# Mechanisms of expression and relationship between two distinct types of internally generated hippocampal sequences

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $405,000

## Abstract

PROJECT SUMMARY/ABSTRACT
 The brain expresses several distinct types of internally generated sequences of neuronal activity
independent of external sensory stimuli, and such temporally precise, self-organized sequences play a crucial
role in information processing and memory formation/retrieval. In particular, the hippocampus generates two
separate, well-defined forms of neuronal sequences: sharp-wave/ripple (SWR)-associated sequences which
are observed during “off-line” states such as rest or sleep, and theta-associated sequences which occur during
“on-line” states such as active exploration. Prior work has demonstrated a link between SWR sequences and
working memory, long-term memory, and future planning, while theta sequences have been associated with
decision-making and immediate future behaviors. However, little is known regarding how these two sequence
types interact with experience or each other to facilitate mnemonic processes. Further, the circuit mechanisms
which allow specific neuronal activity patterns to be expressed within internally generated sequences are
largely unknown. The central objective of this study is to utilize ultra-high density, large-scale in vivo
electrophysiology coupled with complex spatial navigational tasks to examine in depth these two forms of
sequential activity to identify fundamental principles which underlie their generation, function, and relationship
to each other. Supported by considerable preliminary data, we propose to pursue this objective through three
specific aims: (1) To define the relationship between internally generated sequences and ongoing behavior
during periods of memory formation vs. memory retrieval/use; (2) To determine the mechanisms underlying
development, persistence, and function of internally generated sequences in sleep; (3) To identify how the
patterns and weights of connectivity within the hippocampus contribute to the expression and propagation of
internally generated sequences. Together, this study is expected to meaningfully advance our understanding
of circuit-level brain function by revealing the fundamental principles which allow precise patterns of activity to
be dynamically generated and propagated throughout the hippocampal network in support of learning.

## Key facts

- **NIH application ID:** 9840524
- **Project number:** 5R01NS104829-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** BRAD E PFEIFFER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840524

## Citation

> US National Institutes of Health, RePORTER application 9840524, Mechanisms of expression and relationship between two distinct types of internally generated hippocampal sequences (5R01NS104829-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9840524. Licensed CC0.

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