Associative Learning and the Monkey Medial Temporal Lobe
Associative Learning and the Monkey Medial Temporal Lobe Wendy A. Suzuki Center for Neural Science New York University
Ventral View of Macaque Monkey Brain PH PR ER rs
AP 14. 5 L R HPC EC PR
30 -60% 18 -29% 5 -17% <5% DG HPC Sub Entorhinal Perirhinal 46 11/12 13 Parahippocampal Pi TE STSv Ia STSd STG TEO 24/25/32 7 a/LIP Id Ig 23/29/30 V 4 Frontal Lobe Suzuki and Amaral, 1994 Temporal Lobe Insular Cortex Cingulate Gyrus Parietal Lobe
Experimental Question: What are the neural correlates of associative memory formation in the medial temporal lobe?
Location-Scene Association Task Gaffan (1994) Murray and Wise (1996) Murray et. al. , (1998)
Location-scene association task New Scenes (n = 2 -4) + + + Reference Scenes n=4 + + + Scene/Target Presentation (500 ms) Delay (700 ms) Fixation/ Baseline (300 ms) Eye Movement Response
Working Hypothesis Selective changes in the patterns of activity in hippocampal neurons underlie the formation of new location-scene associations.
Response to 3 New Scenes + + + Baseline Scene/Target Delay EM 45 40 Spikes/Sec 35 30 25 20 15 10 5 0 -300 0 500 Time from Scene Onset (ms) 1200 C 110600
1 50 0. 8 40 30 0. 6 20 0. 4 10 0. 2 Baseline Activity 0 0 10 20 30 Trials 40 50 0 Response (Spikes/Sec) Probability Correct Behavioral Learning Curve and Delay Activity Over Time to Scene 653 -10 C 110600. 4
1 50 0. 8 40 30 0. 6 20 0. 4 10 0. 2 0 0 0 21 Trials 41 Response (Spikes/Sec) Probability Correct Behavioral Learning Curve and Delay Activity Over Time for Reference Scene 67 -10 C 110600. 4
Are There Different Categories of Changing Cells?
2 Categories of Changing Cells A. Sustained Changing cells: 56% of all changing cells B. Baseline Sustained Changing cells: 44% of all changing cells
1 50 0. 8 40 30 0. 6 20 0. 4 10 0. 2 Baseline Activity 0 0 10 20 30 Trials 40 50 0 Response (Spikes/Sec) Probability Correct Behavioral Learning Curve and Delay Activity Over Time to Scene 653 -10 C 110600. 4
Categories of Changing Cells A. Sustained Changing cells: 56% of all changing cells B. Baseline Sustained Changing cells: 44% of all changing cells
Behavioral Learning Curve and Delay Activity Over Time to Scene 386 16 14 12 10 8 6 4 2 0 0. 8 0. 6 0. 4 0. 2 0 1 4 7 10 13 16 19 22 25 28 31 34 37 Trials Response (Spikes/Sec) Probability Correct 1
Categories of Changing Cells A. Sustained Changing cells: 56% of all changing cells B. Baseline Sustained Changing cells: 44% of all changing cells
What Does the Change in Neural Activity Represent?
Degree of selectivity was measured Using a selectivity Index (Moody et al. , 1989) n is the total number of scenes λi is response to ith scene λmax is maximal response for a cell
Measures of Selectivity: Sustained Changing Cells 0. 7 * Selectivity Index 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0 Before After Learning
Response of a changing cell to all scenes 1 Ref 2 Ref 3 12 10 Ref 4 New 1 New 2 0. 8 0. 6 8 Learning Curve 6 0. 4 4 0. 2 2 0 1 11 21 31 41 51 61 Trials 71 81 0 91 101 111 Probability Correct Response (Spikes/Sec) 14
Measures of Selectivity: Baseline Sustained Changing Cells 0. 8 * 0. 7 Selectivity Index 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0 Before After Learning
What is The Time Course of the Changing Cells relative to Learning?
1 50 0. 8 40 30 0. 6 20 0. 4 10 0. 2 Baseline Activity 0 0 10 20 30 Trials 40 50 0 Response (Spikes/Sec) Probability Correct Behavioral Learning Curve and Delay Activity Over Time to Scene 653 -10 C 110600. 4
Neural Change vs. Learning Neurons that change after learning Neuronal Change 50 40 30 Neurons that change before learning 20 10 0 0 10 20 30 40 Behavioral Change 50
Ratio Index Before – After Ratio Index = Before + After
Ratio Index: Hippocampus 1. 5 Ratio Index 1 0. 5 0 -0. 5 -1 -1. 5 1 - 10 11 - 20 21 - 30 Trials to Learn > 31
Where are the changing cells located?
Hippocampal Recording Sites AP 14. 0 -6 Dorsoventral -8 Monkey 1 Sustained Baseline Sustained Selective Nonresponsive/nonselective -10 -12 -14 -16 -18 20 18 16 14 12 Anteroposterior 10 8
Summary Hippocampal Changing Cells: 1. Signal new learning with changes in their stimulusselective response properties 2. Participate throughout the early learning process 3. Are located throughout the hippocampal region
2. Comparison with the Perirhinal Cortex
30 -60% 18 -29% 5 -17% <5% DG HPC Sub Entorhinal Perirhinal 46 11/12 13 Parahippocampal Pi TE STSv Ia STSd STG TEO 24/25/32 7 a/LIP Id Ig 23/29/30 V 4 Frontal Lobe (Suzuki and Amaral, 1994) Temporal Lobe Insular Cortex Cingulate Gyrus Parietal Lobe
Hippocampus PR Cortex (n = 2 monkeys) Selec tive 89/145 (61 %) 67/104 (64 %) 25/89 (28%) 19/67 (28%) Sustained 14/25 (56%) 4/19 (21%) Baseline Sustained 11/25 (44%) 15/19 (79%) Changing Cells
Learning-related cells in the Perirhinal Cortex Baseline Sustained Changing Cell 60 1. 0 25 1. 0 r= -0. 62 0. 8 50 0. 6 40 0. 4 30 0. 0 20 30 Trial Number 0. 6 0. 4 15 0. 2 r= 0. 58 10 20 40 10 0. 0 10 20 30 Trial Number 40 Probability Correct Response (Spikes/Sec) Sustained Changing Cell
What is The Time Course of the Changing Cells relative to Learning?
Hippocampus Perirhinal Cortex Behavioral Change
Ratio Index: Hippocampus 1. 5 Ratio Index 1 0. 5 0 -0. 5 -1 -1. 5 1 - 10 11 - 20 21 - 30 Trials to Learn > 31
Ratio Index: Hippocampus vs. PR 1. 5 Perirhinal Hippocampus Ratio Index 1 0. 5 0 -0. 5 -1 -1. 5 1 - 10 11 - 20 21 - 30 Trials to Learn > 31
Hippocampus Perirhinal Cortex Behavioral Change
Location-scene association task: Within Trial Analysis New Scenes + + + Fixation Scene/Target Delay Response
Within-Trial Analysis: Sustained Cells Fixation Scene Delay + Response + Normalized Response 0. 8 Perirhinal Hippocampus 0. 6 0. 4 0. 2 0. 0 -0. 2 0 200 400 600 800 1000 1200 1400 1600 1800 Time (ms)
Within-Trial Analysis: Baseline Sustained Cells Fixation Scene Delay + Response + Normalized Response 1. 0 Perirhinal Hippocampus 0. 8 0. 6 0. 4 0. 2 0. 0 -0. 2 0 200 400 600 800 1000 1200 1400 1600 1800 Time (ms)
Hippocampus Perirhinal Cortex Behavioral Change
Learning Signals Across the Brain Hippocampus Perirhinal Cortex Cahusac et al. , 1993 Wirth et al. , 2003 Yanike et al. 2005 SEF & FEF Premotor Cortex Chen and Wise, 1995 a, b Mitz et al, 1991 Brasted and Wise, 2004 Striatum Prefrontal Cortex Brasted and Wise, 2004 Asaad et al. , 1998
Neural Change vs. Learning Neurons that change after learning Neuronal Change 50 40 30 Neurons that change before learning 20 10 0 0 10 20 30 40 Behavioral Change 50
Population Response: Sustained cells 0. 7 Proportion 0. 6 0. 7 PM Putamen HPC (Cahusac) 0. 6 SEF 0. 5 0. 4 0. 3 0. 2 0. 1 0 0 Lead Same Time HPC (Wirth) Lag HPC (Wirth/Wise) Lead Same Time Neural activity relative to behavior Lag
Population Response: Sustained cells 0. 7 Proportion 0. 6 0. 7 PM Putamen HPC (Wirth) HPC (Cahusac) 0. 6 SEF HPC (Wirth/Wise) 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0 0 0 Lead Same Time Lag Lead Same Time Perirhinal Lag Neural activity relative to behavior Lead Same Lag Time
30 -60% 18 -29% 5 -17% <5% DG HPC Sub Entorhinal Perirhinal 46 11/12 13 Parahippocampal Pi TE STSv Ia STSd STG TEO 24/25/32 7 a/LIP Id Ig 23/29/30 V 4 Frontal Lobe (Suzuki and Amaral, 1994) Temporal Lobe Insular Cortex Cingulate Gyrus Parietal Lobe
Summary HPC and PR exhibit similar proportions and categories of changing cells. HPC and PR exhibit a similar temporal relationship between learning and neural activity PR signals learning during the scene period of the task while the HPC signals learning during the delay
Sylvia Wirth Marianna Yanike
Suzuki Laboratory Postdoctoral Fellows Students Emin Avsar Eric Hargreaves Sylvia Wirth Marianna Yanike Technicians Emery N. Brown Loren M. Frank Anne C. Smith Cindy Chiu Stephen Leonard Nilda Nystrom Collaborators
30 -60% 18 -29% 5 -17% <5% DG HPC Sub Entorhinal Perirhinal 46 11/12 13 Parahippocampal Pi TE STSv Ia STSd STG TEO 24/25/32 7 a/LIP Id Ig 23/29/30 V 4 Frontal Lobe Suzuki and Amaral, 1994 Temporal Lobe Insular Cortex Cingulate Gyrus Parietal Lobe
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