Amygdala, Fear, Emotion
Describe extinction acquisition.
-Animal placed in a new environment and exposed to the cue (without shocks) -Initially they have a strong response; it diminishes as time goes on ONLY OCCURS FOR THAT SPECIFIC CONTEXT
What is the mechanism by which the hippocampus modulates the fear response across different contexts?
-hippocampal projections to BLA synapse on inhibitory interneurons —> inhibits neurons which projects to neurons of the CEA (modulates the fear response across different contexts) so if you damage the hippocampus, you lose the ability to regulate repsonse across different contexts
What are the 2 pathways mediated by hippocampal (Hcc) projections?
1)Hcc —> BLA and HCC —> PL —> BLA - involved in context dependent expression of fear 2) HCC —> IL —> CEA -involved in suppressing fear responses following extinction
What is the effect of prolonged fear?
1. increased activation/sensitization of BNST (via CRF) 2. inhibition of CEm
Stimulation of CRF receptors on the BNST results in ________
1. sensitized startle response 2. facilitates responding to long duration cues 3. facilitates contextual conditioning (ANXIETY/VIGILANCE!!)
What percent of US adults are affected by anxiety disorder each year?
18% (PTSD, panic disorder, social anxiety disorder, phobias) all are regulated by dysregulated fear/anxiety response
What changes take place in the LA during fear conditioning?
After conditioning, there is a sharp response from the LA that occurs much sooner than before
Panic disorder is associated with increase arousal in ____________.
Amygdala vmPFC dlPFC brainstem low GABAa receptor binding
What are the structures involved in fear?
Amygdala - Basolateral amygdala (LA, B, AB) and Central nucleus (CEl, CEm) Median eminence of the hypothalamus (divides the Amygdala and hypothalamus
What is controling LA response before and after conditioning?
Before - cortical control; slower After - strengthens THALAMIC control ; faster response you are losing the conscious component; its just a reaction; no inculsion of thought/cognition
What are the 3 neural circuits that regulate emotionally driven behavioral tendencies?
Behavioral approach system - response towards something that will satisfy a desire Behavioral avoidance system - fight or flight response Behavioral inhibition system - keeps you from wasting energy e.g. when you are stuck in traffic, emotional arousal makes you curse...doesn't serve any functional purpose -your'e just wasting energy having an emotional response that doesn't acheive anything
When in danger, activation of the PVS leads to fight or flight. If that is impossible, what happens?
Behavioral inhibition system is activated
What is the evidence behind the conclusion that the amygdala is critically involved in the experience of fear?
Bilateral amygdalectomy --> reduced fear/aggression anger, sadness, and disgust may also be affected electrimal stimulation of amygdala --> increased vigilance/attention fearful faces produce greater amygdala activity than happy/neutral faces
Blockade of _________ interferes with cue elicited fear conditioning
Blockade of NMDA receptors in the LA and VG Ca-channels in the LA
The basal and accessory basal amygdala receive projections from ___________
CA1 and the subiculum of the HIPPOCAMPAL FORMATION
So, the CEm mediates __________ responses to fearful stimuli, while the BNST mediates responding to _________
CEm - response to conditioned stimuli BNST - response to undonditioned stimuli
Extinction is ________ specific.
CONTEXT A fear inducing CS will produce fear in any context However, repeated CS exposure in a new context without a US, will lead to extinction in that context
What hormone acts on the BNST
CRF from the hypothalamus (it is very rich in CRF receptors)
What is the mechanism by which neuromodulators enhance LTP?
Ca influx triggers 2nd messenger systems and consolidation of fear memories
What does the Papez circuit connect?
Connects the hypothalamus to the limbic lobe (via the anterior nucleus of thalamus and the hippocampus)
Describe contextual fear pairing vs cue elicited fear pairing
Contextual fear pairing - placed in the same environment where learning took place; no tone presentation Cue elicited - Animal place in new environment; exposed to same tone; separating the context from the cue
Which structures are part of Broca's Limbic Lobe?
Cortex surrounding the corpus callosum (neocortex) Cingulate gyrus Medial surface of the temporal lob Hippocampus
How does PTSD develop?
Each time the fear is re-expressed, it is an opportunity for reconsolidation leads to generalization and sensitization (associating unrelated cues to the original event) this strengthens the overall memory and the network which can activate that memory
Intrusive thoughts, memories and perceptions may represent a loss of contextual control of ________.
Extinction
What is the difference between fear and anxiety?
Fear is an emotion; short lived; serves to promote action Anxiety is a mood state; sustained arousal/vigilance in response to vague potential threats Anxiety does not initiate an action; it biases your cognition. Fear promotes action (there is likely overlap between the 2 circuits)
After extinction acquisition, if an animal is placed in a novel environment, what happens?
Fear response returns (the context is regulating the fear response)
Which areas of the brain are prone to LTP and sensitization early on after a stressful experience? Which area is not?
Hippocampus and amygdala (the prefrontal cortex is not!) (The temporal window for LTP is short, protecting the Hcc and AMY from excitotoxic effects)
If the hippocampus has been lesioned, how does the animal respond after extinction?
In normal animals, after extinction, they are no longer fearful in that one specific context With a hippocampal lesion, they are no longer responsive in ANY context after extinction
The function of the hippocampus is context regulation? How does this come into play in the septo-hippocampal circuit?
In what context do we need to be fearful? based on past experiences, if we do need to be fearful, activation of the BLA is anxiogenic, and will result in a state of heightened attention/arousal (anxiety)
What is the role of the medial central nucleus?
It is the primary output for behavioral responding
Which region specifically is critical for the cue elicited fear response?
LA (lesions of B and AB have no effect on fear conditioning
These neuromodulators released during a strong emotional experience have been shown to enhance ________
LTP (strengthening contextual and cue elicited fear) (mechanism for PTSD establishment during reconsolidation)
What is the mechanism for development of cravings after cessation of cocaine abuse?
LTP in the amygdala (via NMDA receptors) probably the connection between the BLA and BNST, which can increase anxiety this motivates behavior --> alleviated by taking drug again
What are the 3 nuclei of the basolateral amygala
Lateral (LA) Basal (B) Accessory-basal (AB)
Why is the thalamus able to regulate the lateral amygdala response more effectively after cue-elicited fear conditioning? In other words, what is the mechanism that allows for cue elicited fear conditioning?
Long term potentiation (learning!) Shock pairings —> increased neuronal firing in the lateral amygdala —> Ca influx —> second messenger cascapde —> increased expression of AMPA receptors —> increases sensitivity of post-synaptic neuron to subsequent stimulation
In the behavioral approach system, when a gratifying action is possible, the __________ is activated
MFB (medial forebrain bundle) (part of the reward system)
How do we know that the lateral central nucleus (CEl) is involved in learning
NMDA antagonism --> no acquisition of fear conditioning (no learning) block protein synthesis (no consolidation/no learning)
What is the function of each area of the Papez circuit?
Neocortex - applying cognition/thought to that experience (emotional coloring) Cinculate cortex --> emotional experience Hypothalamus -- emotional expression (action) Hippocampus and anterior nucleus of the thalamus --> interconnection
A strong emotional experience activates _______ release
Neurotransmitter: (Glu, Ne, ACh, DA) Stress hormone (CRF, ACTH, glucocorticoid)
What is the 4th most common psychiatric diagnosis?
PTSD
Most of what is known about the neurobiology of fear comes from ___________ experimentation
Pavlovian conditioning
Individuals with PTSD have reduced ________ activity when exposed to emotional cues. What is the effect
Prefrontal cortex (ventral medial PFC) Normally, the PFC is involved in contextual regulation of fear So if its activity is reduced, the person has difficulty using context to limit fear responses --> leads to reconsolidation and generalization
What are the 3 symptoms associated with PTSD?
Re-experiencing trauma (intrusive thoughts, nightmares, flashbacks) avoidance of social situations; emotional detachment exaggerated startle; hypervigilance in response to trauma related stimuli
Describe the path of the septo-hippocampal circuit
Selective activation of the BLA activates the ventral hippocampus (anxiogenic) Activation of the vHcc inhibits the septal area, which disinhibits the amygdala to produce a state of anxiety
What is the extended amygdala?
The amygdala plus the BNST (bed nucleus of the stria terminalis) the are located far apart, but direct projections exist all one very diffuse structure
Which structure is involved in extinction?
The hippocampus (also involved in CONTEXT regulation)
Describe the fear acquisition phase of the fear response
Training period usually about 10 pairing to make a strong conditioned response Results in intense fear retrieval for both contextual and cue fear tests
What is the unconditioned stimulus and unconditioned response?
US = shock UR = freezing (eventually they become the CS and CR)
All anxiety disorder have the consistent response of ________
a hyperresponsive amygdala
What is learned helplessness? What causes it? What is the effect?
a perceived lack of control in environment (if you cannot engage in a response to alleviate a stressful experience) causes prolonged levels of anxiety and stress hormones shuts down the system - intead of responding to stressors with action, you respond with passiveness (depression)
Specific phobias are associated with
amygdala and dlPFC hyper responsive to specific cues
Which neural circuit is fear a part of?
behavioral avoidance system
What are the 2 types of fear that are tested for with fear conditioning?
cue elicited fear Contextual fear
What type of behaviors are motivated by fear? How does fear affect the nervous system?
defensive behaviors, arousing the ANS for fight or flight
People with PTSD also show increased _______ activity
dorsal PFC
Lesions of the BLA impair _________
emotional responding to shocks both cued and contextual fear conditioning
Emotions give behavior ________
energy and direction (they do not lead to programmed motor sequences; that is where learning comes in to play)
Social anxiety disorder is associated with __________
exaggerated amygdala activation
What is the result of a septal lesion
extremes of emotions - explosive violence;
Context related events are anticipated by the _________.
hippocampus "to be afraid, or not to be afraid..."
PTSD is associated with dysfunction in which area?
hippocampus Remember: hippocampus involved in contextual regulation of the fear response -If damaged, contextual information is no longer regulating the cue-elicited fear response
When do emotions become maladaptive?
they are adaptive when they prioritize behaviors to optimize adjustment to ongoing demands they are maladaptive When they prioritize behaviors that interfere with effective adaptations e.g. -- Adaptive :Fear of being bitten by experimental animals motivates the student to seek out training and to practice extensively Maladaptive: Fear of being bitten by experimental animals motivates the student to avoid laboratory obligations that involve animal handling
What are the two pathways by which the hippocampus is connected to the BLA?
via the vmPFC (pre limbic area) and direct pathway: Hcc --> BLA
When do we experience fear?
when there is a perceived vulnerability to being overwhelmed by a threat or danger
When is the BIS (behavioral inhibition system activated?
when we observe our actions will be ineffective
Emotions are a biopsychosocial phenomenon that CAN promote adaptation during important life events. What is a biopsychosocial phenomenon?
short lived - rapid onset/offset affects biology/physiology can influence social interactions provide a motivational state to promote action produce a subjective state of personal significance communicates to others how we interpret our present situation
James Papez is credited with proposing that _________________.
specific brain circuits are devoted to emotional experience and expression
What is the function of the BIS?
suppresses the link between emotion/motivation and behavioral output prevents wasted effort this is a protective system, designed to protect you from things like ulcer, HTN, cancer, etc (which are the result of chronic elevated stress hormones) can be maladaptive --> depression
Removal of _______ results in Kluver bucy syndrome. What is the effect?
temporal lobectomy decrease fear and aggression decreased vocalization and facial expression
Inhibition of the CEm means that we cannot produce a response, so what happens next?
that stimulates the BNST --> anxiety
The CEA is the interface between ____________
the BLA and the motor systems involved in expression of the fear response
When danger is sensed, what is activated?
the PVS (periventricular system) Amygdala, septo-hippocampal circuit
Kluver budy syndrome is probably related to destruction of ________.
the amygdala
The BLA receives input from _________. This means it is the ideal location for _______.
the auditory/visual cortex and auditory/visual portions of the thalamus somatosensory input (pain) its receiving input related to experience of the shock (US) and related to cues (auditory/visual) -so its an ideal place for conditioning to take place
What are tone responsive cells?
the population of cells responsive to the presence of the tone in the auditory cortex and LA the both show increases in firing after presentation of a tone
The septal "sham" rage is the result of disinhibition of the ________
hypothalamus (controls emotional expression)
What happens if you lesion the CEm?
if you lesion the CEm, you have no fear (at least no measurable expression of fear) there may still be learning, but it couldn't be measured if you only lesion specific projection areas, there would only be selective loss of responses
What is the main function of the CEl?
it regulates the response initiated by the LA (disinhibits/inhibits) the CEm Remember: the CEm is critical for expression of the fear response (the measurable part)
What do lesions of the hippocampal formation cause?
no effect on emotional responding to shock (because it doesn't project to LA) impairs contextual, but not cue elicitedd fear (because cue elicited fear is mediated by LA) so hippo is involved in contextual regulation of the fear response
The amygdala produces more _________ during craving.
pERK (phosphorylated extracellular regulated kinase) (infusing NMDA --> activates ERK --> speeds up craving)
What is the function of the median eminence of the hypothalamus?
releases CRH