Key Dates

Related Announcements

• May 26, 2022 - Silvio O. Conte Centers for Basic Neuroscience or Translational Mental Health Research (P50 Clinical Trial Optional). See Notice PAR-22-155
• November 16, 2021 - Basic Neurodevelopmental Biology of Circuits and Behavior (R01 Clinical Trial Not Allowed). See Notice PAR-22-066
• November 16, 2021 - Basic Neurodevelopmental Biology of Brain Circuits and Behavior (R21 Clinical Trial Not Allowed). See Notice PAR-22-067
• May 19, 2021 - Academic Research Enhancement Award for Undergraduate-Focused Institutions (R15 Clinical Trial Not Allowed). See Notice PAR-21-155
• March 18, 2021 - Understanding and Modifying Temporal Dynamics of Coordinated Neural Activity (R01 Clinical Trial Optional). See Notice PAR-21-175
• March 18, 2021 - Understanding and Modifying Temporal Dynamics of Coordinated Neural Activity (R21 Clinical Trial Optional). See Notice PAR-21-176
• May 10, 2021- Joint NINDS/NIMH Exploratory Neuroscience Research Grant (R21 Clinical Trial Optional). See Notice PA-21-219
• May 7, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required). See Notice PA-20-196
• May 7, 2020 - NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed). See Notice PA-20-200
• May 5, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Required, Mechanistic Studies Only). See Notice PA-20-183
• May 5, 2020 - NIMH Exploratory/Developmental Research Grant (R21 Clinical Trial Not Allowed). See Notice PA-21-235
• May 5, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See Notice PA-20-185
• May 5, 2020 - NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required). See Notice PA-20-184

Issued by

National Institute of Mental Health (NIMH)

Purpose

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

Applications Not Responsive to this NOSI

• Applications that do not propose concurrent measurements of neuromodulator release and behavior and that do not attempt to assess the impact of neuromodulators on circuits underlying cognition, affect, or social behaviors
• Applications only using in vitro preparations that do not interrogate additional computational or behavioral components of neuromodulation
• Applications assessing the role of neuromodulation on sensory motor function, homeostatic feeding, metabolic, neuroendocrine, thermoregulation, sleep, and circadian behaviors
• Applications proposing to apply animal models of mental disorders or use broad batteries of behavioral tests in animals to address constructs that are accessible only in humans by self-report, such as “depression” or “anxiety,” are not responsive to this NOSI. For additional information on NIMH’s guidelines and priorities for animal neurobehavioral approaches, applicants are strongly encouraged to review NOT-MH-19-053

Application and Submission Information

This notice applies to due dates on or after February 5, 2024 and subsequent receipt dates through May 10, 2027. 

Submit applications for this initiative using one of the following Notice of Funding Opportunity (NOFO) or any reissues of these announcement through the expiration date of this notice.

• PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required, Mechanistic Studies Only)
• PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-20-184 - NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)
• PA-21-235 - NIMH Exploratory/Developmental Research Grant (R21 Clinical Trial Not Allowed)
• PA-20-196 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)
• PA-21-219 - Joint NINDS/NIMH Exploratory Neuroscience Research Grant (R21 Clinical Trial Optional)
• PA-20-200 - NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)
• PAR-21-175 - Understanding and Modifying Temporal Dynamics of Coordinated Neural Activity (R01 Clinical Trial Optional)
• PAR-21-176 - Understanding and Modifying Temporal Dynamics of Coordinated Neural Activity (R21 Clinical Trial Optional)
• PAR-22-066 - Basic Neurodevelopmental Biology of Circuits and Behavior (R01 Clinical Trial Not Allowed)
• PAR-22-067 - Basic Neurodevelopmental Biology of Brain Circuits and Behavior (R21 Clinical Trial Not Allowed)
• PAR-21-155 - Academic Research Enhancement Award for Undergraduate-Focused Institutions (R15 Clinical Trial Not Allowed)
• PAR-22-155 - Silvio O. Conte Centers for Basic Neuroscience or Translational Mental Health Research (P50 Clinical Trial Optional)

All instructions in the SF424 (R&R) Application Guide and the notice of funding opportunity used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-MH-24-100” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed notice of funding opportunity.

Scientific/Research Contact(s)

Siavash Vaziri, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-1576
Email: siavash.vaziri@nih.gov

Fernando Fernandez, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-1576
Email: fernando.fernandez@nih.gov