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  • Originally thought to be involved primarily in olfaction (“rhinencephelon”) - BROCA - cingulate and PHG
    No known to also be involved in emotion, memory
    General structures: subcallosal gyrus - isthmus - PHG . Medial is HC, and ant. Medial is amygdala; deep to subcollasal is the septal nuclei
    More specifically limbic system gives you honest info about your emotional state. Neocortex provides excuses for why your are feeling that emotion. Hypothalamus - visceral sensations to that emotion.
    For example: so say all of a sudden your heart rate goes up, you hands get sweaty.. (product of your hypo) and you say to yourself its because you are nervous say for an inyour neocortex
    Papez believed the limbic system was the connection between hypo and neocortex; producing a general stream of emotion; papez circuit is HC via fornix --> mammillary bodies via mammilothalamic tract --> Ant. Nucleus of thal --> cingulate gyrus --> PHG --HC.
    Rabbit --> cat --> monkey --> human ; limbic system gets smaller proportinally to cortex.
    Various deficits resulting from damage to these different areas.
    1. Amydala and surrounding periform cortex bilaterally - Kluver Bucy Syndrome - hyperorality (damage to area 20), no anterograde memory (short term memory - HC), calm (no longer aggressive- amgydala), hypersexuality (
  • Exercise-induced increases in dentate gyrus CBV correlate with neurogenesis. (a) (Left) Exercising mice were found to have more BrdU labeling compared with the no-exercise group. (Right) As shown by confocal microscopy, the majority of the new cells were colabeled with NeuN (red, BrdU labeling; green, NeuN; yellow, BrdU/NeuN double labeling). (b) (Left) A significant linear relationship was found between changes in dentate gyrus CBV and BrdU labeling. (Right) A quadratic relationship better fits the data. The vertical stippled line in each plot splits the x axis into CBV changes that decreased (left of line) versus those that increased (right of line) with exercise.
  • A taxonomy of long-term memory systems together with specific brain structures involved in each system (adapted from ref. 66).
  • Right vs. left (combined allo vs. ego)
  • Various deficits resulting from damage to these different areas.
    Amydala and surrounding periform cortex bilaterally - Kluver Bucy Syndrome - hyperorality (damage to area 20), no anterograde memory (short term memory - HC), calm (no longer aggressive- amgydala), hypersexuality (periform ctx),
  • You can get endocrine release patterns, autonomic discharges, can produce changes in the body set or configuration, and the awareness of your own and others facial posturing. The discharge from the amygdala down the brain stem goes to the vagal complex, solitary. It is capable of continuously modulating emotions.
  • Randomized, counterbalanced order
  • Transcript

    • 1. Hippocampus & Medial Temporal Lobe Functional Neuroanatomy November 12, 2009 Nanthia Suthana, Ph.D. Cognitive Neurophysiology Laboratory Department of Neurosurgery
    • 2. Felleman & Van Essen (1991)
    • 3. PHG Mamillary Bodies HC LIMBIC SYSTEM (cingulate gyrus, PHG, hypothalamus, septal area, nucleus acumbens, orbitofrontal ctx, amygdala) Subcallosal Gyrus Fornix Cingulate Gyrus Ant. Nucleus of Thal Olfactory bulb Septal Nuclei Amygdala Broca Maclean
    • 4. The Medial Temporal Lobe and Hippocampus
    • 5. What is amnesia? • Loss of memory function • Two types – Retrograde amnesia • Loss of previously-acquired (”premorbid”) memories – Anterograde amnesia • Inability to form new (”postmorbid”) memories Injury Time
    • 6. (Corkin, Amaral, Gonzalez, Johnson and Hyman J. Neuro, 1997) (Scoville and Milner, 1957) Patient H.M. and the Human MTL • Suffered head injury @age 9 – Developed severe epilepsy • Surgeon surgically removed the medial temporal lobe bilaterally • HM suffered severe anterograde and temporally graded retrograde amnesia • Spared skill learning
    • 7. INTRODUCTION Medial Temporal Circuitry Adjacent MTL cortices : Entorhinal (ERC), Perirhinal (PRC) Parahippocampal (PHC) Hippocampus (HC) proper : Dentate Gyrus (DG), CA3, CA1, and Subiculum (Sub) PRC PHC ERC Sub DG CA 3 CA 1 Fornix
    • 8. Hippocampal Molecular Mechanisms • Place cells, head direction cells, grid cells • Long-term potentiation • Neurogenesis • Microcircuitry
    • 9. Hippocampal Place Cells (O’Keefe & Conway,1978; Wilson & McNaughton, 1993, Ekstrom et al., 2003) Reproduced from Wilson and McNaughton, 1993, Science
    • 10. Place Cells, Head Direction Cells, Grid Cells (Hafting et al., 2005; Moser & Moser, 2007) PRC PHC ERC Sub DG CA 3 CA 1 Fornix
    • 11. Hippocampal Molecular Mechanisms • Place cells, head direction cells, grid cells • Long-term potentiation • Neurogenesis • Microcircuitry
    • 12. Long-Term Potentiation (Kandel et al., 2000, Principles of Neural Science(Kandel et al., 2000, Principles of Neural Science)
    • 13. Long-term potentiation • Bliss & Lomo (1973) discovered that high- frequency stimulation of neurons in the hippocampus results in lasting increase in synapse strength (known as long-term potentiation, or LTP) • LTP relies upon a kind of glutamate receptor (NMDA) • Block LTP – Block Learning
    • 14. Hippocampal Molecular Mechanisms • Place cells, head direction cells, grid cells • Long-term potentiation • Neurogenesis • Microcircuitry
    • 15. Hippocampal Neurogenesis (Li et al., 2000(Li et al., 2000)
    • 16. Exercise-induced increases in Dentate Gyrus CBV correlate with Neurogenesis Pereira A C et al. PNAS 2007
    • 17. Blocking Neurogenesis produces Learning Deficits (Clelland et al., Science, 2009)
    • 18. Taxonomy of Long-term Memory Systems Squire L, Zola S PNAS 1996;93:13515-13522 Adapted from Squire, Knowlton 1994
    • 19. Episodic Learning & Memory Personally experienced events within a spatio-temporal Context (Tulving, 1983, 2002)
    • 20. INTRODUCTION Medial Temporal Circuitry Adjacent MTL cortices : Entorhinal (ERC), Perirhinal (PRC) Parahippocampal (PHC) Hippocampus (HC) proper : Dentate Gyrus (DG), CA3, CA1, and Subiculum (Sub) PRC PHC ERC Sub DG CA 3 CA 1 Fornix
    • 21. Hippocampal Circuits Fornix branch (PostcommisuralBranch) Fornix (Precommissural) (septal-hippocampal pathway) Affects - Theta rhythm (4-8Hz) (Hippocampal commissure) (Perforant & alvear path) Afferents Efferents HIPPOCAMPUS (Cortico-entorhinal projections) ERC/Sub (PHG) Cortex Septal nuclei Mammillary Body Contralateral Hippocampus 1. & 2. 3. 4.
    • 22. The Hippocampus Dentate Complex (HC-DG) Afferent Pathways Pyramidal cell (CA1,2) PHG (ERC, Sub) 1. Perforant Pathway: PHG (ERC) --> DG Also …. 2. Alvear Pathway: PHG --> CA1 3. Septo-hippocampal path (via fornix): Septal nuclei --> DG 4. Hippocampal commissure (connects bilateral hippocampi) Dentate gyrus (granule cells) (mossy fibers) Pyramidal cell (CA3) (schaffer collaterals) 1. (perforant path) (Also note: this efferent path closes the HC circuit loop!) 2. (alvear path) Septal nuclei 3. (septo-hippocampal path - thru fornix)
    • 23. The Hippocampus CA fields A) Lateral Ventricle, B) ependymal glia (ventricular surface), C) Alvear Layer, (pyramidal axons) 3 layers of hippocampus (archicortex): 1. Polymorph Layer (pyramidal axons & basket cells (-)) 2. Hippocampal pyramidal layer (pyramidal cell bodies) 3. Molecular Layer (pyramidal dendrites) A) Lateral ventricle B) Ependymal glia C) Alvear layer 1. Polymorph Layer 2. Pyramidal Layer 3. Molecular Layer(pyramidal dendrite) (pyramidal axon) (pyramidal cell body)
    • 24. Imaging the Human Hippocampus is Challenging
    • 25. High-Resolution Hippocampal Imaging HHR Structural (voxel size = .4 x .4 x 3mm) HHR Functional EPI (voxel size = 1.6 x 1.6 x 3 mm)
    • 26. High-resolution MRI of the MTL (Zeineh, Engel, Thompson, Bookheimer Neuroimage, 2001) (Ekstrom, Bazih, Suthana,(Ekstrom, Bazih, Suthana, Al-Hakim, Ogura, Zeineh, Burggren, Bookheimer. Neuroimag, 2009)
    • 27. Current Research Directions • Encoding vs. Retrieval • Match/Mismatch or Updated Encoding – Allocentric Spatial Encoding • Recollection vs. Familiarity • Pattern Separation / Pattern Completion
    • 28. Face-Name Association Zeineh et al, Science, 2003 Learn Face-Name Pair Covert Name Recall Distractor Learn Recall Learn Recall Learn Recall Learn Recall D D D DRest Rest Time 7 minutes
    • 29. Results
    • 30. Encoding/Retrieval of Spatial Associations (Suthana, Ekstrom, Moshirvaziri, Knowlton, Bookheimer in preparation)(Suthana, Ekstrom, Moshirvaziri, Knowlton, Bookheimer in preparation)
    • 31. Current Research Directions • Encoding vs. Retrieval • Match/Mismatch or Updated Encoding – Allocentric Spatial Encoding • Recollection vs. Familiarity • Pattern Separation / Pattern Completion
    • 32. CA1 region? • Bilateral CA1 damage results in memory impairments (Zola-Morgan et al., 1986; Sass et al., 1995; Rausch & Babb, 1993) • Place cells & computational models (McNaughton & Morris 1987; Lee et al. 2004; Levy 1989; Hasselmo & Schnell, 1994; Blum & Abbot, 1996) PRC PHC ERC Sub DG CA 3 CA 1 Fornix
    • 33. CA1 region? • Bilateral CA1 damage results in memory impairments (Zola-Morgan et al., 1986; Sass et al., 1995; Rausch & Babb, 1993) • Place cells & computational models (McNaughton & Morris 1987; Lee et al. 2004; Levy 1989; Hasselmo & Schnell, 1994; Blum & Abbot, 1996) ERC DG CA 3 CA 1= comparator (match/mismatch detector)
    • 34. EGOCENTRIC (SSP): “Learn store locations relative to starting point” ALLOCENTRIC (MSP): “Learn store locations relative to other stores” Suthana et al., Journal of Neuroscience, 2009 Learning a Cognitive Map (Allocentric Spatial Encoding)
    • 35. (Spearman’s = 0.53, p = 0.02, N=18)ρ Allocentric Egocentric Suthana et al., Journal of Neuroscience, 2009
    • 36. Current Research Directions • Encoding vs. Retrieval • Match/Mismatch or Updated Encoding – Allocentric Spatial Encoding • Recollection vs. Familiarity • Pattern Separation / Pattern Completion
    • 37. Recollection versus Familiarity • (R) Recollection - re-experiencing the encoding event at the time of recall, true episodic memory • (K) - Know - the feeling of familiarity that you’ve seen something before, but not remembering the exact encoding event – Not implicit because it is conscious
    • 38. R vs. K • Eldridge et al have shown the HC is selectively involved in R, not with K. (Eldridge et al., Nature Neuroscience 2000)
    • 39. Current Research Directions • Encoding vs. Retrieval • Match/Mismatch or Updated Encoding – Allocentric Spatial Encoding • Recollection vs. Familiarity • Pattern Separation / Completion
    • 40. – Separation of item/episodic representations – Orthogonolization of sensory input & reduction of interference (Rolls, 1996; Norman & O’Reilly, 2003) Pattern separation & the Hippocampus
    • 41. Felleman & Van Essen (1991)
    • 42. High-res fMRI of Human CA3/DG (Bakker, Kirwan, Miller, and Stark, Science 2008) Hippocampal CA3/DG and Pattern Separation
    • 43. Pattern Separation (CA3/DG) (Clelland et al., Science, 2009) (Leutgeb et al., Science, 2008)
    • 44. Conclusions – Proposed Model (Encoding) PRC PHC ERC DG CA 3 BOLD Neuronal Firing
    • 45. Conclusions – Proposed Model (Retrieval) PRC PHC ERC Sub DG CA 3 CA 1 Fornix BOLD Neuronal Firing
    • 46. Conclusions – Proposed Model (Allocentric / Mismatch Encoding) PRC PHC ERC Sub DG CA 3 CA 1 BOLD Neuronal Firing
    • 47. HC Kluver-Bucy Syndrome Bilateral Amygdala and Pyriform ctx (some area 20 and HC) Subcallosal Gyrus Fornix Cingulate Gyrus Mamillary Bodies Ant. Nucleus PHG Olfactory bulb Septal Nuclei Amygdala
    • 48. *Emotional Response: Endocrine relase, autonomic discharge, facial posturing, body set
    • 49. The brain’s response to seeing emotional faces • Face-specific brain region (fusiform face area) • Seeing emotional faces (fear, anger) increases activity in the emotional system (amygdala) • No conscious perception is required • Frontal lobes can control this response
    • 50. Single Neuron Recordings in Humans
    • 51. (Quian Quiroga Reddy, Kreiman, Koch, & Fried. Nature, 2005) (Waydo, Kraskov, Quian Quiroga, Fried, & Koch. Journal of Neurosci 2006) Invariant Representations in the Human MTL
    • 52. Improved Electrode Localization Improved electrode localization and targeting using high- resolution imaging and cortical unfolding (Ekstrom, Suthana, Behnke, Bookheimer, and Fried, Journal of Neurosurgery, 2009)(Ekstrom, Suthana, Behnke, Bookheimer, and Fried, Journal of Neurosurgery, 2009)
    • 53. Target Lure 1 Lure 2 Lure 3 Lure 4 Pattern Separation in Human CA3/DG Suthana et al., in preparation

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