# The role of medial striatum in spatial sequence learning

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $431,750

## Abstract

The hippocampus (HPC) encodes concomitantly current, past and future locations; and distinguishes between
events that occur in the same place as part of distinct experiences. These aspects of HPC activity are likely to
support episodic memory, which encodes personally experienced past events. However, the neural substrate
that supports the use of these episodic memories to achieve flexible behavior remains insufficiently
understood, precluding thus the development of treatments in memory disorders. One way in which memory-
based flexible behavior may be generated is by transient coordination of activity between HPC and other local
memory networks such as dorso-medial striatum (DSM) which is involved in behavioral flexibility and whose
neurons fire in action-modulated manner (action choice, AC). The long-term goal of this line of research is to
understand how circumstantial mnemonic demand may lead to transient functional coupling of distinct local
memory circuits in order to guide behavior (the dynamic model of memory). The objective of the current
proposal is to evaluate the contribution of DSM to disambiguation of repeated traversals of the same physical
spatial locations while on distinct journeys (sequential context), a task relevant for HPC function and episodic
memory. The central hypothesis of the current proposal is that the structure of the behavioral task modulates
how similar events that occur in the same space are distinguished as part of different episodes in the HPC-DSM
network. The rationale of the proposed work is that a determination of how neural circuits use stored
information to act adequately in similar but yet distinct circumstances will offer a strong scientific framework
whereby new strategies in memory research can be developed.. We propose the following two specific aims:
Aim 1. Identify the roles of HPC and DSM activities in disambiguation of sequential contexts.
The working hypothesis of this aim is that a combination of neural firing in both HPC and DSM is necessary to
successfully distinguish the extended spatial sequences that share segments of trajectory. Aim 2. Identify
the HPC/DSM neural activity patterns that are correlated with successful disambiguation of
sequential contexts Our working hypothesis is that although HPC does not differentiate between sequential
contexts at the second scale, distinction is made at the millisecond scale in place cells' activity in combination
with the activity of DSM neurons which encode AC. We expect the results of the proposed research to
demonstrate that that disambiguation of sequential contexts involves a neural network encompassing both
HPC and DSM (Aim 1); and that analyzing the deep structure of neural activity will uncover how the HPC
representation combines with DSM activity to guide behavior when appropriate action involves memory of
distinct past events that occurred in the same environment (Aim 2). The results of the proposed research will
contribute to fully understa...

## Key facts

- **NIH application ID:** 10727401
- **Project number:** 1R21MH134182-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Janina Diana Ferbinteanu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $431,750
- **Award type:** 1
- **Project period:** 2023-09-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10727401

## Citation

> US National Institutes of Health, RePORTER application 10727401, The role of medial striatum in spatial sequence learning (1R21MH134182-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10727401. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*