Amygdala Stimulation Enhances Memory for Specific Events by Modulating the Hippocampus Open Access

Bass, David Ian (2014)

Permanent URL: https://etd.library.emory.edu/concern/etds/ms35t909p?locale=en
Published

Abstract

Prioritization of information into long-term memory is essential for survival. Emotional arousal enhances memory for these events, and this emotional enhancement of memory is mediated by the amygdala. The amygdala has projections to many regions throughout the brain, including the hippocampus, a structure that supports memory for events. The goal of the research discussed in the present dissertation is to understand how the amygdala modulates the hippocampus in the service of enhancing memory. Characterizing the interaction between these two structures is fundamental to understanding how important information is prioritized for consolidation. Furthermore, a deeper understanding of this physiological interaction will further our understanding of the pathophysiology driving affective disorders, such as post-traumatic stress disorder. To address this goal, we developed an object recognition memory task to test memory for specific events in rats and demonstrated that brief electrical stimulation to the basolateral complex of the amygdala (BLA) selectively enhanced memory in a stimulus-specific manner when memory was tested 1 day later. In a follow-up study, we demonstrated that amygdala-mediated enhancement of memory for specific events depends on the hippocampus. Finally, we obtained recordings of local field potentials and spiking activity in the hippocampus from rats that received amygdala stimulation while performing the memory task. Data analysis took advantage of the ipsilateral connectivity between the BLA and the hippocampus by contrasting ipsilateral and contralateral stimulation. The results indicate that ipsilateral BLA stimulation elicits low gamma coherence between CA3 and CA1. Stimulation did not have a substantial impact on the firing rate of pyramidal unit populations, but ipsilateral stimulation induced a strong phase preference of CA3 pyramidal spikes relative to low gamma oscillations in the local field potential of CA1. Thus, the main effect of BLA stimulation on hippocampal pyramidal units was via modulation of spike timing. Correlations between improved memory and intra-hippocampal synchronization have previously been reported, but this is study is unique in that gamma synchronization was induced to enhance memory.


Table of Contents

Chapter 1. Introduction: Background & Motivation

1.1 The Amygdala, the Hippocampus, and Memory. 2

1.1.1 Prioritization of memory. 2

1.1.2 Memory systems. 3

1.1.3 Review of amygdala and hippocampal anatomy. 6

1.1.4 Amygdala and hippocampal dysfunction in affective disorders. 9

1.2 The Novel Object Recognition Memory Task. 10

1.2.1 Initial conception. 10

1.2.2 A novel paradigm for testing memory for specific events in rats. 11

1.3 Neural Oscillations and Plasticity. 12

1.3.1 Local field potentials. 12

1.3.2 Gamma oscillations in memory. 14

1.4 Rationale for Electrophysiology. 15

1.5 Specific Aims. 16

Chapter 2. Event-Specific Enhancement of Memory via Brief Electrical Stimulation to the Basolateral Complex of the Amygdala in Rats. 24

2.1 Abstract 25

2.2 Introduction. 26

2.3 Method. 28

2.3.1 Subjects. 28

2.3.2 Surgery. 28

2.3.3 Electrical Stimulation. 29

2.3.4 Novel Object Recognition Memory Task. 29

2.3.5 Histology. 30

2.3.6 Data Analysis. 31

2.4 Results. 32

2.5 Discussion. 33

Chapter 3. Amygdala-Mediated Enhancement of Memory for Specific Events Depends on the Hippocampus 41

3.1 Abstract 42

3.2 Introduction. 43

3.3 Method. 44

3.3.1 Subjects. 44

3.3.2 Surgery. 45

3.3.3 Electrical stimulation and muscimol infusions. 45

3.3.4 Object recognition memory testing. 46

3.3.5 Histology. 47

3.3.6 Video scoring and behavioral data analysis. 48

3.4 Results. 48

3.4.1 Histology and subject exclusion. 48

3.4.2 Object recognition memory performance. 49

3.5 Discussion. 52

Chapter 4. Memory-Enhancing Electrical Stimulation of the Amygdala Elicits Gamma Band Synchronization between CA3 and CA1 in the Hippocampus. 61

4.1 Abstract 62

4.2 Introduction. 63

4.3 Method. 64

4.3.1 Subjects. 65

4.3.2 Novel object recognition memory task. 65

4.3.3 Surgery and tetrode positioning. 66

4.3.4 Electrical stimulation. 67

4.3.5 Histology. 68

4.3.6 Data acquisition and analysis. 69

4.4 Results. 74

4.4.1 Histology and Subject Exclusion. 74

4.4.2 Robust increase in low gamma coherence during exploration. 76

4.4.3 Evoked responses in the LFP are visible as oscillations in the low gamma range. 76

4.4.4 Ipsilateral BLA stimulation elicits low gamma synchronization. 77

4.4.5 BLA stimulation does not substantially impact firing rate. 80

4.4.6 Ipsilateral BLA stimulation elicits spike-phase preferences in low gamma range. 82

4.4.7 Ipsilateral stimulation may induce recent exploration-related patterns of spiking activity 85

4.5 Discussion. 86

Chapter 5. Discussion. 116

5.1 Conclusions. 117

5.1.1 Summary of Results and Interpretations. 117

5.1.2 Alternate Interpretations. 120

5.2 Methodological Considerations. 122

5.3 Future Directions. 125

5.4 Clinical Translation. 129

5.4.1 Implications. 129

5.4.2 Applications. 130

References. 133

About this Dissertation

Rights statement
  • Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.
School
Department
Subfield / Discipline
Degree
Submission
Language
  • English
Research field
Keyword
Committee Chair / Thesis Advisor
Committee Members
Last modified

Primary PDF

Supplemental Files