Notice Number: NOT-DA-14-028
Release Date: August 18, 2014
Response Date: September 20, 2014
National Institute on Drug Abuse (NIDA)
This is a time-sensitive Request for Information (RFI) directed at obtaining public input to assist the National Institute on Drug Abuse (NIDA) in its planning of an initiative on optimized voltage sensors to measure neuronal membrane potential.
There is currently no effective way to identify and measure how drugs, including drugs of abuse, alter the electrical activity of all the individual neural cells simultaneously in neuronal networks in the nervous system. Accurate, large-scale measurement would allow for the development of improved imaging technologies and improved understanding of the process of addiction and other diseases.
Currently, microelectrodes are able to record the electrical activity of only a few neurons in a neural network consisting of thousands of neurons or just sum the activity of a population of neurons. While current voltage probe, voltage sensitive dyes, or genetically encoded voltage probes provide a direct measure of neuronal activity from thousands of individual neurons at the same time, these technologies lack the spatial and temporal resolution to accurately measure changes in electrical excitability in the nervous system. Accurate measurement of changes in spatial and temporal are needed to measure the summation of the thousands of excitatory and inhibitory inputs to individual neurons that ultimately determine whether a nerve impulse will be fired. Accurate measurement is also needed to count the number of action potentials fired and discern the pattern of action potential firing.
The National Institute on Drug Abuse (NIDA) is considering issuing an initiative on optimized voltage sensors to measure neuronal membrane potential of thousands of individual neurons simultaneously. NIDA is soliciting comments on technical requirements of such sensors and whether these requirements can be achieved within a year.
Speed of response of voltage sensor/probe should be less than or equal to 500 microseconds
Effective detected voltage sensitivity (on typical high end in vivo microscope) for a signal to noise ratio (SNR) of 2 approx. The SNR of 2 should be greater than or equal to 150 microV Hz-2. This implies that changes should be detected of:
10 mV in 1 ms
5 mV in 5 ms
2 mV in 20 ms
The voltage sensor must generate a sufficient number of photons or energy to detect a 100mV change in 1 ms with a signal to ratio of 2 (SNR 2) over shot noise.
Ability to detect a minimum of a 10 mV hyperpolarization in 20 ms of neurons with resting potentials between -40 mV and -90 mV.
Capacitance change <1%.
Ability to detect sensor signal at a depth of at least 1 mm and record continuously for at least 10 minutes without decrement of signal.
Signal from voltage sensor should not decrement.
Soluble or easy to express if genetically encoded.
Targeting specificity - ability to restrict the expression to cell bodies or to dendrites
Ability to detect signal from voltage sensor in thousands of neurons simultaneously.
All responses must be submitted to firstname.lastname@example.org by September 20, 2014.
This RFI is for planning purposes only and should not be construed as a solicitation for applications or an obligation on the part of the government. The government will not pay for the preparation of any information submitted or for the government’s use of that information.
The NIH will use the information submitted in response to this RFI at its discretion and will not provide comments to any responder's submission. However, responses to the RFI may be reflected in future funding opportunity announcements. The information provided will be analyzed and may appear in reports. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information or provide feedback to respondents with respect to any information submitted. No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).
Jonathan D. Pollock, Ph.D.
National Institute on Drug Abuse (NIDA)