Lecture 6: Amygdala, Fear and Emotion Flashcards
(110 cards)
1
Q
Emotions are mechanisms for _
A
adaptation
2
Q
What can promote adaptation during important life events?
Emotion
A
Short lived biopsychosocial phenomenon
- Activate biological and physiological systems
- Promote action via a motivational state of personal significance
- Express to others how we interpret our present situation
3
Q
When are emotions Adaptive?
A
when they prioritize behaviors that optimize adjustment to ongoing demands
- Fear of being bitten by experimental animals motivates a graduate student to take a firm grip when scruffing a mouse, exerting control
4
Q
When are emotions Maladaptive?
A
When emotions prioritize behaviors that interfere with effective adaptations, they are maladaptive
- Fear of being bitten by experimental animals motivates the graduate student to allow volunteers “the opportunity to learn to handle mice.
5
Q
What are two ways we can resolve an issue (emotions)?
A
Maladaptive or adaptive behaviors
- Adaptive if they optimize adjustment to ongoing demand.
- Maladaptive if emotions interfere with effective adaptations.
6
Q
Explain the difference between emotions vs. moods
A
- Emotions: Short-lived biopsychosocial phenomenon that can promote adaptation (ex. fear)
- Moods: consist of persistent biases that prepare the organism for emotional events. (ex. anxiety)
7
Q
T/F: Anxiety is an emotion
A
False, it is a mood-> persisent state that biases your thought processes
8
Q
Fear an emotion or mood?
A
Fear is an emotion
9
Q
What is fear?
A
- Consists of physiological changes for action (fight or flight)
- Fight or Flight
- Short lived
10
Q
What is anxiety?
A
- Moods consist of biases that prepare the organism for emotional events.
- Persistent
- Anxiety consists of sustained arousal, vigilance and apprehension of vague, potential threats.
11
Q
How is anxiety (mood) adaptive or maladaptive?
A
-
Adaptive to the extent that the mood promotes conditions that enhance functional responses to emotional events.
- If mood enhances functional responses to emotional events
-
Maladaptive to the extent that the mood interferes with day-to-day functioning and/or contributes to dysfunctional responses to emotional events.
- If mood interferes with day/day functioning
12
Q
The circuits mediating fear overlap considerably with those mediating _
A
anxiety
13
Q
Posttraumatic stress disorder (PTSD) and Anxiety disorders affect approximately _% of US adults each year
A
18%
14
Q
What are some Anxiety disorders?
A
- Panic disorder
- Generalized Anxiety Disorder
- Social Anxiety Disorder
- Phobias
15
Q
Posttraumatic stress disorder (PTSD) and Anxiety disorders are characterized by what?
A
By a dysregulated fear/anxiety response
- The response is disproportionate to the event and produces maladaptive behavior
- Overgeneralized response that occurs outside of situations should be expected to occur and produces maladaptive behavior.
16
Q
What is the most common symptom of anxiety disorder?
A
Overgeneralized fear/anxiety
- The response occurs outside of situations it should be expected to occur and produces maladaptive behavior.
17
Q
What is important to understand and treat anxiety disorders?
A
Understanding the neurocircuitry that mediates the experience, expression and learning of fear and anxiety
18
Q
Who and what first proposed that specific brain circuits are devoted to emotional experience and expression?
A
James Papez and Broca’s Limbic Lobe
- Emotional system on the medial wall of the brain linking cortex with the hypothalamus
- Cortex forming a ring around corpus callosum: Cingulate gyrus, medial surface temporal lobe, hippocampus
19
Q
Emotions are found in one or many brain regions?
A
many brain regions, not a fixed state
- state of constant flux as a consequence of interactions between multiple brain regions
20
Q
What is the septum/septal area responsible for? What happens when you lesion the septum?
A
- Responsible for temperance/regulation of emotional responses
- Disinhibit the hypothalamus which results in extremes of emotion, including explosive violence
21
Q
What regions are involved in emotion/mood? And what they are responsible for?
A
Broca’s Limbic Lobe
-
Thalamus: Responsible for processing sensory
inputs - Cingulate Gyrus: Responsible for emotional experience.
- Hippocampus: Responsible for understanding the context of the experience.
- Hypothalamus: Responsible for emotional expression
- Neocortex: Responsible for emotional coloring
22
Q
What happens when a temporal lobectomy happens? What is a syndrome with this? What area is also affected?
A
Because you probably cut the amygdala as well
- Decreased fear and aggression
- Decreased vocalizations and facial expressions
Probably related to the destruction of the amygdala
- Klüver-Bucy Syndrome
- Amygdala
23
Q
What is Klüver-Bucy Syndrome?
A
A very rare cerebral neurological disorder associated with damage to both temporal lobes resulting in abnormalities in memory, social and sexual functioning and idiosyncratic behaviors
24
Q
What happens in animals with bilateral amygdalectomy?
A
- Reduces fear and aggression
- Anger, sadness, and disgust also affected
- Inability to recognize fear in facial expressions
- S.M. case study: Inability to recognize fear in facial expressions
similar to the temporal lobe
25
What happens when we stimulate the amygdala
Increased vigilance or attention
26
Fearful faces produce greater _ activity than
happy/neutral faces
**Amygdala** which shows that the amygdala is involved in some kind of assessment of emotional states
27
What are all the structures involved in fear?
**Amygdala**
* Baso-lateral Amygdala (BLA)-> Lateral Amygdala (LA), Basal Amygdala (B), Accessory-Basal Amygdala (AB)
* Central Nucleus (CEA)->Lateral (CEl) andMedial (CEm)
**Intercalated Cells (ITC)**
**Extended Amygdala**
* Bed Nucleus of the Stria Terminalis
(BNST)
* Medial Extended Amygdala (MEA)
**Hypothalamus**
* Releases regulatory hormones->e.g. corticotropin-releasing hormone
28
What are the different areas of the amygdala?
**Baso-lateral Amygdala (BLA)**
* Lateral Amygdala (LA)
* Basal Amygdala (B)
* Accessory-Basal Amygdala (AB)
**Central Nucleus (CEA)**
* Lateral (CEl)
* Medial (CEm)
29
What are intercalated cells (ITC) involved in mediating?
Extinction
30
Extended amygdala recieve projections from where?
basal later amygdala+ central nucleus
31
The _ is a substrate for learning fear
Amygdala
32
How do the amygdala and associated brain circuits receive inputs?
* The amygdala receives input from several sources and projects to regions that mediate physiological and behavioral responses.
* With experience, the amygdala changes how it responds to sensory inputs that are paired with aversive stimuli.
33
When is fear conditioning used?
study the role of various brain regions in the manifestation of fear
* Cue elicited
* Contextual
34
How does fear conditioning work?
* Unconditioned Stimulus (ex. Shock)→Unconditioned Response (ex. fear)
* Neutral Stimuli (Cue or Context) + US (ex. Shock) → UR (ex.fear)
Then:
* Conditioned Stimuli (Cue or Context) →Conditioned Response (ex. Freezing)
35
How can fear conditioning be established?
Fear conditioning can be established in a single CS-US pairing; can be established to both a cue and a context; is difficult to extinguish; and can be recovered if extinguished.
36
Explain what is going on with extinction in the different phases
* **Extinction of fear conditioning is often context dependent**. If previous context is reintroduced (i.e. placing mouse in green/purple room), the conditioned fear response will still be present.
* In other words, mammals have an innate ability to distinguish safe from unsafe spaces. During fear/anxiety disorders, the ability to distinguish between safe and unsafe spaces in impaired.
37
What NTs and modulators are released during fear and how does that contribute to learning?
* Fear-inducing stimuli activate stress hormones (CRF, ACTH, cortisol) and neurotransmitter (Glu, NE, ACh, DA) release
* These neuromodulators can facilitate learning and strengthen associations
38
Explain the function and action of Glutamate released during fear
| NTs
* **Expression→Primary transmitter during expression**
* **Consolidation & Extinction→NMDA/AMPA mediated LTP for both consolidation and extinction**
39
Explain the function and action of GABA released during fear
| NTs
* **Expression→Tightly regulates fear expression**
40
Explain the function and action of Glucortiocids released during fear
| Hormones (CRF, ACTH,cortisol)
* **Experience**→↑ physiological arousal/energy utlization
41
Explain the function and action of Epinephrine released during fear
| NTs
* **Experience**→↑ physiological arousal
42
Explain the function and action of Norepinephrine released during fear
| NTs
* **Consolidation**→↑ by β agonist
* **Extinction**→↓ by β antagonist in IL ctx
43
Explain the function and action of Dopamine released during fear
| NTs
* **Consolidation**→ ↑ by D2 agonist in VTA
* **Extinction**→↓ by D1 antagonist in IL ctx
44
Explain the function and action of Acetylcholine released during fear
| NTs
* **Consolidation**→ ↑ by nACh agonist in Hcc, ↓ by ⍺7 nACh antagonist
* **Extinction**→ ↓ by nACh agonist
45
What does the basolateral complex consist of?
the lateral (LA), basal (B) and accessory-basal (AB) nuclei of the amygdala
46
Lateral (LA) neurons are responsive to what stimuli? and receive what stimuli?
* Responsive to painful stimuli
* Receive auditory inputs and visual inputs
47
Lesions of the lateral amygdala (LA) impair what response? ⭐️
| Part of the Basolateral complex
Impair emotional responding to shock
48
Lesions of the LA impair what types of conditioning? ⭐️
| Part of the Basolateral complex
cued and contextual fear conditioning
49
Lesions of Basal and accessory-basal of the basolateral complex has what effect?
have no effect on fear conditioning, indicating that the LA is critical.
50
What exists within the LA?
A substrate for learning to be afraid (CS->US pairing) exists within the LA
51
During fear conditioning, what is the properties of the LA neurons? why?
* LA neurons fire sooner than before they started learning
* LA neurons fire more frequently
* These activity changes are in response to input from the thalamus, not the sensory cortex
* These activity changes are in response to **LTP (Consolidation –
Glutamate) between the LA and thalamus, NOT the sensory cortex**
52
Explain this graph
Faster than normal pathway (see picture) so conditioning is bypassing the cortex (conscious process). **This proves that fear is a subcortical process so you are not thinking**
53
Cue elicited fear is mediated by what?
by strengthening of thalamus->LA
| look back on slide 18
54
Basal and Accessory Basal Amygdala recieves projections from where?
Receives projections from CA1 and the subiculum of the hippocampal formation (HF).
55
What are the two distinct excitatory cell populations of the basal and accessory basal amygdala?
* Anterior "Aversion" neurons
* Posterior "Reward" neurons
56
Anterior “Aversion” neurons:
1. Expresses?
2. Respond to?
3. Reciprocal connection with? ⭐️
4. Inhibitory interneurons connections with?
1. express R-spondin 2(Rspo2*)
2. Respond to negative valance stimuli
3. **Reciprocal connections with PL (paralympic cortex in PFC) cortex** ⭐️
4. **Inhibitory interneuron connections with posterior BA neurons**
57
Posterior “Reward” neurons:
1. Expresses?
2. Respond to?
3. Reciprocal connection with? ⭐️
4. Inhibitory interneurons connections with?
1. Express protein phosphatase 1-regulatory inhibitor subunit 1B (Ppp1r1b*)
2. Respond to positive valence stimuli
3. **Reciprocal connections with IL (infralimbic cortex) cortex** ⭐️
4. **Inhibitory interneuron connections with anterior BA neurons**
58
What are posterior and anterior BA neurons doing?
competing with each other for bad vs good
59
Extinction of fear is associated with what? ⭐️
increased inhibition of anterior neurons and decreased inhibition of posterior neurons
60
Lesions of the hippocampal formation have NO effect on what emotion?⭐️
have no effect on emotional responding to shock
61
Lesions of the hippocampal formation impair the ability to do what? ⭐️
learn to fear the context, but not the cue associated with shock
62
Hippcocampus (HCC) with basal accessory amygdala mediates what? What hapens when you have inactivation of HCC?
* The hippocampus (Hcc), in conjunction with the amygdala, mediate context dependent extinction of cue elicited fear.
* Inactivation of the Hcc impairs the retrieval of CS-Context associations (overgeneralization)
63
A fear-inducing CS will produce fear in any new context. However, repeated CS exposure in a context without a US will lead to what?
Extinction in that context
* Extinction is context specific
64
What does the hippocampus mediates?
context dependent extinction of cue elicited fear, i.e. when not to be afraid.
65
Inactivation of the hippocampus impairs what?
impairs the retrieval of CS-Context associations
* Results in a failure to distinguish between CSs presented in different contexts, i.e. overgeneralization.
66
* What is involved in context dependent expression of fear?
* What is involved in suppressing fear reponses following extinction? ⭐️
* Hippocampus->BLA and Hcc->**PL**->BLA are involved in context dependent **expression of fear**
* Hippocampus->**IL**->CEA involved in suppressing fear responses following **extinction**
67
explain this
* If the PL cortex is optimally activated you get activation of the basal lateral amygdala . Which sends projections to central nucleus which will illicit a fear response
* If the IL cortex is activated it activates interpolated cells which are GABAnergic neurons which sends projections to central nucleus→Inhibitory
68
What are the central nucleus subregions?
Lateral central nucelus (CEI) and medial central nucleus (CEm)
69
The lateral central nucleus (CEl) is similar to what? How does it work?
Similar to LA
* NMDA antagonism blocks the acquisition of fear conditioning
* preventing protein synthesis blocks consolidation
70
Hippocampus (Hcc) and Ctx inputs are also involved in what?
context mediated extinction of cue elicited fear
71
medial Central Nucleus (CEm) is for what?
Primary output for behavioral responding (expression or lack thereof)
72
Explain fear conditioning and fear extinction with the central nucelus
GABAergic neurons are involved in the inhibition of amygdala outputs and the extinction of fear mediated by glutamatergic inputs from the hippocampus.
73
The central nucleus (CEA) of the amygdala receives input from what? What does it mediate?
* the lateral, basal and accessory basal amygdala
* positioned to mediate both cued and contextual expression of fear.
74
* Central nucleus (CEA) of the amygdala is interface with what?
* Damage to the CE interferes with what?
The CEA is the interface with motor systems and damage to the CE interferes **with the expression of conditioned fear responses.**
75
Damage to CEA projection areas leads to what?
to selective loss of responses
– i.e., damage CEm->lateral hypothalamus, affects blood pressure but not freezing or hormone release
76
lateral amygdala:
Central amygdala:
* lateral: experience of fear
* Central: expressing of fear-> can lesion and will still be fearful but will not have an external response
77
What is the CEm?
## Footnote
CEm: Medial Central Nucleus
excutor of fear reponse by controlling all brain regions that produce fear reponses
78
What are all the different areas that the CEm targets with the fear symptoms?
79
The amygdala receives what type of information
The amygdala receives sensory, contextual, and regulatory information.
* Poised to use information about threat, context, and internal states to initiate defensive responses.
80
What connects to the bed nucleus of the stria terminalis?
Both the basolateral (BL) and central nucleus (CE)
81
What happens when there is prolong activation of the (basolateral) amygdala?
* **suppression of the medial central nucelus** (major output) which is portion of brain that is involved in activating your fear response so instead **you get activation of bed nuc. of stria term** (which is extended amygdala)
* The release of corticotropin releasing factor (CRF) onto the BNST produces a heightened state of arousal and vigilance (anxiety).
82
Optigenetic stimulation of the baso-lateral amygdala produces what?
anxious behavior
83
What is released in the BNST? What does it produce?
## Footnote
BNST (Bed Nucleus Stria Terminalis) part of the extended amygdala
Corticotropin-releasing factor (CRF) released in the BNST produces a
heightened state (increase sensitivity) of arousal and vigilance
* sensitizes startle responses to US
* facilitates responding to diffuse cues-> long duration cues and contexts
84
What is the most common comorbidity with anxiety disorders and PTSD
Major depressive disorder
85
What was shown in behavioral depression in rat models?
learned helplessness
* Results in a passive coping behavior (inhibited CEm)-> response to stress by doing nothing
86
behavioral depression in rat models caused by what? Characteristics?
Caused by chronic exposure to unpredictable aversive events
* Elevates circulating CRF
* Desensitizes 5-HT receptors in BLA and mPFC
87
What attenuate anxious behavior?
SSRIs-> start to engage in behaviors to deal with anxiety
88
What is the 3 sympotom clusters in PTSD?
* Re-experiencing trauma through intrusive thoughts, nightmares, flashbacks
* Avoidance of reminders and social situations; emotional detachment-> maladaptive behavior
* Exaggerated startle, hypervigilance in response to trauma related stimuli-> like anxiety
| decrease in central nucleus and increase in BNST activity
89
What is increased and decreased in PTSD?
* lateral amygdala working overtime to learn and strendthen fear (over consolidation) and increase in BNST activity
* decrease in hippocampus +PFC and activity of the CE
90
PTSD is associated with?
Individuals suffering from PTSD exhibit difficulty using contexts to limit fear responses.
* Associated with impaired Hcc and vmPFC activation and exaggerated dPFC activation.
* Absence of LTP in the PFC impairs the contextual regulation of the fear response.
* with reduced PFC activity when exposed to emotional cues
91
Some studies of PSTD report reduced Hcc activity, but not all agree, what is going on with this?
found out that hippocampus might actally be a prediposing factor instead of a symptom of PTSD
92
Individuals suffering from PTSD exhibit difficulty doing what? Why?
* using contexts to limit fear responses
* Associated with impaired Hcc and vmPFC activation and exaggerated dPFC activation
93
Associated with impaired Hcc and vmPFC activation and exaggerated dPFC activation can lead to what?
Intrusive thoughts, memories and perceptions may represent a loss of contextual control of extinction
94
The Prefrontal Cortex is Critical for _
Discrimination
95
Both specific cues and contexts can increase _ activity and produce _ and/or _.
Both specific cues and contexts can increase **BLA** activity and produce **fear** and/or **anxiety**.
96
Discriminating safe from dangerous cues and contexts requires the synchronous activity of what?
of the mPFC and BLA
* Safety is signaled when activity in the mPFC precedes BLA firing.
97
What happens when there is desynchrony between mPFC and BLA
generalization of fear and anxiety occurs.
98
Neuromodulators enhance ongoing _, strengthening contextual and cue-elicited fear. How?
LTP
* Ca++ influx triggers 2nd messenger systems and reconsolidation of fear memories
99
The absence of LTP in the PFC impairs what
contextual regulation of the fear response
* cannot extinguish fear
100
What is required for extinction? why is this important?
BDNF-> decrease levels in PTSD
101
What is wrong with the brain in panic disorder, specific phobias, and social anxiety disorders?
**Panic Disorder**
* Associated with increased arousal in AMY, vmPFC, dlPFC, and brain stem; low GABAa receptor binding-> cannot inhibit nervous system activity
**Social Anxiety Disorder**
* Exaggerated amygdala activation only consistent finding
**Specific Phobias**
* AMY and dlPFC hyperresponsive to specific cues
102
Explain amygdala and addictive behavior
Main points:
* cocaine increases amygdala-mediated craving
* NMDA agonist into amygdala increases drug cravings
* Suggests that drug craving, a mechanism for recidivistic behavior, is mediated by withdrawal-related changes to the amygdala
103
What are the 4 psychotherapies for PTSD?
104
What is 1st line for anxiety disorders?
Cognitive Behavioral Therapy (CBT) is 1st line for anxiety disorders
105
What are some medication used for PTSD and anxiety disorders?
1. SSRI’s and SNRI’s
2. Benzodiazepines
3. Pregablin
4. MDMA-assisted psychotherapy
106
1. Scientists at the Morsani College of Medicine are studying the effects of lesions to various portions of the brain. One lesion in particular led to extreme fits of rage where lab mice began attacking scientists. Given the temperance of the mice, where was the lesion likely administered?
A. Amygdala
B. Cingulate Gyrus
C. Neocortex
D. Septum
D. Septum
107
2. Fear conditioning studies often train mice to associate noxious stimuli (i.e. shock) with specific contexts and/or cues. Which of the following terms best describes a cue (i.e. tone) after training?
A. Unconditioned Stimulus
B. Neutral Stimulus
C. Conditioned Stimulus
D. Unconditioned Response
C. Conditioned Stimulus
108
3. All of the following nuclei are correctly paired with their respective function EXCEPT:
A. Lateral Amygdala (LA); Consolidation of fear
B. Accessory-Basal Amygdala (AB); Extinction of fear
C. Lateral Central Nucleus (CEl); Expression of fear
D. Baso-Lateral Amygdala (BLA); Experience of fear
C. Lateral Central Nucleus (CEl); Expression of fear
109
4. A 27-year-old army veteran has enrolled in a clinical trial studying the effects of traumatic experiences on brain function. If the veteran was suffering from post-traumatic stress disorder (PTSD) at the time of the study, what would scientists likely observe?
A. Exaggerated dPFC activation
B. Increased long term potentiation in the PFC
C. Hyperactivity of the Hippocampus and vmPFC
D. Elevated levels of BDNF in the IL-PFC
A. Exaggerated dPFC activation
110
5. Which of the following therapies would be most beneficial for someone suffering from an anxiety disorder?
A. Prolonged Exposure Therapy
B. Cognitive Behavioral Therapy
C. Stress Inoculation Training
D. Cognitive Processing Therapy
B. Cognitive Behavioral Therapy
