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Neuromodulatory Control of Circuits Underlying Mental Health Relevant Behaviors
First available due date: February 5, 2025 (link to view opportunity.)
Overview
This Notice of Special Interest (NOSI) solicits applications seeking to understand how neuromodulatory signals dynamically control and coordinate neural circuit responses in real-time during complex mental health relevant behaviors including cognitive, social, and affective functions. These studies are expected to utilize recent tools that enable precise assessment of spatiotemporal dynamics of extracellular release or receptor activation of neuromodulators with simultaneous causal interrogation of neural activity and behavioral responses.
Background and Rationale
Endogenous neuromodulatory systems are implicated in a diverse array of functions and serve as key targets of many existing treatment approaches for mental disorders. While there has been significant prior research trying to study the effects of neuromodulatory systems on specific brain circuits, these studies have typically assessed neuromodulator signaling by using either the activity of neuromodulator-releasing neurons as a proxy for extracellular neuromodulator release, or the modulation of postsynaptic currents. Such an approach is grounded on measurements of action potential activity at the cell body whose output does not fully account for the complex dynamics of downstream neuromodulator release and receptor activation. The ability to directly measure neuromodulator dynamics with high spatiotemporal resolutions has been limited under previously established neurochemical recording techniques. These questions can now be better addressed with recent advances in fluorescent sensors that can be used to simultaneously image multiple different neuromodulator signals with high spatiotemporal resolutions; leveraging molecular and cellular specificity across brain-wide circuits to interrogate specific spatiotemporal dynamics of release in combination with real time measures of complex mental health relevant behaviors.
Specific Areas of Research Interest
Examples of specific research areas of interest include, but are not limited to, the following:
- Temporal dynamics of neuromodulators and neuropeptides and subsequent effects on neural circuit activity and behavior across a range of timescales
- Characterizing the impact and spatiotemporal dynamics of multiple neuromodulators release at the circuit level and their functional role of action on behavior (Applications focusing on co-transmission should target research topics represented in NOT-MH-24-105)
- Coordination of neuromodulator signaling across spatially distributed circuits spanning multiple circuits and/or microcircuits
- Neuromodulatory effects on circuits during early/sensitive periods of development in combination with causal approaches for circuit manipulation to assess relations between aberrant circuit function and maladaptive behavioral trajectories
- Computational models integrating detailed spatiotemporal neuromodulatory signaling with ionotropic neurotransmission and neuronal dynamics (e.g., to make predictions about mechanisms of neuromodulatory impact on network dynamics and behavior)
- Role of neuromodulatory effects on neuron-glia spatiotemporal activity and its relation to cognitive and social-affective behaviors. For example, addressing how neuromodulatory levels, glia activation, and neuronal output coordinate across different spatiotemporal timescales
- Cell-type specificity in both the populations of neuromodulatory cells and their downstream targets within brain-wide circuits underlying mental health-relevant behaviors
Link to funding opportunity.