week 2 - behavioral studies with animals Flashcards

1
Q

Are humans more genetically similar to rodents or cats and dogs?

A

Humans are more similar to rodents than cats and dogs

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2
Q

What is an endophenotype

A

An endophenotype is a measurable, heritable biological or behavioural trait that is intermediate between a genetic cause and a clinical disorder. It is more specific and quantifiable than the broad symptoms of a condition.

Key features:

Associated with a specific disorder (e.g. schizophrenia, depression).

Found in both affected individuals and their unaffected relatives.

Heritable and linked to genetic risk.

More stable and easier to study than complex behavioural symptoms.

Example: In schizophrenia, working memory deficits or abnormal eye-tracking might be considered endophenotypes. Studying them helps bridge the gap between genes and behaviour, improving the development of animal models and targeted treatments.

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3
Q

What is advantages of the endophenotype approach

A

Improves specificity: Focuses on precise, measurable traits rather than broad, variable symptoms.

Bridges genes and behaviour: Helps link genetic risk factors to underlying neural mechanisms.

Enhances animal modelling: Traits like working memory or synaptic plasticity can be reliably modelled in animals, improving translational research.

Increases statistical power: Endophenotypes are often less variable than clinical diagnoses, making them easier to study in genetic or neuroimaging research.

Identifies at-risk individuals: Can be present in unaffected relatives, aiding early detection and prevention strategies.

Facilitates biomarker discovery: May lead to objective markers for diagnosis or treatment response.

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4
Q

pros and cons of zebrafish

A

Pros:

Transparent embryos for easy brain imaging

Fast development and high offspring numbers

Genetically tractable and cost-effective

Useful for high-throughput drug and behaviour screening

Cons:
– Simpler brain than mammals
– Limited complex behaviours
– Some genetic and physiological differences from humans

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5
Q

Why are rodents developmentally useful as a model?

A

They have a quick developmental timescale. They get through childhood, puberty and reach adulthood within 8-10 weeks

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6
Q

What is the immemorial association hypothesis?

A

Hypothesis of why were genetically and behaviorally similar to rodents

Rodents have been associated with us for a very long time

They are commensal organisms because they benefit from living with us - we share the same food

This means they were with us since we transitioned from nomadic hunters into farmers

This means that over hundreds of years we have likely had the same environmental influences on man and mouse

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7
Q

what are some environmental influences that we don’t share with rodents

A

The social environment

They don’t live in a society so this is something we can never properly translate

Psychosocial disorders are hard to model with rodents

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8
Q

Advantages and disadvantages of rats

A

Rat advantages:
* physiology
* anatomy
* behaviour
Rat disadvantages:
* limited genetic diversity
* difficult to manipulate genome

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9
Q
A
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10
Q

Behavior definition

A

Observed animal activity

Activity refers to voluntary or involuntary movements made by conscious, unrestrained animals

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11
Q

Brief history of studying behavior

A

19th Century - Darwin ‘origin of species’ theory of evolution

20th century - Behaviorism, Skinner and pavlov everything can be explained by conditioning

20th century - ethology, looking at innate behaviors of animals in their natural environment

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12
Q

What is anthropomorphism?

A

Anthropomorphism - projecting human qualities onto animals or inanimate objects

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13
Q

How can you measure exploration in rodents?

A

You can measure the innate attraction of rodents to novel objects

Tasks:
-novel object exploration
-holeboard (they stick heads in holes)
- Puzzle box (give them little puzzles to solve to get into their cosy dark enclosed area that they prefer)

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14
Q

What types of cognition can you measure in rodents?

What tasks would you use?

A
  • Spatial and non spatial learning
  • Working memory
  • Reference and recognition memory
    -Attention

Tasks:
- Morris water maze (time taken to find hidden platform)
- 8 arm radial maze
- Social recognition task
- Novel object discrimination
- Two-retractable lever operant chamber (skinner box)
- 5-choice serial reaction time task

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15
Q

What social behaviors can you measure in rodents?

What tasks would you use:

A

Social play behaviour
Social approach
Social hierachy
Aggression

tasks:
- social dominance test
- Social interaction test (males you have to be careful they don’t fight)
- Three chamber social approach task

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16
Q

What communication can you measure in rodents

A

Olfactory communication
Ultrasonic vocalisation
Sonograms

17
Q

describe fear vs. anxiety in rodents:

A

Fear = response to actual threat
Anxiety = response to a potential threat

In fear, rodents may move away from threat

For anxiety, rodents may approach a threat, to investigate it

18
Q

How can you measure anxiety in rodents:

A
  • Open field area (measure how much they avoid being in the open area)
  • Light/dark box (measure how much they spend in the light
  • Conditioning tasks - condition them to associate a stimulus with fear. See how quickly they become conditioned to this response, and how much they learn
19
Q

How can you measure depression in rodents?

A

Focussed on helplesness/behavioural despair (giving up on struggling):

Porsolt swim test - Measure how long it takes before the mouse stops swimming#

Tail suspension test - Measure how long the animal keeps wriggling when suspended from tail

These tests are very sensitive to anti-depressants

20
Q

How would you measure sensorimotor gating in rodents:

A

A loud startling stimulus (called the “pulse”) normally triggers a startle reflex (e.g. a muscle twitch).

If a weaker stimulus (called the “pre-pulse”) is presented just before the pulse — usually 30–500 ms earlier — the startle reflex is reduced.

This reduction is the PPI effect.

Rodents jump off a pressure sensitive grid when startled

21
Q

Why would you look at olfactory behavior in rodents and how would you do it?

A

Olfactory behavior is an important confound for animal behavior in rodents

This is because rodents smell each other to communicate

22
Q

What types of validity do good rodent tasks have:

A

Construct validity - how well the tasks reflects theoretical assumptions

Predictive validity - How well a manipulation predicts performance in the condition being measured

Face validity -Degree of similarity between the responses observed in the task and the disorder it stimulates in humans

23
Q

What are common confounds of rodent tasks

A

Health and physical ability
Sensory ability
Anxiety/stress
Motivation/drive
Locomotor activity
Order of testing
Housing environment
Test environment
Experimental effect

24
Q

how would you measure social behaviour in rodents?

A

The social dominance test measures hierarchy by observing which animal consistently wins access to a resource (e.g., food or territory) over another.

The social interaction test measures sociability by recording how much time an animal spends engaging with another animal compared to being alone.

25
Describe major depressive disorder
common disorder * prevalence ~17% (2♀:1♂) * episodic disorder (chronic & recurrent) * moderate genetic influence (30-40%) * comorbid (anxiety disorders, diabetes, cardiovascular disease) * low mood (irritable mood) * loss of interest or pleasure (anhedonia)
26
Describe the chronic unpredictable stress model of MDD
Chronic (unpredictable) mild stress model (Willner et al, 1992) * repeated exposure to mild stressors * type & number of stressors * duration Pitfalls: * reproducibility across labs poor * strain selection (susceptible strain) * physical & psychosocial stressors
27
Describe the maternal seperation model of MDD
Maternal separation model * separating pups from their mother (Boccia and Pedersen 2001) * pups (day 2-14) repeatedly separated daily for 3 hr * pups (day 9) separated once for 24 hrs * pups v dams from their home cage (Murgatroyd et al, 2009) Pitfalls: * reproducibility across labs poor * strain selection (susceptible strain) * physical & psychosocial stressors
28
Describe olfactory bulbectomy model of Major Depression
Olfactory bulbectomy (Harkin, Kelly & Leonard, 2003) * removal of the olfactory bulbs * limbic-hypothalamic axis * sensory deprivation * hyperactivity in a novel environment; enhanced nocturnal hyperactivity; passive avoidance deficits; deficits in spatial memory * altered monoamine (and other) neurotransmitters * reversed by chronic antidepressant treatment * mechanism poorly understood
29
Describe examples of genetic mouse models of autism
Integrin 3 β3 Lack of preference for social novelty; increased repetitive self-grooming Neuroligin 1 Increased repetitive self-grooming Neuroligin 2 Increased anxiety-like behaviour These are synaptic cell adhesion proteins
30
Describe the maternal immune activation model of mouse autism
Maternal infection (1st trimester) * risk factor for autism in the offspring (Atladottir et al, 2010) * maternal immune activation models (Patterson, 2011): * polyinosine:cytosine [poly(I:C)] * lipopolysaccharide (LPS) * specificity ? (Meyer, Feldon & Dammann, 2011) * deficits in social behaviour and communication, repetitive behaviours, neophobia, anxiety, prepulse inhibition * synaptic changes and microcircuit connectivity
31
Describe the VPA rodent model of autism
Valproic acid (VPA) * elevated risk in offspring of women treated with VPA early in pregnancy (Markram et al, 2007) * single injection of VPA in pregnant rodents (Schneider & Przewlocki, 2005) * reduced expression of neuroligin (Kolozsi et al, 2009) * protective effects of environmental enrichment (Schneider et al, 2006)
32
Describe the advanced paternal age rodent model of autism
* associated with autism and schizophrenia (Janecka et al, 2017) * rodent models using advanced paternal age (Janecka et al, 2015)