# LRRK2 mediated corticostriatal plasticity events in the striatum

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $77,132

## Abstract

Project Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disease of aging. Mutations in LRRK2
are associated with both inherited and sporadic forms of PD. LRRK2 is highly enriched in spiny projection
neurons (SPN) in the dorsal striatum. However, the physiological role of LRRK2 in SPNs remains elusive. Our
previous observations suggest a linkage between the pathogenic R1441C mutation and aberrant PKA signaling
in SPNs. However, the analyses were limited by the inherent resolution provided by conventional biochemical
approaches and microscopy. Here, we seek to provide more precise information about the pathophysiological
consequences of LRRK2 mutations in SPNs. In particular, it is our central hypothesis that LRRK2R1441C mutation
leads to aberrant dopaminergic signaling in SPNs. The resultant striatal dysfunction, in turn, contributes to the
symptomatology of PD. Given that among the most significant changes that occur during the disease progress
is the imbalance of corticostriatal plasticity, we will examine if LRRK2 mutations alter corticostriatal plasticity,
through PKA and dopamine signaling dysregulation. These data will be integrated with our findings on striatal-
dependent motor learning in a whole-animal setting in order to establish that the motor learning impairment is a
phenotypic outcome of dopamine-dependent LRRK2’s role on plasticity. In conjunction with standard cellular,
molecular, and electrophysiological approaches, our investigations will capitalize on a combination of cutting-
edge approaches that overcome obstacles that have impeded progress to date. These include, knock-in LRRK2
mutant mice, striatal pathway-specific reporter mice, and viral gene delivery. The successful achievement of
these studies will significantly advance our understanding of the molecular mechanisms underlying corticostriatal
plasticity in PD, and in doing so, will promote the development of new therapies for PD patients in the future.

## Key facts

- **NIH application ID:** 10227318
- **Project number:** 3R01NS097901-05S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Loukia Parisiadou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $77,132
- **Award type:** 3
- **Project period:** 2016-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227318

## Citation

> US National Institutes of Health, RePORTER application 10227318, LRRK2 mediated corticostriatal plasticity events in the striatum (3R01NS097901-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10227318. Licensed CC0.

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