1. Solicitation Number: NIH-NIDA-NINDS-19-003792

2. Title: Virtual reality systems for mice

3. Classification Code: 66 - Instruments & laboratory equipment

4. NAICS Code: 333999

5. Description: Virtual reality systems for mice

This is a Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice.

This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only.

Background: The National Institute of Neurological Disorders and Stroke (NINDS) is establishing a new laboratory that will use cutting-edge physiological, imaging, and behavioral methods to investigate the relationship between human neurological disorders and brain function at the molecular, synaptic, cellular, and circuit levels. As part of this program, the new laboratory requires two systems for immersing (head-fixed) mice in a virtual reality environment. One of these systems will be used in conjunction with multiphoton microscopy. The other will be used in conjunction with microendoscopic imaging or chronically-implanted extracellular electrodes.

Purpose and Objectives:
The NINDS will soon establish the Laboratory of Circuits, Synapses, and Molecular Signaling (LCSMS), which will be led by the new Scientific Director. The LCSMS will study fundamental issues of synaptic transmission, neuronal excitability, neuromodulation, and neural circuit activity using animal models (principally, the mouse). These issues will be related to human neurological disorders, such as Alzheimer's and other neurodegenerative disorders, and will be explored in brain areas including (but not limited to) the amygdala, basal forebrain cholinergic areas, the ventral hippocampus, and the prefrontal cortex.

A major line of research will employ virtual reality methods to interrogate mouse behavior. These methods will be used in combination with multiphoton microscopy, extracellular electrophysiology, calcium imaging, and/or optogenetics. This research requires two systems that should be tightly integrated with each other: (1) a virtual reality system for head-fixed mice suitable for use with multiphoton microscopy and optogenetics, and (2) a virtual reality system for head-fixed mice suitable for use with extracellular electrophysiology, microendoscopic imaging, and optogenetics.

1. Project requirements: Salient Characteristics

2. The NINDS LCSMS requires two virtual reality systems to interrogate the behavior of head-fixed mice. [In this document, the term "virtual reality" refers to systems that use interactive, computer-generated manipulations of sensory stimuli (visual, tactile, gustatory, olfactory, and/or auditory) to create brain states or provoke behavioral responses mimicking those corresponding to the physical environments being simulated on the computer. Prominent examples of the use of virtual reality in modern neuroscience are described by Harvey et al., Nature 461:941-946 (2009); Agahan et al., Nat. Neurosci. 18:121-128 (2015); Thurley and Ayaz, Curr. Zool. 63:109-119 (2017); and Ravassard et al., Science 340:1342-1346 (2018). The paper by Thurley and Ayaz is a broad review of contemporary efforts.]

I. SYSTEM 1 (multiphoton microscopy and optogenetics)

The first system will be used together with a multiphoton microscope (for example, Scientifica's Hyperscope). It must be compatible with such a microscope in physical arrangement and in how its operations are synchronized (for example, via a TTL signal). The complete microscope system (including virtual reality equipment) will occupy half of a 5' x 10' anti-vibration table. The virtual reality system must also satisfy the following requirements:

• The system must enable the researcher to create a (spatial) virtual reality environment through which the mouse can navigate by moving its limbs while atop a floating ball or a treadmill.

• The horizontal distance between the optical path and the microscope frame will be approximately 8" (depending upon the multiphoton system chosen). The vertical distance between the bottom of the microscope's 40x water-immersion objective and the anti-vibration table upon which the microscope sits will be no more than 10". Any virtual reality equipment underneath the microscope's objective - such as a treadmill or floating ball - must fit in this space.

• The virtual reality system must be suitable for use with a head-fixed mouse. Head fixation will be established by using adjacent posts to secure a metal headplate cemented to the mouse's skull.

• The Contractor must supply a software package for control and programming of the virtual reality environment. The software must allow users to specify the visual reality environment using a graphical user interface, a script, or a high-level programming language. By "high level" we mean a widely-used, interpreted language such as Matlab, LabView, or Python. Compiled languages such as C and C++ are not "high level" by this definition and are not acceptable. The software must allow users to design virtual counterparts of such standard mouse behavioral environments as the T maze, the open field, the Y maze, and the plus maze. The software must also allow coordination with other equipment (such as electrophysiological amplifiers) through the sending and/or receiving of TTL signals.

• A computer capable of running the virtual reality system must be provided, along with all necessary peripherals and cabling. The computer system shall meet or exceed the follow specifications: Windows 10 Pro operating system, Intel Core i7 3GHz processor, 16 GB memory, 256 GB solid-state drive (with at least 1 TB total storage), 19" monitor.

• The head-fixed mouse shall sit atop and move on a floating ball (as, for example, in Harvey et al, Nature 461:941-946 (2009)) or a treadmill (as, for example, in Bittner et al., Nat. Neurosci. 18:1133-1142 (2015)). The system shall include a floating ball, and it must be possible to modify the system to substitute a treadmill. The floating ball shall be air cushioned with a diameter of at least 6". The treadmill shall have ball bearing mounted pulleys.

• In the case of a floating ball, all regulator(s) and other parts necessary for pressure distribution must be provided.

• The principal sensory stimuli manipulated by the virtual reality system will be visual. The system must therefore include visual displays (e.g., a panel of LCD displays) that encompass much of the mouse's visual field. In the horizontal plane, the displays must wrap around by at least 270°; the displays must be at least 19" diagonal.

• The system must be expandable to other sensory modalities. In particular, the system shall include or be able to incorporate a liquid dispenser (liquid reward), a whisker stimulator, a mechanism to deliver an air puff to the mouse's eye, and a system for tone delivery.

II. SYSTEM 2 (microendoscopic, extracellular, optogenetics)

The second system will be used together with microendoscopic imaging (e.g., Inscopix's nVoke), extracellular electrophysiology (e.g., Blackrock Microsystems's CerePlex), and/or optogenetic stimulation (e.g., Doric Lenses light fibers). The virtual reality system must be compatible with these methods and must include some means of synchronizing with them (e.g., by receiving or sending TTL signals.) The system must also satisfy the following requirements:

• The system must enable the researcher to create a (spatial) virtual reality environment through which the mouse can navigate by moving its limbs while atop a floating ball or a treadmill.

• The system will sit on (and must fit on) an anti-vibration table with XY dimensions of 48" x 60".

• The system must be suitable for use with a head-fixed mouse. Head fixation will be established by using adjacent posts to secure a metal headplate cemented to the mouse's skull.

• The Contractor must supply a software package for control and programming of the virtual reality environment. The software must allow users to specify the visual reality environment using a graphical user interface, a script, or a high-level programming language. By "high level" we mean a widely-used, interpreted language such as Matlab, LabView, or Python. Compiled languages such as C and C++ are not "high level" by this definition and are not acceptable. The software must allow users to design virtual counterparts of such standard mouse behavioral environments as the T maze, the open field, the Y maze, and the plus maze. The software must also allow coordination with other equipment (such as electrophysiological amplifiers) through the sending and/or receiving of TTL signals.

• . A computer capable of running the virtual reality system must be provided, along with all necessary peripherals and cabling. The computer system shall meet or exceed the follow specifications: Windows 10 Pro operating system, Intel Core i7 3GHz processor, 16 GB memory, 256 GB solid-state drive (with at least 1 TB total storage), 19" monitor.

• The head-fixed mouse shall sit atop and move on a floating ball (as, for example, in Harvey et al, Nature 461:941-946 (2009)) or a treadmill (as, for example, in Bittner et al., Nat. Neurosci. 18:1133-1142 (2015)). The system must include both a floating ball and a treadmill. The floating ball shall be air cushioned with a diameter of at least 6". The treadmill shall have ball bearing mounted pulleys.

• In the case of a floating ball, all regulator(s) and other parts necessary for pressure distribution must be provided.

• The principal sensory stimuli manipulated by the virtual reality system will be visual. The visual display environment must be dome-shaped with a diameter of more than 1 m and must, in the horizontal plane, encompass at least 200°.

• The system must be expandable to other sensory modalities. In particular, the system shall include or be able to incorporate a liquid dispenser (liquid reward), a whisker stimulator, a mechanism to deliver an air puff to the mouse's eye, and a tone delivery system.

Anticipated period of performance: The contractor shall deliver and install the equipment within 90 days after receipt of order.

Other important considerations: Quantity is two (2). Contractor shall warrant that the Equipment will be free from defects for a period of twelve (12) months from the date of installation, inspection by the Government and acceptance.

Capability statement /information sought. Respondents must provide clear and convincing documentation of their capability of providing the products specified in this notice including providing information regarding being an authorized provider of the services.

The respondent must also provide their DUNS number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HubZone, etc., pursuant to the applicable NAICS code and any other information that may be helpful in developing or finalizing the acquisition requirements.

One (1) copy of the response is required and must be in Microsoft Word or Adobe PDF format using 11-point or 12-point font, 8-1/2" x 11" paper size, with 1" top, bottom, left and right margins, and with single or double spacing.

The information submitted must be in and outline format that addresses each of the elements of the project requirement and in the capability statement /information sought paragraphs stated herein.

The response must include the respondents' technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses.

All responses to this notice must be submitted electronically to the Contract Specialist. Facsimile responses are NOT accepted.

The response must be submitted to Alicia Maldonado Torres, at e-mail address [email protected] .

The response must be received on or before April 8, 2019, 11:00 am, Eastern Time.

Disclaimer and Important Notes: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work.

Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a presolicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation.

Confidentiality: 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)."