# Imaging neuromodulation in the brain

> **NIH NIH R37** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2022 · $391,704

## Abstract

Addiction involves brain systems mediating internal states of motivation, arousal and reward, as well as
emotions. Such internal states influence goal-directed behaviors and decision-making. A common feature of
such internal states is their valence and their persistence: they can have a positive or negative valence, and
can outlast their triggering stimulus for many minutes. However the neurobiological mechanisms that underlie
the persistence of internal states, and their relationship to the encoding of valence, are poorly understood.
 Drosophila provides a tractable genetic model organism for studying how neuromodulators act on neural
circuits to control persistent internal states that govern goal-directed behavior and decision-making. We have
discovered that P1 interneurons, which control male courtship behavior, can when activated promote a
persistent internal state of social arousal or motivation, which can last for minutes. In a publication supported
by the base grant, we have obtained evidence of a link between P1 interneurons and neurons that respond to
octopamine (OA), an insect homolog of norepinephrine (NE), which is known to facilitate psychostimulant self-
administration in rodents. We have also identified a downstream target of P1 neurons, called pCd cells, which
appear to play a key requisite role in determining the persistence of an internal state of social arousal.
 During the extension period, we will continue our studies of how P1 neurons promote a rewarding internal
state, and the relationship of these mechanisms to the positive valence, or rewarding nature, of P1 stimulation.
In the first 2 years, we will focus on pursuing Aims 3 and 4 of the base grant. These aims were: Aim 3) to test
the hypothesis that P1 neuron activation is positively valenced and rewarding; Aim 4) to investigate
neuromodulatory mechanisms involved in P1 reward learning. In unpublished experiments, we have
discovered that activation of P1 neurons can produce a real-time place preference (RTPP), and that it can also
serve as an unconditional stimulus (US) for conditioned olfactory preference (COP). Both of these findings
indicate that P1 activation is positively valenced, and that it can be rewarding. We plan to investigate whether
plasticity during COP occurs at or downstream of P1 neurons, and whether P1 neurons are necessary for
expression of the COP (Aim 3). Preliminary experiments suggest that dopamine (DA) may play a role in
modulating the effects effects of P1 stimulation. We will confirm and extend these findings, and also investigate
the role(s) of other neuromodulators including biogenic amines such as octopamine (OA), which we have
shown to modulate the effect of P1 stimulation to activate aSP2 neurons that control social behavior9.
Furthermore, we will investigate whether mushroom body (MB) neurons involved in reward learning are also
involved in P1-mediated odor conditioning (Aim 4). Given previous data, we expect to find a role for the MB,
bu...

## Key facts

- **NIH application ID:** 10214916
- **Project number:** 4R37DA031389-11
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** David J Anderson
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $391,704
- **Award type:** 4C
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214916

## Citation

> US National Institutes of Health, RePORTER application 10214916, Imaging neuromodulation in the brain (4R37DA031389-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10214916. Licensed CC0.

---

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