1. The Limbic System Dr. Kenira J. Thompson Ponce School of Medicine Dept. of Physiology 840-2575 Ext. 2166 Email: kthompson@psm.edu

2. Lecture Goals Review functional anatomy of the limbic system Describe behavior and cognitive disturbances associated with limbic system pathology.

3. “Is emotion a magic product, or is it a physiological process which depends on an anatomic process?” (Papez, 1937).

6. Broca’s Limbic Lobe, 1878 (“Le Grand Lobe Limbique”) C’est magnifique!

7. Limbic Functions (HOME) Homeostatic functions (autonomic and endocrine control) Olfaction Memory Emotions and Drives

8. What is the limbic system? Set of interconnected cortical and subcortical structures that form a border (or limbus) around the brain stem.

9. Main Components Limbic cortex Parahippocampal gyrus, cingulate gyrus, Medial Orbitofrontal cortex Hippocampal formation Dentate gyrus, hippocampus, subiculum Amygdala Olfactory cortex Diencephalon Hypothalamus, thalamus (anterior nucleus, mediodorsal nucleus) Basal Ganglia Ventral striatum (Nucleus Accumbens, Caudate, Putamen) Basal forebrain Septal nuclei Brainstem Also includes the tracts that link these structures: fornix, mammillothalamic, stria terminalis, etc.

14. Papez Circuit James Papez (1937) Was the first to identify that emotion is not a function of any specific brain center but a circuit involving 4 basic structures.

15. Revised Papez Circuit Paul McLean (1970)- Revised Papez’s theory and called the circuit the limbic system. Added more structures to the system: Prefrontal cortex Parahippocampal gyrus Important subcortical structures (amygdala, thalamic nuclei, septal area, etc.).

16. Neocortex Emotional experience Cingulate cortex Hippocampus Anterior nuclei of Thalamus fornix Hypothalamus Emotional expression

17. Three limbic circuits Amygdala-Hippocampus Affects behaviors related to self-preservation Cingulate gyrus- septum Relates to pleasure, especially sexual enjoyment (stimulation of this region in rats results in penile erection, self-grooming) Hypothalamus-anterior thalamus Important for cooperative social behavior

18. 1 Cingulate Gyrus CAUDATE CC

19. Anterior nucleus thalamus Fornix CINGULATE T Mamillary bodies Parahippocampal gyrus

20. Cingulate Gyrus and Depression Depressed Patient After Fluoxetine

21. Hypothalamus

23. Damage to hypothalamic nuclei results in: Abnormalities in motivated behaviors such as feeding, drinking, sexual behavior, fighting, temp. regulation. Also regulates secretion of hormones via the pituitary gland (secretions control other endocrine organs, such as the thyroid, adrenal glands, ovaries, testes).

24. Brain transections and sham rage

25. Rage reaction in cats with hypothalamic stimulation

26. Korsakoff’s Syndrome Severe anterograde amnesia Results from thyamine deficiency (Vit. B1) Usually caused by alcoholism Severe degeneration of mammillary bodies. Patients tend to confabulate to cover up memory deficit

29. 3 STRIA TERMINALIS Fx H TEMPORAL LOBE P Temporal Lobe Amygdala

31. Amygdala Nuclei

32. Amygdala Projections

34. Amygdala Lesions Result in: Reduced ability to identify motivational and emotional significance of events Electrical stimulation of amygdala can lead to emotional attacks (rage) Rabies virus (especially attacks the temporal lobe) leads to violent behavior

37. Kluver-Bucy Syndrome Results from bilateral removal of the amygdala and inferior temporal cortex. Includes: Tameness, loss of fear Indiscriminate dietary behavior Greatly increased autoerotic sexual activity Tendency to attend to every visual stimulus Tendency to examine all objects by mouth Visual agnosia (cannot recognize objects visually) Inability to recognize facial expression

38. Human brain activity in response to emotional stimuli

39. Amygdala activity associated with enhanced emotional memory

40. Central nucleus (Autonomic Response) (Behavioral Reaction) (Emotional Experience) Hypothalamus Auditory cortex PAG BLA Cerebral cortex Neural circuit for learned fear Tone

41. A neural circuit for aggression

42. Emotion and Memory

43. Hippocampal formation…why is it important? Making new memories Involved in severe mental illness Reduced volume in schizophrenia, PTSD, depression Directly affected by estrogen (Wooley, NWU) Neurogenesis

44. 4 Mammilothalamic tract A Mamm PHG Temporal Lobe Hippocampus

47. Hippocampus (cortical connections)

49. Neurogenesis

50. Hippocampus and Alzheimer’s Disease

51. Ischemia

52. Hippocampus and Depression

53. Hippocampus and Estrogen

54. Reward System Projections This will make me famous! Self-stimulation Reward pathways DOPAMINE

55. 2 C P Nucleus Accumbens

56. Dopamine receptors (D3) in Nuc. Accumbens Cocaine Addict