# Administrative Supplement (Diversity) to Molecular Mechanisms Governing the Homeostatic Control of Synaptic Strength

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $111,058

## Abstract

PROJECT SUMMARY
Stable functionality in the nervous system is maintained despite the challenges associated with
development, growth, experience, aging, and disease. This remarkable stability is controlled by
potent and adaptive homeostatic signaling systems that sustain robust and reliable information
transfer across synapses. Synapses are therefore critical substrates to achieve and maintain the
homeostatic control of neural activity. Indeed, homeostatic synaptic plasticity is fundamental form
of plasticity endowed at synapses in the central and peripheral nervous systems of invertebrates,
rodents, and humans. Defects in homeostatic signaling contribute to the etiology of a variety of
neurological diseases including epilepsy, Fragile X Syndrome, and neurodegeneration. However,
the molecular mechanisms that induce and sustain homeostatic plasticity remain enigmatic. To
understand synaptic dysfunction during disease states, we must first decipher the intercellular
dialogue that controls homeostatic signaling.
 Our long-term goals are to define the mechanisms that achieve and maintain the homeostatic
control of synaptic function in health and disease. Towards this end, we have pioneered forward
genetic screens using electrophysiology that have discovered new genes and revealed
fundamental mechanisms mediating homeostatic signaling at the Drosophila neuromuscular
junction. At this model glutamatergic synapse, acute pharmacological inhibition or chronic genetic
elimination of postsynaptic glutamate receptors (GluRs) triggers a retrograde signaling system in
the postsynaptic compartment that precisely increases presynaptic neurotransmitter release to
maintain stable synaptic strength. This process is referred to as Presynaptic Homeostatic
Potentiation (PHP). Work from the Dickman lab and others have uncovered many presynaptic
genes that converge on two key mechanisms that serve to increase neurotransmitter release and
enable the expression of PHP. In addition, candidate retrograde signals have also been identified.
In contrast to the emerging framework from which we now understand how enhanced presynaptic
neurotransmitter release is controlled following PHP expression, almost nothing is known about
the signaling system in the postsynaptic compartment that senses diminished GluR function and
transforms this into tunable information transmitted to specific presynaptic compartments.
Therefore, illuminating the nature of the postsynaptic induction mechanisms that initiate and
maintain PHP will be the primary goal of this proposal. In this supplement, we propose to
investigate the function of two newly identified postsynaptic genes, peflin and ALG2, in retrograde
homeostatic signaling.

## Key facts

- **NIH application ID:** 10062396
- **Project number:** 3R01NS091546-06S1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** DION KAI DICKMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $111,058
- **Award type:** 3
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062396

## Citation

> US National Institutes of Health, RePORTER application 10062396, Administrative Supplement (Diversity) to Molecular Mechanisms Governing the Homeostatic Control of Synaptic Strength (3R01NS091546-06S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10062396. Licensed CC0.

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