BAAM Exam 1

What is an animal model?

A living organism used to study brain-behavior relations with the ultimate goal of gaining insight and making predictions

What are some of the key similarities in humans vs rats?

Bilateral symmetry, hierarchical control, separate systems, and localization of function

Orthologues

Genes that are not quite identical (usually really similar though) but both produce a protein that has the same function.

Genotype

Set of genes in our DNA which is responsible for a particular trait. Describes the makeup of your genes

Phenotype

The physical expressions or characteristics of a genetic trait

Genetic phenotype

Observable physical trait or characteristics derived from the genotype

Behavioral phenotype (endophenotype)

Observable behavioral characteristics/traits (ex: emotional states)

Hallmark symptom

Core symptom to diagnose a disorder. Not all disorders will have one, but if they do, the patient needs to exhibit this in order to meet minimum criteria for diagnosis

Neurobiology of a disorder

Underlying mechanisms of the disorder that causes the behaviors/endophenotypes

Validity

The extent to which a concept, conclusion, or measurement is well-founded and corresponds accurately to the real world.

Face validity

The extent to which the animal behavioral is similar to the analogous human behavior. Symptoms of the disorder are the same

Construct validity

Degree to which the animal model and human function/disorder have the same underlying genetic or cellular mechanism that results in the behaviors. Underlying neurobiology matches

Predictive validity

The extent to which a particular treatment induces the same effect in the animal model as in patients. Are the treatments and affects of those treatments similar?

Ethology

Natural behaviors and capabilities of the animal. When designing behavioral tests/models, you want to take this into consideration and align the tests with behaviors that are ethologically relevant

Reliabilitiy/reproducibility

Extent to which a result can be reproduced consistently when using a given assessment or model. Reliability is within the same lab, reproducibility is from different labs.

Generalizability (external validity)

Extent to which the results can be applied to different populations or species (ex: mouse vs monkey, mouse vs rat)

Age of animal

Important to consider when designing behavioral tests and models because behavior will change with age. Also want to match the timeline of model age to the target population’s age range

What behavioral variability things should be considered when designing or evaluating behavioral animal models?

Environmental factors such as handling procedures, time of day of tests, and experimenters performing the tests should remain consistent. Additionally, behavioral history (naive vs experienced), background strain, sequence of tests, and inclusion of proper controls should also be considered and kept as consistent as possible.

When testing the effects of a drug, which control groups need to be included?

Disorder w/ drug, disorder w/o drug (vehicle), control w/o drug (vehicle), and control w/drug

Stereotaxic surgery

Invasive procedure performed on a live animal to precisely target specific regions of the brain. Stereotaxic instrument is used to hold the animal’s head in place and utilize micromanipulators to precisely measure and target small distances

Brain atlas

Mat of anatomical landmarks in the brain sorted by coordinates used to navigate to specific locations. There are two main starting points: bregma which is where the anterior seams comes together, and lamda which is more posterior (close to where the seams are)

Invasive correlative in vivo techniques

Electrophysiology - measure neural activity to study the electrical properties of neurons

Microdialysis - measure neurochemistry such as the neurotransmitters and proteins involved in a behavior

Non-invasive correlative in vivo techniques

sMRI - uses magnetic fields and water in our bodies to create images

fMRI - measures blood-oxygen-level dependent signal, which is the change in concentration of oxygenated hemoglobin, through blood volume and blood flow

PET scans - uses radio activity of an injected radioactive substance to see areas of activity

EEG - shows activity in certain psychological states (ex: asleep vs awake)

Physical causal in vivo techniques

Lesions - damage or destruction to a specific region of the brain. Many different types

Ablation

Lesion that cuts out the area. Not very much control because you might have to remove other surrounding things

Neurotoxic lesion

Use a drug to lesion, basically killing off neurons in the tissue of interest

Radiofrequency lesions

Use radio waves to lesion a specific area

Pharmacological causal in vivo techniques

Manipulation through administration of various drugs, with a few different ways to deliver the drugs

Intraperitoneal (I.P.) injection

Injection of a substance into the peritoneum, which then must cross the blood-brain barrier. Disadvantage is that you are administering the drug to the whole brain

Intracerebroventricular (I.C.V.) injection

Injection into the lateral ventricles of the brain. Does involve stereotaxic surgery

Local injection

Injection targeted to a discrete brain region. Could involve stereotaxic surgery but not necessarily

Genetic causal in vivo techniques

Manipulate biology in the brain by changing things at the genetic level. If you control the proteins produced by genes through DNA, you can change things on a large scale

Gene

Basic physical and functional unit of heredity. Made up of specific sets of nucleotides (DNA sequences)

Transcription

Process of transcribing (copying) DNA coding sequences (exon) into mRNA

Promoter

Region upstream of gene that contains binding sites for regulating proteins

Transcription factor

Proteins that bind to the promoter to help direct RNA polymerase and regulate the level of gene expression

Transgenic construct

Technique used to genetically manipulate the brain. The transgene along with the necessary regulatory sequences for control of expression are inserted into an animal’s original DNA. Animals that contain this foreign DNA are called transgenic animals

Classic gene targeting

Process of incorporating a DNA construct into a specific locus in an animal’s genome to disrupt or alter endogenous gene function

Homologous recombination

Process of swapping out strands of DNA between two end regions of DNA with identical or similar sequences

Reporter genes

Any gene whose protein product can visually report the location of a particular protein, cell type, or circuit. Examples include fluorescent proteins like GFP which mark the location of a cell

Knockouts

Single gene mutations, inactive expression of a gene

Knockin

Mutate genome to express an entirely different gene

Gross motor functions

Naturally performed motor functions, such as walking. Common assessments include open field and homecage monitoring

Motor coordination & balance

Sensorimotor tests of behavior. Examples of tests include rotorod and footprint pattern

Fine motor functions

Look at small motor movements and skilled motor functions. Examples of tests include nest building and reaching tests

Major endophenotypes of PD

Tremor, rigidity, bradykinesia (slow movements) or akinesia (no movements), and postural disturbances

Disturbances in the brain of people with PD

Dopamine neuron loss in substantia nigra (SN) of basal ganglia

Formation of Lewy Bodies (clumps of protein a-synuclein in pars compacta of the SN)

Treatments for PD

L-dopa : DA precursor so it can become dopamine, pharmacological

DA-agonists: mimic DA effects in brain, pharmacological

deep brain stimulations: used in advanced PD when meds aren’t effective

Declarative (explicit) memory

Things we are largely aware of, can declare them and tell others

Non-declarative (implicity) memory

Info we acquire but don’t necessarily have a memory of learning. Can show actions to prove it’s known rather than just declaring verbally

How did H.M. show principles of memory?

Showed that memory is a distinct and separate ability from other cognitive functions. Showed that MTL (medial temporal lobe) is important for memory. And showed that there are different types of memory

What structures were removed/damaged during H.M.’s surgery?

2/3 of hippocampus, entorhinal cortex, perirhinal cortex, and amygdala

Delayed match to sample task (DMS)

Have an object placed in front of a monkey; if it displaces the object, it gets a reward. Put a curtain down for a minute. Raise it back up and have another additional object (not identical) next to the other one from before; if the monkey can remember the old one, it will move the same object for a reward

Delayed non-match to sample (DNMS)

Same as DMS except want the monkey to displace the DIFFERENT object in the second round, instead of the same object as before

Non-associative learning

Learning that doesn’t require associating or linking stimuli. Can often occur following a single event

Habituation

Reduction in the strength of a response to a stimuli following repeated exposure

Procedural learning

Involves acquiring skills through repeated performance and practice, storing and encoding of motor skills we may have no conscious knowledge of gaining

Parkinson’s patients provide clues that what systems are involved in procedural learning?

Basal ganglia and striatal system

Classical conditioning

Learned association between two stimuli. Associations that typically form between an environmental stimulus and a naturally occurring response

What paradigms are most commonly used to study classical conditioning?

Eyeblink and fear conditioning

Operant (instrumental) conditioning

Learned association between a behavior and a stimulus, where intentional actions have an effect on the surrounding environment (consequence)

Difference between positive stimuli and negative stimuli

Positive stimuli are things that are added, negative stimuli are things that are taken away

Place units (cells)

Cells that fire when an animal is in a particular place

Place field

Location in the environment where specific cells fire

Place learning

Learning the physical position or location of objectives (objects)

Pros and cons of radial arm (olton) maze

Pros: increases spatial demand by having multiple choice arms

Cons: food deprivation needed for motivation, extensive training may be needed, risk of use of olfactory cues

Pros and cons of barnes maze

Pros: no food deprivation needed, no training needed, ethological

Cons: relies on spontaneous exploration, risk of use of olfactory cues

Pros and cons of (morris) water maze

Pros: no food deprivation needed, no training needed, no odor cues present

Cons: can be stress inducing, ethological debate (is swimming actually natural for them?)

Why are flies ideal as a model organism?

Fast generation time/short life span, highly conserved genome, and a numerically simple system (only 8 chromosomes)

What are the 4 stages of a fly’s life cycle?

1. Female flies lay eggs on surfaces, eggs hatch within around 24 hrs

2. Larvae stage - forage and eat for a few days, around 4-5 days

3. Pupa stage - larva encapsulated itself and begins developing wings and legs, takes around 4-6 days

4. Adult emerges and lives for 4-6 weeks

Drosophila Larva Behaviors

1. Mobile but flightless, eating continuously

2. Crawl along surface foraging for food

3. Pulverizing surfaces with a mouthhook and drinking liquid

Drosophila Adult Behaviors

1. Highly mobile

2. Eat sparsely

3. Sexually mature