Limbic & Autonomic Systems

1. Limbic & Autonomic Systems Brent A. Vogt, Ph.D.

3. Limbic Systems by Iversen, Kupfermann, Kandel Page 984“Feelings are cognitive translations of ambiguous peripheral signals.” What is a feeling?

4. Limbic Systems by Iversen, Kupfermann, Kandel Page 987“The limbic system consists of the limbic lobe and deep lying structures.” In light of Fig. 50-4, is the hippocampus part of the limbic system?

5. Limbic Systems by Iversen, Kupfermann, Kandel Page 994“The hippocampus has only anindirect role in emotion.” Is the hippocampus part of the limbic system and is it involved in emotion?

6. Limbic Systems by Iversen, Kupfermann, Kandel Page 988“The amygdala is the part of the limbic system most specifically involved with emotional experience.” What does “most specifically” mean? Are there less specific involvements? What is emotional experience?

7. Limbic Systems by Iversen, Kupfermann, Kandel What is the limbic system?What are its functions? What is emotional information?Fig 50-8 only shows emotion as output from Central nuc of AmygdalaIs that the only limbic/emotion nucleus?

8. Limbic Systems by Iversen, Kupfermann, Kandel The major problems in limbic system research are 1. Failure to integrate human imaging2. No consistent theoretical context.

10. Components of Limbic Systems 1. Periaqueductal gray; PAG 2. Hypothalamus/HPA Axis3. Amygdala 4. ACC/insula5. MCC6. DRN/LC7. Autonomic Nervous System

11. Limbic Structures & Key Functions 1.PAG Coordinated behaviors; Autonomic/Skeletal 2.Hypothalamus/HPA Axis Autonomic/hormonal control 3.Amygdala Simple significance codes/valences; mostly fear 4.Anterior cingulate (ACC) & Insula Store Emotional/Valenced information Recode amygdala 5.Midcingulate cortex (MCC) Predict outcomes & Resolve ambiguity Select outputs; mental or movement decisions Devise new behaviors for new problems 6a.Dorsal Raphe Nucleus (DRN) Regulate mood 6b.Locus coeruleus (LC) Coordinate responses to events & Enhance valenced memories 7.Autonomic Nerv Sys (ANS) Supports skeletomotor output & Enhances CNS memory of valenced objects/events

12. Emotion Involves Valencing Objects/Events

13. Emotional Motor Systemsfor Expressing Emotion Primary & Secondary Emotions Structures that regulate ANS/Fight-or-FlightCentral AmygdalaSubgenual ACCPVN, HypothalamusVentrolateral PAGLC

14. PAG: Coordinates Emotional BehaviorsGenerates Primary Emotions 1. Location 2. Two Functional Modes 3. Norepinephrine (NE)/LC Selects F-or-F Mode

15. Electrical Stimulation of Hypothalamus (VMH/Lat) or PAG Evokes Integrated Behaviors 1. Location 2. Stimulated Defense or Eating 3. Stroke/tumors to Hypothal PAG can produce Sham Rage Fully integrated rage without external control e.g., a fly on nose & excess rage

16. PAG Regulates ANS via Projections to NTS,DMX, IML

17. Hypothalamus ControlsHormone Response: HPAA 1. Pituitary Location 2. Limbiccortex drives PVN to secrete CRH into portal veins. CRH evokes release of ACTH from the pituitary which evokes release of cortisol from adrenal cortex. Cortisol binds glucocorticoid rec. to ↑ glucose levels & metabolism, amino acid metabolism, fat breakdown, release of neutrophils & ↑ memory 3. NE/LC Drives PVNHPA Axis

18. Amygdala & Fear 1. Location 2. Central nucleus regulates cardiovascular output Lateral nuclei receive sensory cortex input for coding significance/valence Kluver-Bucy Syndrome follows amygdala damage a. Docility b. Absence of emotional expression c. Paucity of social interactions d. Hyperorality/obesity e. Visual agnosia f. Impaired short-term memory Amygdala stores simple significance codes mainly for fear (hissing snake, growl of dog, raised knife, flushed face)

19. Amygdala Involved inFear Perception, ANS Response & Memory 3. 2. 1. 5. 4. Memory of object/event 6. NE/LC Enhances Negative Memories

20. Case of Bilateral Amygdala Damage Lipoid proteinosis with rage & loss of recent memory & complete loss of the amygdala (white arrows) SM-046 could not judge intensity of facial fear. She understood non-threatening faces and made judgments with verbal information. She could draw fearful faces from memory & prompting but claimed they were not accurate. Amygdala codes for objects and events of non-conscious or conscious fear. Behavior after amygdala damage reflect miscoding of fearful events, lead to excessive risk taking, odd relations & financial decisions. Symptoms of amygdala damage

21. Affect & Motivation in Cingulate Gyrus (Flat map) 1. Location 3. MCC: Resolves conflictRegulates skeletomotor output MCC ACC 2. ACCStores Valenced MemoriesRegulates ANS

22. ACC Stores Memories of Sad Events Positron Emission Tomography (PET) study of healthy women remembering sad events Summary of functional imaging studies of simple emotionsFear, Sadness & Happiness are segregated

23. ACC Mediates ANS Activity With the Amygdala ACC projects to autonomic brainstem: Nuc of Solitary Tract & DMX Stimulation at V evoked pure fearat H evoked “desire to leave room”

24. Amygdala Projects to ACC Axon terminal labeling (dots)Monkey[3H] Amino acid injection(hatched)

25. Amygdala & Cingulate Cortex Interact During Fear Red/yellow + correlationsBlue – correlations This connection disrupted indepression &posttraumatic stress disorder

26. Electrical Stimulation of MCC Evokes Complex Skeletomotor Responses adapted to Context lip puckering,finger kneading,bilateral limb movements(not single muscle/muscle groups like motor cortex) Kissing, scratching, pushingActivities that are valenced & context dependent

27. I I II II IIIab IIIab IIIc IIIc Va Va Vb Vb VI VI CinguloSpinal/Layer Vb Projection Neurons MCC Directly Regulates Skeletomotor Behavioral & Emotion Relevant Activity

28. Facial Region of the Cingulate Motor Area:Expressing & Interpreting Emotional States All emotions can impactthe facial region in ACC The Facial Region Projects to the Facial Motor Nuc;Muscles of facial expression

29. Interpreting Internal Emotional States:Empathy Facial ambiguity is not resolved in amygdala What is this bride’s face saying about her emotional state ?ACC uses context information

30. Internal State and Expression ofComplex Emotions Requires ACC Context resolves complex and ambiguous emotional states Can you now understand what this woman is saying with her face?

31. LC Pivotal to F-or-F Systems LC regulates HPA axis via PVN & ANS by projections to NTS/DMX

32. Locus CoeruleusMediates F-or-F & Emotional Memories LC & PVN are reciprocally connected Activation of the PVN by allostatatic-stress signals from prefrontal/cingulate cortices drive LC LC releases NE in thalamus, amygdala, and cortex to enhance memories associated with ANS output; i.e., beating heart and heavy breathing Storage of memories of valence codes in amygdala and significance/context in ACC depends on NE/LC

33. LC/NE Integrates Limbic Motor Systems 1. NTS/PVT mediate heart rate responses in sACC/Central Amyg 2. PAG:NE selects F-F 3. PVN drives HPA Axis;NE, ACTH, Cortisol 4. Enhances Amygdala processing & memory

34. Overview of Limbic Motor Systems

35. Dorsal Raphe Nuclei (DRN) 1. Located in Midbrain 2. Serotonergic (5HT) neurons 3. Project to forebrain (Amygdala & ACC) 4. Determines tonic activity

36. The DRN Regulate Mood

37. Limbic Diseases Are Associated withDisordered Behaviors Depression Reduced reactivity to the environment & Lack of emotional responsivityAnxiety and sometimes panic Traits are genetic predispositionsassociated withbehavioral & neuronal phenotypes

38. Prodromal Depression:Predisposition before Symptoms 1. Up to 70% cases inherited2. Short variant polymorphism in 5HT Transporter;Chromosome 17q12Reduces transcription efficacy of the 5HTT3. Associated with trait anxiety and risk of depression

39. “Normals” with Short 5HTT alleleShrunken sACC & Amygdala 1. Reduced Functional Interaction of sACC & Amygdala 2. Amygdala uncontrolled by ACC/MCC associated with enhanced fear – anxiety

40. Major Depression State withReduced ACC Size & Sad Activation Positron Emission Tomography study of glucose metabolism

41. Highest 5HTT Density in ACC Citalopram binds to 5HTTHeaviest binding in ACC accounts for clinical efficacy ofselective serotonin reuptake inhibitors (SSRI); paroxetine

42. 5HT Therapeutic Targets for Depression

43. Pharmacotherapy for Depression Enhance 5HT Function in ACC & Amygdala