# Neuromodulation of Neuronal Oscillations

> **NIH NIH R01** · NEW JERSEY INSTITUTE OF TECHNOLOGY · 2020 · $375,546

## Abstract

Neuromodulators provide flexibility for neural circuit operation and behavior. Yet, at any given time, neural
circuits are subject to modulation by multiple neurotransmitters and neurohormones. Each modulator elicits its
own specific activity pattern, and presumably, co-modulation by multiple substances increases the degree of
circuit flexibility. Despite the multitude of possible combinations and relative concentrations, the output of any
neural circuit has low variability across individuals under baseline conditions. Even under identical modulatory
conditions this would not be obvious, given that the expression levels of the molecular targets of modulators,
for example ion channels, can vary substantially across the population. Numerous studies show that multiple
modulators can target the same voltage-gated ion channel type or the same synapse. We propose, somewhat
counterintuitively, that the presence of multiple convergent neuromodulators at low concentrations in fact
reduces population variability of circuit activity, a hypothesis that is supported by preliminary data. We further
propose that consistent circuit activity can occur in the presence of different sets of convergent modulators.
We examine these hypotheses in the oscillatory pyloric circuit of the crab stomatogastric ganglion (STG), one
of the premier systems for the study of neuromodulation. We propose to combine detailed quantitative
measurements of circuit output, as well as underlying synaptic and voltage-gated ionic currents, at different
concentrations of 5 neuropeptide modulators and a muscarinic agonist. The modulators of interest are known
to target the same fast low-threshold voltage-gated inward current, which increases excitability of STG
neurons. A subset of the peptide modulators are known to enhance the same synaptic connections, while
others have unknown actions on the synapses, which we plan to explore. Electrical coupling conductances
also appear to be modulated by the peptides, potentially with nonlinear interactions. We propose experiments
to examine the interactions of modulators at these component levels, with a detailed focus on two well studied
neuropeptide modulators, proctolin and the crustacean cardioactive peptide.
We will use evolutionary algorithm optimization techniques to produce populations of computational models of
the pyloric neurons and synapses, based on these data, where each single model produces the same
responses, but different models in the population have different levels of ionic conductances, as observed in
the biological system. Component models will be used to build circuit models that produce appropriate activity
and correct (co-)modulatory responses. These models would allow us to explore how circuit-level population
variability may be changed by co-modulation and by component variability. Additionally, the models will enable
us to predict how modulation of components gives rise to circuit patterns of activity specific to that modul...

## Key facts

- **NIH application ID:** 9852344
- **Project number:** 5R01MH060605-18
- **Recipient organization:** NEW JERSEY INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Dirk Martin Bucher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,546
- **Award type:** 5
- **Project period:** 2000-12-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852344

## Citation

> US National Institutes of Health, RePORTER application 9852344, Neuromodulation of Neuronal Oscillations (5R01MH060605-18). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852344. Licensed CC0.

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