# Electrogenic Modulation of Signal Decoding in Presynaptic Terminals

> **NIH NIH P20** · DARTMOUTH COLLEGE · 2020 · $351,657

## Abstract

Presynaptic terminals are fundamental computational units in the brain, and their dysfunction is associated 
with several neurological diseases. They mediate the transduction of incoming electrical signals (action 
potentials) into chemical signals (neurotransmitter release), and the efficiency of conversion determines the 
strength of circuits underlying memory and behavior. The ultimate goal of this proposal is to understand the 
mechanisms by which presynaptic cellular machineries modulate the electro-chemical transduction of action 
potentials. It is known that presynaptic terminals are highly adaptive structures capable of maintaining 
transmission across vastly different input rates, metabolic states, and vesicle fusion probabilities. Our recent 
work in combination with others has exposed the fact that action potentials are not invariant signals. One 
critical level of regulation exists within the axonal arborization, which actively regulates the propagation and 
shape of electrical signals arriving at each of its presynaptic terminals. We hypothesize that a second 
complementary, but currently uncharacterized, set of mechanisms exist at presynaptic terminals that rapidly 
sense the cellular state and alter the chemical transduction of electrical signal inputs. As a result, the 
individual presynaptic terminals instantaneously adjust the electrogenic properties of their membranes 
through local ion channel activation pathways which dynamically regulate the chemical response to a given 
action potential as it arrives. We propose to identify the molecular basis of this “on the fly” control system of 
transduction in the following aims: Aim 1. We will determine how the cellular metabolic energy state of the 
synapse (ATP:ADP ratio) influences action potential transduction via ATP-sensitive potassium channels. Aim 
2. We will determine how stimulation frequency alters the activation of presynaptic voltage- and calciumsensitive 
potassium channels to influence action potential transduction in excitatory and inhibitory terminals. 
Aim 3. We will determine how coupling calcium channels to vesicle fusion release machinery controls 
potassium channel activation. Results from these aims will present new data on electrogenic mechanisms 
influencing complex computations of presynaptic terminals, leading to a more complete understanding of 
synaptic plasticity and neuronal processing.

## Key facts

- **NIH application ID:** 10215732
- **Project number:** 5P20GM113132-05
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Michael Blake Hoppa
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $351,657
- **Award type:** 5
- **Project period:** 2018-03-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215732

## Citation

> US National Institutes of Health, RePORTER application 10215732, Electrogenic Modulation of Signal Decoding in Presynaptic Terminals (5P20GM113132-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10215732. Licensed CC0.

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