Prof. Anagnostaras, Lecture 7: Fear

Transcription

1 Historical views that thought and emotion were processed separately in the brain Prof. Anagnostaras, Lecture 7: So far, fear is the best understood What is fear? Dictionary: A feeling of agitation and anxiety caused by the presence or imminence of danger My definition: an adaptive emotional state which motivates and organizes defensive responses necessary for survival. is inferred by the presence of defensive responses. It is indexed by the level of those responses. Issues in What is innate or unlearned fear? - Inherited (instinctive) fear e.g., loud noise, painful stimuli - Stimuli that produce innate fear are called unconditional stimuli (USs) What is conditioned fear? Acquired fear enhances the adaptive value of innate fear. Most fear is acquired. Conditional stimuli (CSs) acquire fear by being paired with USs Species that exhibit learned fear have a distinct adaptive advantage All animals rapidly acquire learned fear Two kinds of learning ( & Avoidance) CONDITIONED FEAR Classical (Pavlovian) fear conditioning CS is paired with US (red stove-heat) generalizes to CS Environment controls subject AVOIDANCE Instrumental (Operant) conditioning Response is paired with US (touch-pain) Avoid response because of expected US Subject controls environment Always occur together, but dissociable 1

2 memories are robust and long-lasting memories are robust and long-lasting Pavlovian: Sight of plane elicits fear. Instrumental: Avoid flying. Conditioned fear is very rapid (1 trial) and very long-lasting (forever) Pairing Pairing Conditional Stimulus, CS Unconditional Stimulus, US Unconditional Response, UR () Memory Process: Association Pairing Pairing Memory Process: Association Memory Process: Association Conditioned Response, CR: Conditioned Response, CR: State Responses Freezing Potentiated Startle Blood Pressure Flight... 2

3 Pavlovian fear conditioning protocol Pavlovian fear conditioning protocol CONTEXT TEST Freezing response measured CR = Freezing Training Context Testing Context US Bright White Lighting Grumbling Noise Ammonia Odor Flat Grids Bright White Lighting Grumbling Noise Ammonia Odor Flat Grids Pavlovian fear conditioning protocol CONTEXT TEST TONE TEST Alternate Context CR = Freezing Baseline Period Dark Red Lighting Triangular Insert White Noise Vinegar Odor Staggered Grids potentiated startle Unconditioned Circuit: Central Nucleus of the Amygdala and its Outputs McNish, Gewirtz, & Davis, Beh Neurosci, 2000 AMYGDALA = "ALMOND" 3

4 Lee Walker & Davis (1997) Within-subjects design REMOTE 480 d later RECENT Sham or Basolateral Amygdala Lesion RECENT TONE REMOTE TONE REMOTE CONTEXT RECENT CONTEXT Amygdala has temporally-stable role in fear memory. Forever? The basolateral amygdala is involved in lifelong retention of fear memories Remote and Recent training separated by sixteen months Dorsal hippocampus lesions produce a highly selective deficit in recent contextual fear memory Content could be: Context-shock association Just memory of the context 100 Context Summary 100 Summary Doesn't matter how old the fear memory is or what kind of fear memory. Amygdala lesions DO NOT affect many other forms of learning, however (e.g. maze learning or word lists) Remote Recent (first six min) Remote Recent (six min) Sham DH Unconditioned Circuit: Central Nucleus of the Amygdala and its Outputs Circuit for fear-potentiated startle identified by M. Davis & colleagues 4

5 Basic model that has emerged for Pavlovian fear conditioning Unconditioned Circuit: Central Nucleus of the Amygdala and its Outputs thalamus Innate fear Learned fear Central nucleus outputs coordinate all of the defensive responses (learned and innate). Central nucleus = output of fear/unlearned fear Basolateral/lateral nucleus = learned fear Circuit for conditioned freezing identified by Fanselow, LeDoux & colleagues Basic model that has emerged for Pavlovian fear conditioning context Footshock Periaqueductal grey (freezing) Most research focused on what the synaptic changes are at the point of convergence in the lateral/ basolateral amygdala Storage and "Stamping in" roles of the Amygdala Modulatory model proposed by McGaugh et al. CS-US associations (Pavlovian fear) in the basolateral amygdala. can also "stamp" in emotional memories elsewhere (video next class). Amygdala sends upstream connections to signal danger and reinforce "cognitive" memories elsewhere (cortex). amygdala can store memory or stamp in memory elsewhere 5

6 AVOIDANCE fear conditioning Passive avoidance (Jim McGaugh) - shock on one side of the box - avoids that side - Neurobiology not clearly understood, only partially overlaps with conditioned fear - Probably mediated by "cognitive" representations in the cortex Pavlovian fear, Phobias, and Anxiety 1. Conditioning model of phobias 2. Problem is not everyone develops phobia, and in anxiety disorders there is the problem of overgeneralized threat 3. Likely reflects genetic predisposition -more likely to interpet threat -- but most studies done in normal lab rats 4. Combine with traumatic event to produce characteristic disorder Genetically modified mice (xx) Elevated plus maze - unlearned fear test several hyper-anxious mutant mice Most candidates are changes in GABA or serotonin receptors, or in stress hormone receptors (CRH) Drugs used to treat abnormal fear: Anxiolytics (benzodiazepines) enhance GABA-A Serotonin-specific reuptake inhibitor (SSRIs) (Paxil) enhance serotonin Open Field Crhr2 knockout total deletion of gene for corticotropin releasing factor receptor type 2 Spiess et al. Nat Gen 6

7 GABA-A receptor subunits Can be made from 18 different genes GABA-A γ2 heterozygous deletion produces Hyper-anxiety (innate fear) Crestani et al. Nat Neurosci Hypersensitivity to diazepam Hypersensitivity to learned fear Altered sensitivity to fear conditioning Complex genetically-produced syndromes more reminiscent of anxiety disorders Small alternations in various anxiety-related genes may lead to anxiety disorders, I.e., increased threat appraisal -Traumatic events bring out various disorders Especially irrational phobias -Some events sufficient to produce phobia or anxiety disorder in anyone? 7