Lecture 2 - RM in cognitive and biological psychology

Question 1

animal research

Answer 1

• any research involving animals. 2 areas:
  1. licensed work - all activity covered by scientific procedures act. most lab based
  2. unlicensed work - observational e.g. zoo, wild

Question 2

alternatives to animal research in neuroscience

Answer 2

• brain organoids (+ = indiv brain areas, dev research. - = no natural shaping through stimuli, no blood vessels immune system, no interaction with organs)
• computer models (+ generate ideas, predict testable outcomes, - build by humans, may be unknown)
• human exp (+ complex paradigms, non invasive techniques - lacking detailed resolution, mostly observational)

Question 3

what are animals used for in research

Answer 3

• basic research/discovery science
• applied research e.g. development of medicines, treatment & legal requirement to be tested on 2 species of mammal
• regulatory testing - procedures to satisfy legal requirements.
• breeding of genetically altered animals e.g. discover gene functions, can remove or add genes to mimic diseases in humans

Question 4

choosing correct animal

Answer 4

• controversial but has advanced medicines, techniques & scientific understanding
• special protected species require special reasons with less than 0.1% research being on them. 97% on mice, rat, fish or chicken

Question 5

animal scientific procedures act UK

Answer 5

• defines a procedure more than injection to a protected animal for experimental or scientific purpose that may cause sufferring or distress
• total procedures dec slightly
• most species are mice fish & rats (zebrafish for genetics)
• half of animal research is for basic research, mostly looking at nervous system, immune system, oncology then multisystemic and cardiovascular

Question 6

experimental procedures by severity

Answer 6

• sub threshold - authorised under project license but no sufferring above threshold of regulation. less than pain of a needle.
• non recoveru (under GA) - entire procedure done under GA from which they shall not gain consciousness.
• mild - pain at worst only minor so can return to normal state in short time. 46% mild
• moderate - procedure caused signif & detectable disturbance to normal state but not life threatening. 27% moderate.
• severe - procedure caused major change from normal state and inc long term disease process or persistent deficits. could cause death 3.6% severe.

Question 7

context of animal use beyond research

Answer 7

• 2022 2.7m prcoedures performed on live animals mostly rodents & fish
• uk meat and fish eaters consume 2.2b animals every year. 1.2b land.
• 9m cats and dogs have poor welfare
• 15m wild birds shot every year and 20m rats and mice killed as pests
• cats kill 160-270m animals annually. 100x that used in research

Question 8

advocates for animal research

Answer 8

• human life = greater value
• legislation protects against cruelty
• millions animals killed as pests etc
• few animals experience pain and killed before sufferring

Question 9

opposition to animal research

Answer 9

• animals should have same rights
• strict controls do not prevent all sufferring
• research does not translate well to humans
• deaths are unnecessary
• how do you know when they feel pain
• poor design/invalid science

Question 10

origins of animal experiments

Answer 10

• aristotle - animals may have feelings but no reason
• galen - dissected animals and chartered cardiovascular system
• descartes - believed animals did not have moral rights. suggested animals cannot suffer as have no mind or soul and were a machine.
• darwin - believe we are only different degrees as animals on same evolutionary steps
• in 1700-1800s power to people inc where people became better educated, informed and fighting power systems
• legislation put in place e.g. cruelty to animals act 1876

Question 11

cruelty to animals act 1876

Answer 11

• first legislation to protect animals and control research in world unique for 50y
• lasted until current ASPA

Question 12

3Rs (Russell & Burch)

Answer 12

• replacement - replace using alt technique without animals
• reduction - min use of animals to min number
• refinement - minimise suffering in method e.g. better housing and conditions

Question 13

why protect animals

Answer 13

• ethical
• stressed animals do not give reliable results
• 1970s public outcry
• complaints over unnecessary nature of research
• consequences of scientific procedures act

Question 14

animals scientific procedures act 1986

Answer 14

• protected animals = all living vertebrae excluding man inc cephalopods
• personal: authority ti perform procedures
• project: authority for programme of work
• place/establishment: authority for premises where taking place
• legal obligation of 3Rs to protect animals under scientific purposes.
• need evidence you have considered 3Rs.

Question 15

how animals are used in research 1: animal model of memory

Answer 15

• HM head trauma. minor epileptic seizures. at 27 had hipp removed on both sides
• could learn sensorimotor skills but impaired spatial memory

Question 16

how animals are used in research 1: cognitive map of space

Answer 16

• rats could map novel route without practice (Tolman)
• knowledge can be based on cog maps
• learning something like a field map of environ which serve wider cog functions beyond space and navigation
• assessed using mwm
• poulter et al (2019) - hipp lesion and control group. homologous region of hipp in mammals - very susceptible to aging and disease
• simpler system suggested by Herculano-housel 2009 - higher neuron numbers in human hipp.
• Hill & walsh 2005 - more cortical layers in humans but actual cells not different. function and structure preserved

Question 17

how animals are used in research 1: in-vivo extracellular single cell electrophysiology in mice

Answer 17

• mice single cell recording found brains positioning system discovering place cells in hipp (o keefe)
• recorded neuronal spiking patterns
• place cells for tolman’s cog map?
• Lever et al (2002) - different cells become active in different places = place cells context specific.
• kentros et al (1998) - cog maps are learned and stored. when blocking learning a new map will be made the next day.
• wills lever et al 2005 - place cells can pattern complete. seeing part of familiar place will subcomplete pattern of a familiar location and fire some place cells e.g. linsk to crime scenes

Question 18

how animals are used in research 1: future of rodent memory research

Answer 18

• 2d VR can instantaneously add subtract or warp sensory input & eliminate odours
• can use large microscope to image deep brain regions & see indiv neuron communication

Question 19

how animals are used in research 2: alzheimers

Answer 19

• alzheimers characterised by presence of 2 neurotoxic proteins:
  > Amyloid-β plaques (extracellular space)
  > Tau tangles
• difficult to study while alive in humans
• transgenic mice models can be created to overexpress genes in alzheimers. show they develop hallmarks as they age e.g. Amyloid-β plaques, Tau tangles (or both in hybrids) & Memory impairments
• in transgenic alzheimer mice it was shown amygloid-b plaques burden cor with memory impairment
• chen et al (2000) - showed amyloid-b plaques cor with memory impairment and these form in hipp. also shown animals forget things as they age = pave way for drug testing on memory impairments

Question 20

How animals are used in research III: Brain circuit manipulations - Understanding the brain circuits of memory using genetic tricks in mice

Answer 20

• 75% of the first 312 DNA exonerations in US were victims of faulty eyewitness testimony
• found hipp involved in recall of false and genuine memories (Cabeza et al 2001)
• optogenetics - borrowing phosensitive molecules and insert in neurons of interest - shining light then turning these neurons on/off. helps control indiv types of neurons. inserting light sensitive switches into specific types of cells (ramirez et al 2013)

Question 21

How animals are used in research III: Brain circuit manipulations - using genetics to temporarily activate or inhibit a specific population of neurons

Answer 21

• optogenetics - using genetically engineered mice and pulses of light to control the activity of neurons
• chemogenetics - allows for the reversible control of neuronal populations using genetically engineered receptors
• optogenetics and chemogenetics confer an adv over older lesion methods since you can temporarily control neuronal activity after which normal function is typically restored
• can help target neurons
• applied usefulness in ptsd: people cannnot suppress memory and maybe these methods can target these cells and switch them off - currently not allowed due to ethics

Question 22

advantages of using animals

Answer 22

• can be more invasive
• quick reproduction cycles in rats
• can study whole life cycle
• used to validate other types of research
• can manipulate brain and genes
• some similar circuits to humans
• crucial for understanding diseases e.g. alzheimers
• develop and test new drugs
• contributed to 70% nobel prizes for physiology & medicine
• complex brain networks underlying cognition cannot be tested in petri dish
• can study manipulation on behaviour

Question 23

disadvantages of using animals

Answer 23

• physiological differences
• humans can react differently to drugs
• animal care and housing can be costly and resource intensive
• many items tested are never used on humans
• many null results
• genetic variability
• distresses animals
• can waste animals
• some products harmful to animals are useful to humans e.g. insulin
• unnatural lab
• harder to target specific brain regions