well anyway and does not take away from the validity of test for spatial memory

20
Q

In what way is MWM flexible?

A

Can adapt for working memory version (delayed matching to sample)
Can adapt to distinguish HPC vs striatal deficits
- Use patterned floating balls
- HPC: Fixed ball for goal, sinking ball with changing patterns for other quadrants
- striatum: Same but fix patterns on sinking balls too -> serve as proximal cue

21
Q

How do pool and platform sizes affect MWM performance?

A

Too large pool makes it too difficult (>2m diameter mice can’t learn). Too small makes it too easy, can complete without using spatial cues -> Can find platform by chaining strategy

Small platform sizes makes it difficult. Ratio to pool is important
Usually 120cm to 10cm is good (ie. 140:1)
Training with larger platform and gradually decreasing size can help too

22
Q

What are minimal cues required for rats in MWM?

A

at least 2 distal cues

23
Q

What are the advantages of cued platform training prior to hidden platform trials?

A

Can help identify visual problems
Can help learn/reinforce escaping via platform to avoid thigmotaxis and floating behaviors
-> Do a single day of cued training then with hidden platform trainings

24
Q

How do you carry out hidden platform acquisition trials?

A

Usually 4-8 trial per day, each trial from each cardinal location (NWES)
Can also to equidistant starting locations like NW, N, SE, E, if goal is SW, to smoothen data

25
Q

Why would you run a hidden platform reversal tests?

A

Some mice show intact MWM learning but severe deficits in reversal learning via opposite quadrant platform
Shows cognitive remapping (ie. lesioned HPC makes a behavior inflexible)

26
Q

How long do you have to wait for a probe trial in MWM?

A

At least 24 hrs, below that relies on working memory.

27
Q

How long should a probe trial last in MWM and why?

A

30seconds.
Memory is prone for extinction and mice spend progressively less time in target every 30 seconds

28
Q

How does water temperature affect MWM?

A

Too low or too high impairs performance
Require 20-22C and heating between trials

29
Q

Why is intertrial interval important and how does it affect MWM performance?

A

Helps to enhance learning
Massed practice vs distributed -> Distributed (ie. with 10min ITI) performed better

30
Q

What are sex differences in MWM? In Rats and mice

A

In rats, males tend to perform better in multiple allocentric nav tests
In mice not necessarily true, with male better at RAM and female at MWM

31
Q

How does age affect allocentric learning?

A

Too young, the allocentric network is not developed yet, but egocentric performance is fine as shown by cued navigation MWM. At least in rats

32
Q

Do odor trails affect MWM?

A

No, that is one of the advantages of MWM

33
Q

How does cage enrichments affect performance in MWM?

A

Improves performance with enrichment

34
Q

What are considerations when designing these experiments? How do you take into account those?

A

Blinding (there could be implicit bias),

sample size (too small causes type 1 error of false positives)
- Generally 15-20 is enough but use power analysis to determine

litter effect (littermates are similar to each other but different from other litters in gene, epigenetic, intrauterine environment)
- Best to consider 1 sex pair from 1 litter and could even average data from a single litter -> Prevent oversampling from a single litter

Randomization
- Random assignment of animals into groups