Module 3 Systems Neuroscience

Question 1

3 main parts of the somatosensory cortex

Answer 1

touch (tactile), proprioception, nociception (pain)

Question 2

Touch

Answer 2

Driven by cutaneous mechanoreceptors in glabrous and hairy skin.

• Glabrous skin: non-hairy, Merkel cells, Raffini endings, Meissner corpuscles and Pacinian corpuscles
• Hairy skin: clustering of Merkel cells, tactile stimuli through hair follicles. Hair follicles classified based on length and shape
• Receptive fields determined by Meissner and Pacinian corpuscles for small and large receptive fields respectively

Question 3

Proprioception

Answer 3

how we know where out body is in space. Determined by 1a axons wrapped around the muscle spindles and 1b endings in the collagen fibers in the Golgi tendon

Question 4

Nociception (pain)

Answer 4

unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is very subjected modified by lots of different things. Free nerve endings in the epidermis

Question 5

Dual nature of pain

Answer 5

First pain: immediate sharp pain, shorter duration, transmitted through Adelta fibers that are myelinated up to the thalamus then to S1
Second pain: duller, lasts longer unmyelinated C fibers, goes up to the reticular formation , periaqueductal gray, hypothalamus, and central thalamus

Question 6

Dorsal column medial lemniscal pathway

Answer 6

Touch and proprioception

1. sensory axons
2. dorsal column of the spinal cord
3. ipsilaterally up the spinal cord until the dorsal column nuclei (crosses over here)
4. thalamus
5. S1

Question 7

Anterolateral pathway (spinothalamic tract)

Answer 7

Pain and temperature

1. Noxious signals stimulate free nerve endings
2. Crosses at dorsal horn and ascends spinal cord contralaterally
3. 1 Thalamus then S1 (for first/fast pain)
4. 2 Reticular formation, periaqueductal gray, hypothalamus, central thalamus (for second/slow pain)

Question 8

Pain perception brain regions

Answer 8

Affective: how we experience pain and our response to pain

• insular cortex: integrates emotional/cognitive state, emotional processing of pain (both ours and others)
• anterior cingulate cortex: higher activity with people more sensitive to pain
• nucleus accumbens: how we perceive both pain and pleasure
• amygdala: anticipation of pain and perception of pain can influence how we experience pain

Sensory: discriminative about where the pain is coming from

• ventroposterior nucleus (VPN) of the thalamus
• primary somatosensory cortex (S1)

Question 9

Descending modulation

Answer 9

Modulate how long the pain signal lasts and the degree of painful stimulation. Many of the same ascending regions are also involved in the descending regions. Descends onto local inhibitory interneuron that can inhibit the nociceptive receptors and downregulate pain stimulus. Critical for terminating pain stimuli
-Can be influenced by development, personality, culture, etc. to change the way that we perceive pain

Question 10

Temperature

Answer 10

TRP channels that get activated at different temperature thresholds. Uses the same crossing pathway as pain (anterolateral pathway). Noxious temperatures go through pain pathway

Question 11

Neuropathic pain

Answer 11

Damage or lesion to nervous system. Longest axons are the most susceptible to damage. Neurons firing independent of noxious stimulus, get sensation localized to where the damage is. Can occur from changes to the system at any number of locations (nerve endings, cell bodies, dorsal horn, higer order structures or descending modulation) or maladpative plasticity in the PNS (peripheral sensitizations, aberrant sprouting, decreased threshold to stimuli, expansions of receptive fields, increased spontaneuous activity)

Question 12

Allodynia

Answer 12

Experience of pain from normally painless stimuli

Question 13

Hyperalgesia

Answer 13

Exaggerated of heightened response to pain stimuli

Question 14

Spinal cord in movement

Answer 14

All motor activity requires participation of the spinal cord. Extends from the base of the skull to the sacrum, has 31 pairs of spinal nerves originating from the spinal cord to the body. Spinal nerves connect to the spinal cord through dorsal (sensory) or ventral roots (movements)
-Can produce movement independent from the brain

Question 15

Motor neuron

Answer 15

Large nerve cell in ventral horn of spinal cord, drives muscles and movement. Releases acetylcholine onto muscle cell to cause the muscle to contract. Ventral horn=motor neurons

Question 16

Primary motor cortex (M1)

Answer 16

Gives rise to voluntary movement, easiest areas to get a response from by stimulation. Motor cortex has most number of direct connections to the motor neurons. Involved in execution of movements, adapting movements to change, and force and direction of movements

• Brodmann area 4
• each part of the body is represented proportionally by the sensitivity of that area
• organized to use different groups of muscles (not necessarily one specific muscle)

Question 17

Dystonia

Answer 17

Happens frequently in musicians, can’t move fingers separately after years of training. Muscle response to cortical stimulation increased and the muscles respond much more strongly. Can be terated with botox that decreasesanomalous response of muscles

Question 18

Lateral corticospinal tract (pyramidal tract)

Answer 18

M1 major direct pathway. Upper motor neurons cross the midline (just cross don’t synapse) at the pyramid in the brainstem, runs down spinal cord and engages motor neurons in spinal cord. Upper motor neurons are probably these Betz cells in layer 5 of M1.

• 30% of the tract is coming from m1, 30% from S1, and the rest from association areas surrounding M1
• synapse onto inhibitory interneurons

Question 19

Premotor cortex

Answer 19

Medial and lateral area involved in the planning and mental rehearsal and learning movement sequence. Stimulating the premotor cortex leads to the same endpoint so the muscles activated can be different but the end goal is the same

• Medial: internally initiated stimuli
• Lateral: external stimuli and includes mirror neurons. Mirror neurons are the ones that are active while performing a task and while watching someone else perform the task

Question 20

Posterior parietal cortex

Answer 20

Provides sensory information to premotor cortex about environment and informs and activates primary motor cortex

Question 21

Prefrontal association area

Answer 21

Multimodal association area involved in planning of behavior and has major input to the premotor areas

Question 22

Lateral vs. medial motor pathways

Answer 22

Lateral: lateral corticospinal tract , innervates distal muscles and produces fundamental movement

Medial: account for postural adjustments, connect ipsilaterally and innervate proximal muscles.

• vestibulospinal: head and neck balanec
• tectospinal: head and eye coordination

Question 23

Basal ganglia

Answer 23

Not directly connected to cortex but go through thalamus. Direct and indirect pathways that work through dopamine from the substantia nigra onto D1-like receptor expressing cells that produce excitatory response. Dopamine has inhibitory effect on D2 receptors that inhibit the caudate and the putamen.

Tonic inhibtion by basal ganglia is increased with the indirect pathway (D2) and decreased with the direct pathway (D1)

Question 24

Cerebellum

Answer 24

Different lobes have different function, erratic movement toawrds a point. involved in some kinds of motor learning possibly by suppressing incorrect responses but difficult to define action of cerebellum exactly

Question 25

Flexion reflex

Answer 25

Causes contraction of flexor muscle, afferents come in from the skin, connect with interneurons and activate flexor motor neuron. Inhibits the extensor muscle (reciprocal innervation) and produces contraction of flexor muscle on the opposite side to maintain balance (crossed extension component)

Question 26

Knee jerk (deep tendon) reflex

Answer 26

Depends on receptors in the muscle itself, two kinds of receptors: muscle spindle receptors in parallel with muscle fibers and the golgi tendon organ that lies in series with the muscle.
-Activation of muscle spindle produces excitation of motor neurons and contraction of the muscle that the spindle lies in. This is the only monosynaptic connection of the motor neurons in the spinal cord. Golgi tendon acts to inhibit the muscle that the tendon lies in

Question 27

Aberrant reflex responses

Answer 27

testing deep tendon reflex commonly.

• no response=something wrong with motor neuron, spinal nerve, or muscle itself
• Brisk reflex, repetitive, or increased tone=something wrong with connections from brain. motor cortex that is constantly inhibiting the medial motor systems that hold the spinal neurons in check, not inhibting anymore so get increased activity of motor neurons

Question 28

Immune system development

Answer 28

Microglia: generated early in development in the yolk sac with erthrocytes and myeloid cells. Migrate out of the yolk sac into the developing embryo, seed the brain around the same time that the neuroepithelium becomes vascularized and populate the brain within one day and increase through proliferation

Other immune cells switch to hematopoetic location to the fetal liver then after birth the HSCs transfer to the bone marrow and stay there for the rest of your life

Question 29

Monocytes

Answer 29

Two populations that circulate the blood: inflammatory and patrolling.

• inflammatory: look for inflammatory signal, first responders, constantly circulating with chemokine receptors to smell a gradient of activation to the site of ongoing inflammation
• patrolling: intravascular phagocytic cells that crawl on endothelium and take out endothelial cells

Question 30

Microglia

Answer 30

Long-lived, regenerate through proliferation (not infiltration), once they populated the parenchyma they develop territories that don’t overlap where each. Can be activated and become phagocytic. Involved in tissue repair, get rid of debris to allow for axonal sprouting and oligodendrocyte invasion. They continuously monitor their territory by projecting and retracting their processes in the environment. If one microglia is ablated the neighbors will go through the cell cycle to replenish the volume.

Question 31

Microglia-neuron interactions

Answer 31

“eat me”: phagocytosis from TREM2 activation stimulated by phosphatidylserine or glycoproteins

“help”: neuronal injury from purinergic receptor activation from ATP/ADP/UDP
-p2y receptors are g-coupled (extension of processes toward injury, p2y6r important for phagocytosis), p2x receptors are ion channels (activates inflammatory response)

“survival”: microglia survival through activation of csf1r by neuronal il34

“resting”: steady state through activation of cx3cr1 by neuronal cx3cl1 or cd200 on cd200r

“don’t eat me”: neuronal cd47 activation of sirp alpha

Question 32

Microglia pruning of synapses

Answer 32

Thought to be low levels of glutamate that trigger astrocytes to secrete some molecule that upregulates neuronal C1q expression at the weak synapse that then cleaves C3 to C3b that can activate the C3 receptors on microglia to remove the dendrite. Microglia follow chemotactic gradient and move to the place with the highest signal

Question 33

Phagocytosis

Answer 33

inflammatory (microbes) and non-inflammatory (efferocytosis, apoptotic cells). Inflammatory phagocytosis produces pro-inflammatory signaling and tells other cells to come in and help, non-inflammatory phagocytosis upregulates anti-inflammatory signaling like tgfbeta and il10 to coordinate tissue repair.

Phagocytic cells have more proteases, lipases, and the pH goes lower in the phagosome (low pH is good for killing pathogens and chopping up proteins). They can either break things down completely or fuse the small fragments with vesicles with MHC molecules and function as an antigen presenting cell
-the main antigen presenting cells are dendritic cells (don’t have as low of a pH) and they stimulate T cells to react to an antigen

Question 34

Macrophages

Answer 34

Also brain resident but not in the parenchyma, they see the meninges, perivascular space, and choroid plexus (a good highway for immune cells).

Perivascular macrophages are in the perivascular space between the vessels and parenchyma, not present at the capillaries because there is no perivascular space. Perivascular space is connected to the subarachnoid space formed by the space between the vascular basement membrane and the glial basement membrane and at the capillary level they fuse and become one.

Question 35

Innate vs. adaptive immunity

Answer 35

Innate: granules stored inside vesicles that are released when triggered. Fast, non-specific response that aims to limit damage at all costs (proteases, DNases, NO, oxygen radicals). Pattern recognition receptors that aren’t limited one specific signal but a family of signals

Adaptive: T and B cells. two kinds of T cells: cd4 helper T cells that help other immune cells get activated or shut down, cd8 T cells that are effector cell that have nasty stuff that can lyse cells and kill them
-dependent on presentation, slow response because they have to divide, but very specific for their target, can stick around for awhile and help with immunity should the antigen show up again but will diminish over time

Question 36

Brain-immune interactions

Answer 36

Bidirectional communication through autonomic, sympathetic, parasympathetic, and enteric nervous system. Neuro-immune reflex involving sensor, afferent communication, switch, and efferent branch.

• Sympathetic signals usually adrenergic. Stroke or tbi increases sympathetic output that acts on GI tract and spleen and bone marrow to suppress lymphocyte production and increase myeloid blast production from stem cells, switch makeup of peripheral immune system
• Parasympathetic signals usually cholinergic
• Enteric: gut serves as a modifiable immune interface to detect the bacteria we carry around. Can seed the brain and have impact on neurobiology

Question 37

BBB

Answer 37

Made up of the basement membrane and tight junctions. Need BBB disruption for immune cell trafficking in the brain, intact BBB is good barrier against immune cells, and virus, and most pathogens.

Question 38

Immune response timeline

Answer 38

1. Vascular inflammation, vascular endothelial cells react first and provide signal that something is happening.
2. Increased cytokine and chemokine production by cells in parenchyma and endothelial cells, sterile inflammation
3. Activation then infiltration by neutrophils
4. Activation of microglia
5. Invasion by macrophages and lymphocytes

Every cell that goes in can increase damage or help with repair. Can contribute to the damage but also important for tissue repair. without them the outcome is worse
-Also get infiltration of dendritic cells and the anti-inflammatory components that contribute to tissue repair and resolution with IL-10 and TNFbeta that activate regulatory T cells for downregulation of the immune response and secrete BDNF and VEGF

Question 39

Balance of immune response

Answer 39

If inflammation is not resolved immediately you can gets SIRS (system inflammatory response syndrome) that the body will try to counterbalance with CARS (compensatory anti-inflammatory syndrome) that either gets resolved or a cytokine storm. Lots of people die from this overreaction of the immune response, but can also become more susceptible to infections because of the anti-inflammatory response, or again an overreaction of inflammation from all of the neoantigens

Question 40

Addiction

Answer 40

Dysfunction of the reward and motivation system pf the brain. Characterized by a compulsion to seek and take drugs and there’s a switch in behavior after drug use goes from being a reward to a compulsive need. Loss of control for limiting drug intake and immersion of negative emotions and withdrawal symptoms that arise when the drug isn’t available

Question 41

Rewards

Answer 41

Things that act as positive reinforcers for learning, factors that make economic choice, or associated with pleasure and happiness. Dopamine encodes reward salience and critical in decision making and all goal-oriented behavior

Question 42

Operant conditioning

Answer 42

Our behavior is a product of reinforcement in combination with punishment but reinforcement shapes behavior more than punishment. Decision is a choice based on feedback from that action, consider both short and long term consequences

Question 43

Delayed gratification

Answer 43

deficit in delayed rewards in people with addiction, value smaller immediate rewards than larger delayed rewards. Also deficit in punishment processing where behavior is not affected by punishment in addiction

Question 44

Mesolimbic pathway

Answer 44

From VTA dopaminergic projection to NAc shell and core (or ventral striatum) where reward salience is encoded. NAc has medium spiny neurons that are GABAergic that project back to VTA and to the PFC

• Direct pathway: D1 receptors, facilitates reward salience or coding reward to certain behaviors so activation of D1 receptors in neurons in NAc encode pleasurable things. More D1 receptor availability associated with positive learning
• Indirect pathway: D2 receptors help suppress cortical patterns that encode maladaptive or nonrewarding actions, also respond to punishment. More D2 receptor availability associated with negative learning, increases in areas important for compulsion

Question 45

Mesocortical pathway

Answer 45

Dopamine neurons in VTA project to prefrontal cortex, involved with motivation and self-control, working memory, behavioral flexibility. PFC receives DA input and project glutamate back to NAc and VTA. Tonic activity maintains previous rewarding behavior becomes automatic and don’t rely on rewards unless different reward changes it. Phasic activity changes previously learned behavior, burst of D1 receptors makes system plastic and malleable to encode new reward

Question 46

Tonic dopaminergic activity

Answer 46

Dopamine normally has a slow and steady firing rate that’s mediated by GABAergic input onto dopaminergic neuron.
-D2-like receptors inhibitory g-protein and act to decrease activity of post-synaptic cell, also autoreceptors on presynaptic terminal

Question 47

Phasic dopaminergic activity

Answer 47

When reward is present there’s a burst firing with an increased amount of DA in synapse that affects the dopaminergic differentially, after awhile the dopamine starts firing with things that are paired to the reward.
-Pattern of dopamine activity becomes important for coding physical salience, novel salience, and motivational salience

Question 48

Input from other areas to mesolimbic/mesocortical pathway

Answer 48

Excitatory input from prefrontal cortex, hippocampus with memory, and lateral dorsal tegmentum and amgdala

Inhibitory input from nucleus accumbens, ventral pallidum, habenula to DA neurons

Question 49

Cortical hypofunction

Answer 49

Drugs dramatically increase phasic activity to higher level than natural rewards. With repeated use the function in the prefrontal cortex declines,. Hypofunction then D2 receptors are activated and the behavior from phasic activity is cemented and difficult to change

Question 50

Glutamatergic potentiation

Answer 50

Neuronal learning comes from glutamatergic plasticity in neurons through NMDA activation. DA neurons get potentiated where they get much more sensitive to glutamate release coming from PFC. AMPA activation of DA neurons increases with one injection. Fast-acting and long-lasting, potentiation strengthens changes of dopamine receptors

Question 51

Genetic changes in addiction

Answer 51

Dopamine D1 and glutamate AMPA activation causes second messenger events that activate CREB and changes dynorphin gene which decreases sensitivity to drugs and increases negative emotional states during withdrawal (dependence). Methylation of DNA leads to sensitization of drugs and changes to synaptic structure of dendritic spines, like H4 methylation alters synaptic plasticity and increases drug vulenrability to stress. H3 phospho-acetylation increases reinforcing effects of drugs, leads to increased sensitization to drugs themselves and decrease of the reward and compulsive need for the drug. Can be passed to offspring

Question 52

Coma

Answer 52

Unarousable, unresponsiveness from severe brain injuries or pharmacologically induced anesthesia. Anesthesia is fundamentally comatose state. Transient state that you can emerge from
-bilateral lesions to central regions of upper brain stem and reticular formation, pontine reticular formation, and regions in the central thalamus can lead to coma

Question 53

Vegetative state

Answer 53

Coma but the eyes can open and close. Patients can breath and do other autonomic functions, PET shows reduction in metabolic state 50-60%. Associated with loss of thalamic neurons, brainstem preserved. Central regions of the thalamus show more loss of cells with less functioning states

Question 54

Minimally conscious state

Answer 54

Looks very similar to vegetative state but definitive behavioral evidence of self or environmental awareness is demonstrated, very wide spectrum.

• Compared to vegetative state, people in MCS have better outcome in a year’s time. Most people emerge from MCS
• emergence criteria: functional interactive communication or functional use of two objects
• MCS brain is much more integrative, have higher resting metabolism. Metabolism better way to discriminate VS and MCS
• Ambien, through GABAA alpha1 mechanism can produce wakefulness and transition to confusional state so the injured brain can harbor a degree of capacity available through dynamic switch

Question 55

Confusional state

Answer 55

able to speak and interact but some impairment of time, person, or place

Question 56

Locked-in state

Answer 56

Have to have some element of motor fucntion and use this function to determine normal cognition

Question 57

Cognitive motor dissociation

Answer 57

behaviorally patients look like they’re in a coma but don’t have a way to respond to command (no motor). fMRI or EEG to make assessment if functional cognition is present, ask patient to do something like imagine performing a movement and verify that they’re doing this in their head

• graded dissociation and uncertainty about cognition but higher than behavior shows us. Preserve metabolic rate and full electrophysiological architecture of wakefulness including sleep
• -follow commands is one thing, need to be able to have movement to reliably communicate and initiate communication

Question 58

Brain death

Answer 58

death of the brain as an organ. examine by testing face nerves and testing rise in CO2 with loss of ventilation which should trigger brain to breath. Brain itself has no metabolic activity “empty skull”

Question 59

Mesocircuit hypothesis

Answer 59

Multifocal injury across forebrain accumulates to loss of input and death of cells in the thalamus. Central thalamus key role in path to wakefulness by turning down nucleus reticularis and activating thalamic cells. Central thalamus projects to cortical regions and send dominant projection to rostral striatum. These straital neurons have to fire to actively inhibit globus pallidus neurons that inhibit central thalamus.

• Corticostriatalpallidal loop has high threshold up and down states need both glutamate and dopamine as cofactor. Pallidal cells fire continuously and need to be actively inhibited because the pallidum can massively inhibit the thalamus and shut everything down.
• With thalamic neuron loss the front of the brain shuts down first
• Posterior medial complex activation predicts level of consciousness

Question 60

Methods in affective neuroscience

Answer 60

1. Lesion studies (in animals or spontaneous occurring ones in humans)
   - doesn’t account for plasticity, or cell heterogeneity
2. Neuroimaging studies (fMRI-blood oxygenation as proxy for activity, DTI-study white matter architecture, PET-different kinds of NT signaling)
   - fMRI gives whole brain, slower temporal resolution
3. Neural circuit physiology studies (ephys, calcium imaging, and optogenetics)
   - smaller regions, good temporal resolution
   - can manipulate activity

Question 61

Limbic areas

Answer 61

Amygdala: processing fear and fear learning, modify one’s behavior in response to fearful stimuli and processing salience

Ventral hippocampus: involved in anxiety and spatial learning

Hypothalamus: midbrain important for regulating basic drives like appetite, thirst, sex drive, arousal, sleep and wakefulness

Anterior thalamus: relay station

Anterior cingulate cortex: processing reward expectations and expectations about effort required to achieve rewards or avoid fearful stimuli

PFC: regulating behavior responses to emotional stimuli and integrating emotional information to aid in decision making

OFC: reward processing and expectations in combination with basal ganglia and septum

Question 62

Kluver-Bucy syndrome

Answer 62

lesion approach, commonly associated bilateral anterior temporal lobe lesions. Most common features are hyperphagia (eating too much), hypersexuality, hyperorality (tendency to put inappropriate things in their mouth), amnesia, visual agnosia (can’t recognize objects visually), docility, decreased fear

Question 63

Damasio’s somatic marker hypothesis

Answer 63

orbitofrontal cortex is important for decision making. Iowa gambling task: someone with an intact brain learns implicitly that certain card decks are associated with small consistent rewards and others with big risks big rewards.

• Measured autonomic responses and showed sympathetic responses. implicitly learned rules before consciously aware of them.
• -OFC deficits see sympathetic response but conscious awareness isn’t in touch with this so OFC is important for integrating the somatic information and using this to guide behavior

Question 64

Fear conditioning

Answer 64

Cued fear conditioning: Paired conditioned stimulus and unconditioned stimulus with unconditioned response (freezing from foot shock after tone).

• Amygdala gets sensory info and basolateral amygdala integrates the cooccurrence of these stimuli. BLA projects to central amygdala important for mediating behavioral response. CeA intiates behavioral response through projections to hypothalamus (freezing), paraventricular nucleus (endocrine response to stress), and lateral hypothalamus (blood pressure)
• This circuit extremely well-conserved across species, critical for survival to respond and adapt to threats. Behaviors that are conserved aren’t necessarily performed in the exact same way

Contextual conditioning: convergence of different elements associated with fear, harder to learn. Goes through the hippocampus,(so lesion amygdala can still do contextual but not cued, lesion hippocampus can do cued but not contextual)

Extinction learning: can be superimposed on fear conditioning, new form of learning (not forgetting). Infralimbic of the PFC for extinction projects to intercolated cells that inhibit cells in CeA, behavioral response inhibited by ITCs. Prelimbic area for initial learning (lesion prelimbic can do extinction learning but slower to learn conditioning in the first place, lesion infralimbic then can do conditioning but not extinction)

Question 65

Optogenetics

Answer 65

Based on light-sensitive channel proteins. Channel rhodopsin gets exposed to light causes conformational channel and increases sodium conductance, causes depolarization. Halorhodopsin conducts chloride into the cell to inhibit it. More specific than electrical stimulation, allow for control over what neurons you’re driving.
-Can dissect functional heterogeneity in the circuits. BLA neurons that project to either central amygdala (fear learning) or nucleus accumbens (reward learning)

Question 66

Research domain criteria project (RDoC)

Answer 66

systematic way to link different domains. negative symptoms, positive symptoms, cognitive impairments and cognitive symptoms, social processing, and arousal/regulatory systems.

• How we categorize animal behaviors that we use into these various domains.
• Many symptoms seen across various disorders are overlapping

Question 67

Cognitive function domain

Answer 67

Most common is learning and memory like novel object test (test both learning and memory), Morris water maze (spatial memory), can use fear as a memory test, cognitive flexibility (how well an animal can move from one test to another–animal model of autism) fear extinction and y-water maze, anxiety is one of the most commonly used behaviors

Question 68

Mood and cognition domain

Answer 68

Common with depression and anhedonia. forced swim test, tail suspension test, sucrose preference (also has a reward component)

Question 69

Social domain

Answer 69

social communication–ultrasonic detectors to record ultrasonic vocalization between animals and test whether they’re communicating or not

Question 70

Criteria of validity

Answer 70

1. Face validity: use behavioral test to study phenotype that is seen, develop test that reproduces human condition
   - use as many tests as possible to validate the data seen in one
2. Construct validity: genes that are linked to a particular disease, have construct of biological cause that you’re trying to understand if it does drive behaviors seen in the human condition
   - have prior knowledge of where gene of interest may be important and use particular test based on that
3. Predictive validity: using behavioral phenotype for treatment to see if it can predict outcome in patients (does it relieve motor deficits?)

Question 71

Open field test

Answer 71

Allowed to roam within the box, center of the box is anxiogenic, more anxious=less time in the center. Optogenetic activation of BLA>vHPC make more anxious

Question 72

Elevated-plus maze

Answer 72

used quite a lot, more anxiogenic than open field. measure time on open arm as readout anxiety-like behavior

Question 73

3 chamber social behavior test

Answer 73

one side has cup with stranger, the other cup has some object. most mice are curious and social so they spend more time with the stranger mouse than object. measure time in social zone or time interacting

Question 74

Water Y-maze

Answer 74

equal sized, put in one entrance and trained to find platform because mice don’t like water. Measure the latency (time to find platform), recruits hippocampus, prefrontal and striatal components

Question 75

Morris water maze

Answer 75

find platform in open water. most classically used for spatial memory, recruits hippocampus

Question 76

Light/dark chamber

Answer 76

another anxiety test, bright light is anxiogenic, measure time spent in each chamber

Question 77

Motor tests

Answer 77

measure rearing and distance traveled. rotarod.