The main purpose of this thesis is to present empirical evidences for temporal coding in the hippocampus. The current theories of temporal coding in relationship to other coding hypotheses will be reviewed in the first chapter. Here, I will articulate a set of hypotheses which are testable on parallel spike trains. In order to convey my arguments for the presence of higher order statistics in parallel spike trains, I describe a whole scaffold of methods from extracellular unit identification to significance testing on sequence repetition. Since reliable identification of the extracellular signal with single cell action potentials is a prerequisite to investigate the hidden temporal structure of a parallel spike trains, the second chapter is dedicated to discuss problems and solutions of the multiple single unit analysis. The third chapter is dedicated to present empirical evidence for the existence of invariant spatio-temporal pattern of spikes (sequences) in the parallel spike trains, recorded simultaneously from multiple pyramidal cells of the hippocampus, during successive episodes of sleep and wheel running behaviors.

The music of the neurons. The activity of seven pyramidal cells and one interneuron recorded from the CA1 area of the hippocampus was converted to a piano play by assigning different neurons to different keys of a harmony. Each note represents a spike of that neuron and the timing of the note corresponds to the time of occurrence of the action potential.
 

Introduction

TEMPORAL COIZE=-1>Introduction

TEMPORAL CODING AND ANALYSIS OF SPIKE SEQUENCES

BACKGROUND 1

Models of Neuronal Coding 1

Frequency Coding 2

Temporal Coincidence Coding 5

From Synchronization to Temporal Coordination 6

External Drive of Spike Sequences 8

The Replay Hypothesis 9

Internally Generated Sequences 10

Spatio-Temporal Coding 10

Conceptual Models Of The Hippocampus In Relationship To Temporal Coding 12

Empirical Support for the Temporal Coding Hypothesis 14

Local Theta and Gamma Activity in Relationship to Multiunit Activity 17

Sharp-Wave and Fast Field Oscillation (Ripples) in Relationship to Multiunit Activity 19

Similarities Between Gamma and Ripple Activity 19

HYPOTHESES 20

Hypothesis 1: The temporal positions of spikes are not random 20

Hypothesis 2: Individual neurons can be independent parts of multiple cell assemblies 22

Hypothesis 3: Spike sequences tend to co-occur with large field events (theta, sharp waves) 23

Hypothesis 4: Sequences detected during theta activity will recur and be identifiable during subsequent sharp wave episodes 24

Conceptual Background for Analyzing the Temporal Structure of Spikes 25

The insufficiency of cross-correlation method in the assessment of functional connectivity 25

The Pnnectivity 25

The Poisson surprise function 30

Monte Carlo Statistics on Surrogate Data 30

Methods

EXTRACELLULAR RECORDING AND ANALYSIS OF NEURONAL ACTIVITY

THE NEED FOR HIGH RESOLUTION IMAGING OF NETWORK ACTIVITY 33

SLOW FIELDS AND UNIT ACTIVITY: THE SOURCE OF EXTRACELLULAR CURRENT FLOW 34

EXTRACELLULAR RECORDING OF ACTION POTENTIALS 37

Spike Propagation in the Extracellular Space 38

Active Backpropagation of Action Potentials in Dendrites: Origin of Complex-spike Bursts 39

Sources of Amplitude- and Shape-variations of the Extracellular Unit 42

Cell Lipid Membrane - Capacitive Differentiation 42

Membrane Potential 43

Dendritic Morphology 44

Dendritic Spike Generation 47

Evoked Unit Responses 48

Properties Of Extracellular Space 51

MULTIPLE SITE SILICON PROBES FOR PARALLEL RECORDING OF UNIT AND FIELD ACTIVITIES 51

SINGLE CELL IDENTIFICATION IN PARALLEL-RECORDED MULTIUINT RECORDINGS 53

Spatial Localization of Electrical Sources: Field Potentials 55

Spatial Localization of Electrical Sources: Extracellular Units 59

Clustering and its problems 62

Post-hoc Tests and Reclustering 64

Effect of Sampling Frequency and Spike Reconstruction 65

EXPERIMENTAL PROCEDURES 66

METHODS OF SPIKE SEI>

METHODS OF SPIKE SEQUENCE DETECTION 68

HISTOLOGICAL PROCEDURES 77

Results

RECURRING SPIKE SEQUENCES IN HIPPOCAMPAL PYRAMIDAL CELLS IN THE AWAKE AND SLEEPING RAT

Sequence Detection By Template Matching Method 78

Comparison of Original and Shuffled Spike Trains by Monte Carlo Simulation 82

Spike Sequences Detected by The Joint Probability Map Method 85

Behavioral Modulation of Spike Sequences 92

Discussion

SEQUENCES VS. BY CHANCE COINCIDENCES OF SPIKES 96

EXTERNALLY CONTROLLED AND INTERNALLY GENERATED RECURRING SPIKE SEQUENCES 99

TEMPORAL COORDINATION AND SEQUENCE REPETITION 100

RECURRING SPIKE SEQUENCES: DO THEY HAVE A PURPOSE? 103

References

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