Exam 1 Flashcards
(129 cards)
1
Q
Define Biological Psychiatry
A
Understand metnal disorder in terms of biological function. Everything psych is bio, BUT lifestyle/environment alters biology
2
Q
What does DSM tell us? What does it not?
What tries to fix this problem?
A
Tells symptoms of disorders.
Doesn’t tell you APPROACHES. Also HETEROGENEITY: disorder can look different in different people.
RDoC
3
Q
To diagnose depression, you need / sumptoms including at least 1 of depressed mood and loss of interest/pleasure
A
5/9
4
Q
3 causes of mental illness throughout time
A
- Supernatural
- Somatogenic (bio)
- Psychogenic
5
Q
Who declared mental disorders disorders of the brain?
A
Wilhelm Griesinger (1817-1868)
German neurologist/psychiatrist
6
Q
In first half 20th century, was emphasis more on bio?
A
No, psych with Freud
7
Q
What brought back bio interest in 2nd half 20th century?
A
genetics development. Schizoprenia had genetic component.
Thorazine (Chlorpromazine) marketed in 1954
NEUROCHEMICAL INBALANCE became big explanatory model thanks to drug development
8
Q
When did 1st edition of DSM come out?
A
1952
9
Q
What did the gov declare 90’s to enhance public awareness of brain research?
What journal founded in 1997?
A
Decade of the brain
Molecular psychiatry
10
Q
New findings: effects of psychiatric drugs not primarily exerted via NT in synaptic cleft, BUT
A
Up and down regulation of receptors, effects on intracellular cascades
11
Q
DSM 5 on may 18th 2013, but what was Thomas Insel’s problem 3 weeks earlier?
A
Lacks validity
12
Q
```
If DSM doesn’t have validity, then what is it good for?
A
Clinical utility
13
Q
DSM 5 (2013) to DSM-5-TR (2022)
A
Updated sections. New diagnosis of prolonged grief disorder, 70 modified crieria set, intro and use of manual guides, considers racism/discrimination, New ICD-10_CM codes to monitor suicidal behavior and suicidal self-injury, updated old codes 50 coding updates for substance intoxication and withdrawal and other disorders
14
Q
People only diagnosed with disorder IF
A
Harm to other or self and significant impariment
15
Q
When was homosexuality taken out of the DSM
A
DSM 3
16
Q
The DSM-5, more than other versions, tries to what?
A
Incorporate research findings in classifications
17
Q
Why is DSM 4 anxiety split into 4 categories?
A
Data from neuroscience, imaging, and genetic studies suggests differences in heritability, risk, course, and treatment.
Fear based (phobias)
OCD
trauma (PTSD)
dissociative disorders
18
Q
What is RDoC?
A
Research framework for investigating mental health disorders.
Integration of many levels of information.
Dimensional apporach involving multiple analysis levels
Framework to study mechanisms that cut across traditional diagnostic categories
19
Q
What is required for RDoC to pass for group in internal NIHM workshop?
A
- Persuasive evidence for validity
- Evidence for neural circuit or system that implements the psychological function described
Implicit: linkable to psychiatric clinical phenomenon
20
Q
Similarities and differences of RDoC and HiTOP
A
Similarities: both move away from diagnostic categories. Both work-in-progress approaches.
Differences: how they define dimensions, content and units of analysis, current gaps and limitations.
RDoC reserach framework
HiTop is a dimensional classification system (general p factor)
21
Q
Who made the RDoC? Why?
A
NIMH
Neuroscience has not made major breakthroughs towards prevention and treatment. NO satisfacotry theory of pathophysiology, biology doesn’t map onto DSM
22
Q
Why use the RDoC? How has neuroscience failed?
A
- Heterogeneity (more than 1 way for a symptom)
- measuring biology on different levels is very expensive
- Comorbidity
- Only enroll subjects based on diagnosis
- to understand mental health and illness adopt dimensional conceptualization
- DSM diagnosis aren’t great constructs to begin with
23
Q
Why is PTSD not an anxiety disorder in DSM5?
A
fear/anxiety not central to PTSD
Fear- alarm to present/imminent danger real or perceived
Flashbacks specific to PTSD, low base-rate symptom
24
Q
What symptoms does PTSD share with depression?
A
Anhedonia, difficulty sleeping, irritaiblity, difficulty concentrating
25
Give an example of an experiment using two units of analysis
from the RDoC Matrix (make sure to answer the following
questions in your response): What is your construct of
interest? Who would you recruit into your study? How would
you measure those two units?
Cognitive systems: Congitive control or attention
Populations: ADHD, Autism, NT
Genes, fMRI for circuits, behavior, you can do attention or cognitive control task
26
DSM good for clinical use, increase reliability since DSM 3, good for legal and social systems, clinical phenotypes, but why is it bad for research?
1. Emphasis on reliability over validity
2. Heterogeneity of disorders
3. Extensive co-morbidity (Discrete disorders no symptom overlap)
4. Antedates current knowledge of brain and behavior
5. Difficult to relate diagnoses to genes, particular circuits, or basic behavioral mechanisms
27
Domains of RDoC
1. Negative Valence Systems
2. Positive Valence Systems
3. Cognitive Control Systems
4. Systems for Social Processes
5. Arousal/Modulatory Systems
28
Units of Analysis on the RDoC
Genes, molecules, cells, circuits, physiology, behavior, self-report paradigms
GMCCP B S-R P
29
Negative Valence Systems Constructs
1. Acute threat (fear)
2. Potential threat (anxiety)
3. Sustained threat
4. Loss
5. Frustrative nonreward
30
Positive Valence Systems Constructs
1. Approach motivation
2. Initial responsiveness to reward
3. Sustained responsiveness to reward
4. Reward learning
5. Habit
31
Cognitive Systems Constructs
1. Attention
2. Perception
3. Working Memory
4. Declarative Memory
5. Language Behavior
6. Congitive (effortful) control
32
Systems for Social Processes constructs
1. Affiliation/attachment
2. Social Communication
3. Perception/Understanding of self
4. Perception/Understanding of others
33
Arousal/Modulatory Systems constructs
1. Arousal
2. Biological Rhythms
3. Sleep-wake
34
RDoC Limits
units called behavior and self-report, but at present these units do not intend to include the majority of signs, symptoms, and behaviors requiring clinical attention
many self-report, behavioral, and task exemplars included in the RDoC matrix have inadequate or unclear psychometric properties and were
not developed to operationalize RDoC constructs
limited application in clinical practice
35
HiTop Limits
but do not take into account their underlying underpinnings.
Doesn't include autism or ID
Includes understudied somatoform disorder
36
Anhedonia
No response to reward
37
Complexity of nervous system means there are different ways that
neurotransmission can occur
38
Does RDoC take the 1:1 neuron approach?
No, compels us to understand molecules and
channels within and between two neurons; to assembly of
neurons in circuits; to neural networks; emergent behavior
39
Motor cell will take ____ or more incoming fibers
10,000
40
Chemical synapse transmission
Presynaptic release chemical (NT) pick up by postsynaptic cell
41
Electrical Synaptic Transmission
Gap Junctions
Not synpase, connected with each other.
Direct signal going. Sodium ion, signal that creates AP.
Ions back and forth across neurons
42
Excitatory Synaptic Transmission
Sodium more likely to release AP
Depolarizing next cell, making it less negative
43
Inhibitory Synaptic Transmission
Less likely to fire AP
Make next cell more negative
44
Slow Synaptic Transmission
Metabotropic (postsynaptic cell goes through a lot to open ion channels, time scale difference) Slow.
45
Fast Synaptic Transmission
Ionotropic (NT bind, communication is quick, ions in)
46
Modulatory influences mean that it's not 1:1. Give 1 example.
Dopamine might make it less likely to fire
Make it more negative
47
Nervous system is not linear
Circular.
Posynaptic cell also influences presynaptic cell. All connected one big system.
48
What illustrates complexity of synaptic transmission?
1. Chemical vs. Electrical
2. Excitatory vs. inhibitory
3. slow vs. fast
4. modulation
5. Nervous system not linear
49
Synaptic basics
Calcium through voltage gated ion channels
Vesicles fuse and release NT
50
What concepts reflect complexity and non-linearity?
1. Multiple receptor subtypes
2. Autoreceptors
3. Multiple receptors from numerous inputs converge on 1 target and may interact
4. Erosion of Dale's Law
5. Neuromodulation of synpases and networks
6. INFORMATION PROCESSING BY BRAIN OCCURS ON DIFFERENT TEMPORAL AND SPATIAL
SCALES
7.Feedback loops in the circuit
8. divergence---cells branch extensively to supply many target cells
51
How do autoreceptors increase complexity?
Presynaptic cell releases NT, auto receptor puts it back in cell. Auto receptors on PREsynaptic cell. Regulate how much NT released. Can bring NT back. Monitoring system.
SSRIs use autoreceptors. Block autoreceptors so serotonin can't come back. Stays in synapse for longer period of time.
Mental health meds focus on auto receptors.
52
What 3 principles underlie Erosion of Dales Law?
1. NEURONS CAN RELEASE MULTIPLE NEUROTRANSMITTERS (gaba and glutamate)
2. COHABITATION; CO-RELEASE INFORMATION PRCESSING AND EXPRESSION OF BEHAVIORS IN THE BRAIN IS DISTRIBUTED ACROSS NEURAL NETWORKS (inhibitory and excitatory)
3. SPAN DISTANT SUBCORTICAL-CORTICAL REGIONS
53
Only metabotrophic receptors
Dopamine, Histamine, Norepinephrine
54
Only Ionotrophic
Glycine
55
Give an example of the concept that MULTIPLE RECEPTORS FROM NUMEROUS INPUTS CONVERGE INTO
TARGET AND RECEPTORS MAY INTERACT
1. POST-SYNAPTIC SIGNALS CAN BE AFFECTED BY NUMBER OF NT RELEASE OR SENSITIVITY OF RECEPTORS
2. RANGE OF POST-SYNAPTIC SIGNALS IS A COMPLEX EXPRESSION OF THESE INPUTS
3. For instance, habituation of gill reflex is mediated by less glutamate release at presynaptic cell
56
Erosion of Dale's Law
1. NEURONS CAN RELEASE MULTIPLE NEUROTRANSMITTERS
2.COHABITATION & CO-RELEASE: DIFFERENTIAL RELEASE AS A FUNCTION OF AGE, DRUGS, ETC (CO-RELEASE IS PROCESS BY WHICH 2 OR MORE NT ARE RELEASED BY A SINGLE NEURON IN RESPONSE TO AN AP)
3. FIRING RATE OF AFFERENTS CARRYING MULTIPLE SIGNALS
57
What provides the brain with COMPLEXITY (DEGREES OF FREEDOM) TO MEDIATE COMPLEXITY OF BEHAVIORAL OUTPUT?
Neuromodulation of synapses and networks
58
Broad concept of neuromodulation
variety of substances (small molecule transmitters, biogenic amines, neuropeptides and others) can be released in modes other than classical fast synaptic transmission (such as metabotrophic)
this produces adaptability in behavior
59
Direct effects of neuromodulation
1. Presynaptic modulators target the probability of vesicular release by modifying presynaptic Ca2+ influx, size of the reserve pool, proteins in the active zone
2. Postsynaptically, NT receptor expression and properties can be modulated to change postsynaptic responses independent of NT release.
3. Modulation of NT release can occur through LOCAL FEEDBACK that alters the level of release through retrograde messengers or autoreceptors
4. Neuromodulator release itself can be subject to modulation (nitric oxide (NO) can modify glutamate or serotonin, known as metamodulation)
60
Indirect effects of neuromodulation
Indirect = change excitability of neuron
1. Presynaptic modulation that leads to change in AP shape (e.g., can make it longer)
2. Postsynaptic modulation increases voltage-gated inward currents to enhance excitatory postsynaptic potentials (EPSPs)
(pre AP Shape and post EPSPs through increase voltage gated inward current)
61
Consequence of the complexity of nervous system?
complexity of the nervous system makes it difficult to understand and thus treat mental health disorder because it's harder to study these circuits and how they relate to behavior. It's distributed and not localized.
62
Three findings that have increased degrees of freedom?
1. Multiple receptor subtypes for each NT
2. Autoreceptors: presynaptic cell, regulate amount NT release. Not a direct relationship, effects post synpatic cell
3. Neurons can release mutliple NT (cohabitation- you have multiple NT cohabiting same neuron)
63
Receptors that regulate the pre-synaptic release of NT are
autoreceptors
64
What disorders were moved to their own chapter in the DSM-5 because they didn't fit the old stuff?
PTSD and OCD
65
What is volume NT introduced in 1980s and why did it get noticed?
In some places too many receptors, too few terminals for NT
Strange because active substances must be getting to receptors without release from adjacent terminal
Solution: NT can diffuse to extracellular space and activate receptors from long distances
NTs can be released from dendrites, soma, and axon segments
66
4 types of volume transmission
1. plain old exocytosis (fuse to membrane, release to synapse) (some NT float away)
2. Extrasynaptic exocytosis: ouside of synapse. NT released onto different segment
3. Diffusion through PM
4. Adjaent neuomodulator and glial cell: glutamate release, activtaes ionotrophic Ca2+, NO release
67
Volume vs. Wired Tranmission
**Volume**: nonjunctional complex, transmission privacy limited to **specificty of NT/selectivity** of receptor, one source NT release affects many targets, LONG TRANMISSION DELAY, widespread general effects, effected by agonist drugs, low energy demands
Wired: junctional, transmission privacy presence of tranmission channel for NT at synpase, 1:1 transmission, MINIMAL TRANMISSION DELAY, discrete and essential infomrmation to targets, durgs don't work, higher space and energy costs
68
WHY IT IS IMPORTANT TO APPRECIATE THE
COMPLEXITY OF THE NERVOUS SYSTEM IN MENTAL HEALTH?
1. Understanding of how brain actually works
2. lack of complex understanding means treament failure
- Individual differences in neuronal signaling could cause treament to perform differently in any individual
- 1/3 depressed patients don't respond to any antidepressant
69
DESCRIBE SOME FEATURES OF THE NERVOUS SYSTEM THAT DEMONSTRATE THE COMPLEXITY AND NON-LINEARITY OF THE NERVOUS SYSTEM
1. Multiple receptor substypes for single NT
2. Volume transmission
3. Receptor interaction/cohabitation
4. Metabotropic receptors (Slow release)
5. Co-release different NT (Erosion Dale's Law)
6. Distributed Networks
7. Autoreceptors (presynaptic regulate NT release puts NT beack in cell. Monitoring system)
Electrical = gap junctions
Chemical = NT
70
What are the primary neuromodulatory systems?
Norepinephrine, Dopamine, Serotonin, Acetylcholine, other peptides
Typically act on metabotropic receptors; slower
response than fast acting; however, there are
instances of ionotropic modulation
71
Neuromodultion produces ________________________ of behaviors
adaptability
72
nitric oxide (NO) can modify
glutamate or serotonin, known as....
Metamodulation
This is a direct effect of neuromodulation. Basically, neuormodulation itself can be neuromodulated
73
Not the WAYS neuromodulation happens, but what 2 big things does it change? (The main ones)
1. Synaptic strength and dynamics
2. Neuronal excitability (availability of voltage-gated ion channels)
74
What does Yuste think is partly to blame for our lack of ability to explain behavioral/cognitive states and psychopathology?
The neuron doctrine
75
Unlike the neuron doctrine, what do neural network models assume?
1. Neural circuit function arises from activation of groups (Ensembles) of neurons
2. Ensembles generate emergent functional states that can't indentified by studying one neurons at a time
can't understand mental health from perspective of singal neuron. Identify how individual circuits work and interact with each other over the entire brain to produce psychopathology for a given person
76
According to Yuste, what are some pieces of evidence for distributed circuits?
1. most neural circuits have connectivity matrix of **multiple inputs and outputs**
2. Most excitatory connections are weak (seems as though each neuron is trying to integrate as many excitatory inputs as possible without saturation). In contrast, inhibitory neurons are linked by **gap junctions** as unit
3. **Dendritic spines**: important to maximize different axons/dendrites a cell can connect to. Important for integrating different inputs
Evidence when looking at DMN: areas of the brain fire together correspond to behavior state, but across the brain
77
Single neurons do not mediate beheavior. Rather behaviors rely on the function of....
Distributed networks
78
What is the ability of active substances to travel through extracellular space (non-synaptic) to activate receptors?
Volume Transmission
79
What allows for complex behaviors?
Distributed networks
Alterations in networks involved in mental health disorders
80
Neural networks model assumes emergent properties. What is this?
when you have something distributed across networks and everything works together at different timescales and in different spatial locations, behavior emerges that you might not be able to predict just from individual parts.
Example: DMN vs. task positive network. Might assume opposite state, but fire them together, might not be able to predict behavior.
81
How does memory for our experience happen?
Changing STRENGTH of synpatic connections
82
What refers to the strengthening or weakening of synaptic connections in response to increased or decreased neuronal activation?
Synaptic plasticity
83
Synaptic plasticity differences in time scales
Short term: milliseconds to minutes
Long term: hours, days, years
84
Impairments in synaptic plasticity thought to
contribute to...
neuropsychiatric disorders
85
What are the ways synaptic plasticity occurs?
What NT, Receptors, and ions are involved?
1. Ions: Voltage-Gated Calcium Channels
2. Pair pulse facilitation/depression
3. LTP/LTD
NT: Glutamate
Receptors: NMDA, AMPA
Ions: Calcium, Sodium, Magnesium
86
Ions: Voltage-Gated Calcium Channels
(Synaptic plasticity)
Inflex Ca2+ ions triggers AP by depolarization
AP opens voltage gated calcium channels
The channels get NT released
87
Paired pulse facilitation/depression
(synaptic plasticity)
When two stimuli are delivered in a short interval, the second stimuli can be enhanced or depressed by the first
Depression: inactivation voltage dependent sodium or calcium channels or depletions of ready release vesicles
Facilitation (20-500ms): residual calcium from first AP or activation protein kinases. High probability of NT release, 2nd stimuli likely to depress and vis versa.
88
In LTP, synaptic strenght increases due to
repeated activity
89
In LTD, after long stimuli, what decreases?
Efficacy in neuron synapse
90
Describe short term synpatic plasticity (depression)
(halloween candy thing)
Less likely for NT to be released and have EPSP.
Less likely NT outside synapse to stimuli next cell and have postsynaptic potential in cell.
AP comes down neuron. Calcium channels open, NT released into the synapse. Now second signal comes down (AP), BUT few NT now able to be release (less candy in Halloween bucket). Pretend there is a third, now even less NT available. Now postsynaptic cell probably not going to fire. Not enough NT to stimulate the postsynaptic cell. That is depression. Not enough NT left. Depletion. Depleting cell of NT, cell is depressed. That's short term depression.
How much calcium is there to shut NT off, how much NT is there to stimulate cell? **Paired pulse, not enough NT left, being depleted from pulse. Second pulse, not as much left to stimulate cell.**
91
Describe short term synpatic facilitation
(halloween candy thing)
First pulse goes down. NT is released. 2nd pulse comes at time when a bunch of calcium left in presynaptic cell. **2nd pulse adds more calcium. Addition of previous calcium with new calcium releases a bunch of NT.** That is going to stimulate the postsynaptic cell to make it more likely to polarize. **Mechanism by which facilitation happens is residual calcium**. Calcium still there, then you add to it. Confusing because they are opposite processes.
92
Why sometimes depression sometimes facilitation?
With residual calcium, even if you don't have that much NT left, with so much calcium, release larger % of what is left.
**Depression**, a smaller percentage released because you don't have as much calcium around. 10 NT round 1, 6/10 released, 60% in first AP. Now only 4 left. So for depression, now 2nd AP comes down, you only release maybe 2/remaining 4 or 1/remaining 4, don't have that much calcium.
But **facilitation**, you have calcium and residual calcium and additional, so even only 4 left during 2nd round, calcium means you release larger %. End up with more NT released even though some depletion. These can also happen at the same cell.
**Depression of facilitation depends on probability of NT release, and recent behavior at particular cell. **Ex: Huge AP, depolarized cell and release a ton of NT, probability of release goes down, not a lot left to repackage. But smaller signal, 2nd pulse likely increase probability of release. More NT around release. Determines if depression of facilitation at that time. **What % NT released depends on calcium at that time.**
93
Short term synaptic plasticity:
1. What does it adapt and change?
2. What is it triggered by?
3. Process?
1. Short term adaptations to sensory inputs,
transient changes in behavioral states, short
lasting forms of memory
2. Triggered by short bursts of activity causing
transient accumulation of calcium in presynaptic
nerve terminals
3. Increase in calcium causes changes in probability of NT release by modifying exocytosis
94
Paired pulse facilitiation
2 stimuli delivered within a short interval
Facilitation: **residual calcium** left over from first AP, residual has not yet been uptaken (first action potential releases 10%, second
releases 20%)
95
Paired Pulse Depression
Synaptic depression **decreases the ability of
synapses to release NT vesicles **
2 stimuli delivered within a short interval
Depression: occurs from
1. **inactivation of voltage dependent sodium or calcium channels or
2. transient depletion of pool of vesicles**
First action potential releases 10%, 10 vesicles are
released, 90 left. If have second action potential, 10% of 90 (9) so fewer are released and the amplitude of EPSP is smaller (depletion).
96
Facilitation vs. Depression depends on cell's history of what two things?
Activation and timing
97
Can the same synapse display facilitation or depression?
Yes
98
High P vs. Low P
P = Probability NT release
High P = depression
Low P = Facilitation
99
Example of facilitation:
1. initial signal
2. second signal
3. result
Small inital signal, larger second signal, residual Ca2+
100
Example of depression:
1. initial signal
2. second signal
3. result
Large intial signla, small second signal, depletion of vesicles
101
What is the process that strengthens synaptic connections with frequent activitation and underlies learning and memory by strenghting synaptic connections?
LTP
102
What hippocampus important?
Memory
Subfields classic to study LTP/LTD
Large number of gluatmate receptors in Hippocmpuas
103
What are glutamate's receptors?
NMDA and AMPA
Ionotrophic
104
Glutamate NMDA receptors
blocked by Magnesium
need glutamate binding AND depolarization to open
Magnesium needs + charge in cell to repell out
When open, Na+ and Ca2+ can enter
105
Gluatmate AMPA receptor process
Glutamate taken up, lets in + ions
Let's in sodium
106
Describe the persistence of LTP
Depends on new protein synthesis and transcirption in nucleus of cell
Signaling of nucleus depends on protein kinases (PKA, CaMKIV, Erk-MAPK)
Active transcription factors that promote expression of genes for maintaining synaptic enrichment
ultimately: Structural remodeling
107
What do we mean by structural remodeling in LTP?
growth of new dendritic
spines, enlargement of spines, splitting spines
Structural remodeling: postsynaptic cell. huge response, gene expression happens, growth factors grow more spines. Now even more ways to take NT in and have signal potentiated.
108
Are there other ways to get learning, not just LTP and LTD?
Yes, example: HM and his procedural memories
109
LTD mechanisms
Modest increase in postsynaptic Ca2+ in dendritic spines due to modest NMDAR --> activation of protein phosphatase
Eventually leads to reduction of AMPAR
Longer term maintenance of LTD is being studied, might be releated to dendrite shirnkage
110
Fear in RDoC
Molecules: Glutamate, NMDAR
Cells: neurons
Circuits: Central Nucleus, LatAmygala
Behavior: Freezing
Paradigms: Fear conditioning
111
Fear conditioning in the brain
Associative memory depends on amygdala for induction and maintenance
Thalamus (presynpatic) amygdala recieves inputs (postsynaptic)
Central nuleus important for fear expression
Emotional stimulus --> audiotry thalamus --> laternal nucleus of amygdala to accessory basal and basal to centeral, then to lateral hypothallamus for synpathetic activitaiton.
112
In Fear Conditioning, LTP at sensory input to ________
Fear conditioning induces synpatic potentiaion between thalamic and amygadala inputs into increase what?
Where there are thalamic synapses on lateral amygdala neurons, what happens?
1. Lateral amygdala
2. Synpatic Strength
3. Insertion of new AMPARs
113
Explain the cellular hypothesis of fear conditioning
Happens in lateral amygdala neurons
Glutamate causes depoalrization and opening of NMDAR and AMPA via US (loud noise/shock)
CS (tone sound/animal): EPSP, not enough to open NMDA. Pair CS and US. NMDA removes the magnesium and tons of + ions come rolling in. Some go to the cell nucleus to insert new AMPA receptors, other calcium diffuses to adjacent spines.
Now the EPSP is very big and the NMDA receptor is open. Gluatamte only opened the AMPAs before, but now, more AMPA receptors, so it depolarizes the cell so much that it removes the magnesium so the NMDA recpetors open too.
114
Why is animal research beneficial?
Controlled paradigms; examine circuits
* Patient histories are unclear; circumstances surrounding events are unclear/insufficiently remembered/reported
* Extent of brain damage is unknown
* Generational effects are difficult to control
115
Challenges of Animal Models
Mouse can't speak and model stuff like hallunications or feelings of guilt
Animal model FOR a disorder not OF
Animal models cannot mirror full extent of a given neuropsychiatric disorder
116
Construct Validity of an animal model
To what extent the animal model matches a human diesease?
Construct symptom should overlap in human and animal model (ex: anhedonia)
Similarity between biological dysfunction in human and animal model (ex: neural circuits of reward)
117
Face Validity
Degree of phenomenological similarity between the model and the disorder to modeled
Often just refers to behavioral and congitive aspects of disease, not biological/circuitry
118
Predictive (pharmacological) Validity
Signifies that a model responds to treatments
in a way that predicts the effects of those
treatments in humans
- If SSRIs have a particular effect on depression in humans, should see that same effect in the animal model.
119
Processes we can model reasonably well in animals?
Abnormal social behavior, motivation/reward, working memory, fear, executive functioning, anhedonia, homeostatic symptoms (sleep, appetite, weight, energy), psychomotor retardation/agitation.
120
Processess that we cannot model well in animals?
Hallucinations, delusions, sadness, guilt, worthlessness, suicidality
121
4 Animal model approaches (broadly)
1. Genetics
2. Pharmacological
3. Enviornmental
4. Electical simulation and lesions
122
Name some genetic animal model methods and strengths and weakness
Selective breeding and random mutation and screening (S: phenotypes of interest; W: may produce phenocopy of human disorder)
Transgenic animal (KO, KIN, overexpression) (S: recpaituales genetic abnormallity, focus on gene of interest; W: variable penetrance of genetic abnormality in rodents, human relevance of phenotype may be difficult to establish)
Virally mediated gene delivery to brain (S: Spatial and temporal control over genetic change, focus on gene of interest; W: does not recapitulate genetic cause of human disorder)
123
Describe the pharmacological animal model and it's strengths and weaknesses
Administration of NT agonist or antagonist
S: temporal and some spatial (w/intracranial delivery) control; focus on NT system of interest
W: Lack of evidence that common mental disorders involve selective lesions of a single NT system
124
Describe the Enviornmental animal model and it's strengths and weaknesses
Chronic social stress (adult or during development), chronic physical stress
S: May recapitulate risk factors in humans, easy to administer
W: lack of specificity for a given human disorder, lack of **construct validity** for most human disorder
125
Describe electrical stimulation and lesions animal model and its strengths and weaknesses
1. Brain stimulation, including optogenetic approaches (S: spatial and temporal control over circuit function, may recapitulation some findings in humans with DBS. W: Limits in knowledge of circuit abnormalities in human disorder).
2. Anatomical lesions (S: may produce behavioral abnormalities reminiscent of human disorders; W: lack of evidence for anatomical lesions as cause of human disorder).
126
The process by which synaptic connections become stronger with frequent activiation is known as...
LTP
127
The process by which fewer NT released due to 2 stimuli being delivered within a short interval is known as...
Paired Pulse Depression
128
Name the animal behavioral paradigm thought to be most valid for depression?
Chronic social defeat stress
129
Describe molecular basis of fear conditioning. How do CS and UCS impact neuronal signaling, brain circuits involved, and behavioral correlates.
Brain: Tone (CS) and foot shook (USC) sensory inputs to thalamus. inputs go through thalamus which then inputs to laternal nucleus of amydala. Then we go to the central medial nucleus of amygdala and then behavioral output. Fear conditioning produces potentiation between thalamic and amygdala inputs and increases the synaptic strength
Molecular: paired conditioned stimulus then depolarizaiton in lateral amygdala neuron. Na+ and Ca2+ go to postsynaptic cell and diffuse to another dendritic spine that mediates conditioni stimulus, which changes the strength of inputs and adjacent unconditione stimulus inputs are also highly polarized via diffusion of molecules. After conditioning, greater AMPA receptors on the conditioned stimulus which is thalamic input synapses on later amygdala neurons. Therefore the conditioned stumlus can have the same responses without the UCS.
