Abstract:
The disclosed apparatus, systems and methods relate to various devices, systems and methods for gently restraining an unanesthetized laboratory animal, particularly for facial recognition applications. In some applications, the laboratory animal may have been previously cannulated.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims priority to U.S. Provisional Application No. 62/329,712 filed Apr. 29, 2016 and entitled “Animal Collar and Associated Systems and Methods,” which is hereby incorporated by reference in its entirety under 35 U.S.C. §119(e). 
     
    
     GOVERNMENT SUPPORT 
       [0002]    This invention was made with government support under Grant Nos. W81XWH-11-1-0561, W81XWH-16-1-0211 and W81XWH-16-1-0071, each awarded by the Department of Defense (USAMRAA). The government has certain rights in the invention. 
     
    
     TECHNICAL FIELD 
       [0003]    The disclosed technology relates generally to an animal restraint collar and in particular, to the devices, methods, and design principles allowing for the use of restrained use of unanesthetized animals in certain scientific applications. 
       BACKGROUND 
       [0004]    Multiple fields of research use mouse models for pupillometry, facial telemetry, and pain quantification via facial grimace. Current mouse restraint devices that do not require anesthesia fall short in allowing for facial analysis. Additionally, current mouse restraint devices do not allow for cannula injection in unanesthetized mice. 
         [0005]    Thus, there is a need in the art for a better mousetrap: improved devices, systems and methods for restraining unanesthetized animals, including animals already having been cannulated. In exemplary implementations, the various devices, systems and methods here provide a two piece apparatus designed to restrain a mouse in the most minimal manner, without the use of anesthesia, and allow visualization of key facial features and other behavioral analyses. 
       BRIEF SUMMARY 
       [0006]    Discussed herein are various devices, systems and methods relating to an improved collar for use with certain laboratory animals. It is understood that prior art restraint devices that do not require anesthesia fall short in allowing for certain procedures, such as facial analysis. 
         [0007]    One Example includes a collar for restraint of an alert, cannulated laboratory animal, including: a planar base, and a rectangular housing including a first end, a second end and at least one opening, where the housing defines a restraint chamber. 
         [0008]    Implementations of this Example may include one or more of the following features. The collar where the base is substantially planar and includes paired base openings. The collar where the housing further includes mounting brackets defining bracket openings. The collar where the bracket openings are elongate bracket openings. The collar where the housing is configured to be secured to the base via fasteners disposed through the bracket openings into the base openings. The collar where the base and housing are substantially transparent. The collar further including a cannula. The collar where rectangular housing is configured to be in slidable communication with the planar base via the elongate bracket openings. The collar further including a cannula. The collar further including at least one recording device. The collar further including a cannula and at least one recording device. The collar where the planar base and rectangular housing are substantially transparent. The collar where rectangular housing further including mounting brackets defining elongate bracket openings. The collar where the housing is configured to be in slidable communication with the planar base via the elongate bracket openings. The collar further including a cannula. The collar where the base and housing are acrylic. 
         [0009]    Another Example includes a collar system for use with a cannulated laboratory animal, including a planar base including paired base openings and a rectangular housing. The collar system also includes a lumen defining a restraint chamber. The collar system also includes at least one end opening. The collar system also includes paired mounting brackets including elongate bracket openings. The collar system also includes where the rectangular housing is configured to be secured to the base to restrain the animal via fasteners disposed through the elongate bracket openings and paired base openings. 
         [0010]    Implementations of this Example may include one or more of the following features. The collar where rectangular housing is configured to be in slidable communication with the planar base via the elongate bracket openings. The collar further including a cannula. The collar further including at least one recording device. The collar further including a cannula and at least one recording device. The collar where the planar base and rectangular housing are substantially transparent. The collar where rectangular housing further including mounting brackets defining elongate bracket openings. The collar where the housing is configured to be in slidable communication with the planar base via the elongate bracket openings. The collar further including a cannula. The collar where the base and housing are acrylic. 
         [0011]    Another Example includes a collar system for use with a cannulated laboratory animal, including a planar base including paired base openings, a rectangular housing including at least one end opening, the housing defining a restraint chamber, a cannula, and at least one recording device, where the rectangular housing is configured to be secured to the base to restrain the cannulated animal such that the body of the animal is disposed within the housing such that the head of the animal and cannula are disposed outside the housing via the at least one end opening. Implementations of this Example may include one or more of the following features. The collar where rectangular housing further including mounting brackets defining elongate bracket openings. The collar where the housing is configured to be in slidable communication with the planar base via the elongate bracket openings. The collar further including a cannula. The collar where the base and housing are acrylic. 
         [0012]    While multiple embodiments are disclosed, still other embodiments of the disclosure will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the disclosed apparatus, systems and methods. As will be realized, the disclosed apparatus, systems and methods are capable of modifications in various obvious aspects, all without departing from the spirit and scope of the disclosure. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0013]      FIG. 1  is an endlong perspective view of the collar, according to one embodiment. 
           [0014]      FIG. 2  is a three-quarters perspective view of the embodiment of  FIG. 1 . 
           [0015]      FIG. 3A  is an end schematic view of one implementation of the housing. 
           [0016]      FIG. 3B  is a top schematic view of the housing implementation of  FIG. 3A . 
           [0017]      FIG. 3C  is a top schematic view of a base, according to one implementation. 
           [0018]      FIG. 3D  is a endlong perspective view of two implementations of the collar having a housing adopted for use with male mice on the left and a housing adopted for female mice on the right. 
           [0019]      FIG. 4  is a top view of the collar having elongate bracket openings, according to one embodiment. 
           [0020]      FIG. 5A  is a perspective view of one implementation of the collar, wherein the housing has not yet been secured over the animal. 
           [0021]      FIG. 5B  is a perspective view of the collar of  FIG. 5A , wherein the animal has been trapped within the housing. 
           [0022]      FIG. 5C  is a perspective view of the collar of  FIG. 5A , wherein the housing is being oriented atop the base. 
           [0023]      FIG. 6A  is a perspective view of the collar according to one implementation, wherein the user is inserting a first fastener. 
           [0024]      FIG. 6B  is a is a perspective view of the collar of  FIG. 6A , wherein the user is inserting a second fastener. 
           [0025]      FIG. 6C  is a perspective view of the collar of  FIG. 6A , wherein the user is tightening the fasteners to secure the animal. 
           [0026]      FIG. 6D  is a perspective view of a secured animal inside the collar, according to the implementation of  FIG. 6A . 
           [0027]      FIG. 7A  is a perspective side view of the collar system utilizing at least one recording device, according to one implementation. 
           [0028]      FIG. 7B  is a perspective end long rear view of the system of  FIG. 7A . 
           [0029]      FIG. 8A  is a perspective close-up view of the collar system utilizing a cannulated animal, according to one implementation. 
           [0030]      FIG. 8B  is a perspective front view of the implementation of  FIG. 8A . 
           [0031]      FIG. 8C  is a perspective side view of the collar system utilizing a cannulated animal, according to another implementation. 
           [0032]      FIG. 9A  is a perspective close-up view of the collar system, wherein the animal is undergoing eye-blink analysis, according to one implementation. 
           [0033]      FIG. 9B  is another perspective close-up view of the collar system, showing eye blink measurement, according to the implementation of  FIG. 9B . 
           [0034]      FIG. 9C  is a perspective close-up view of the collar system, wherein the animal is undergoing eye-blink analysis during the control condition, according to one implementation. 
           [0035]      FIG. 9D  is another perspective close-up view of the collar system, showing eye blink measurement, according to the implementation of  FIG. 9C . 
       
    
    
     DETAILED DESCRIPTION 
       [0036]    The various embodiments disclosed or contemplated herein relate to an animal restraint  10  or collar  10 . In various implementations, the collar is  10  designed to minimally restrain a laboratory animal—such as a mouse, rat or other lab animal—in the most minimal manner without the use of anesthesia. This has implications for research using animal or mouse models in a variety of fields of scientific study and other applications. 
         [0037]    As one non-limiting example, certain implementations allow for the visualization of key facial features and can be used in various studies, such as pupilometry, facial telemetry, and pain quantification by facial grimace. It is understood that myriad additional implementations are possible, and these would be appreciated by the skilled artisan. 
         [0038]    Turning to the drawings in greater detail, in the implementations of  FIG. 1A-2  the collar  10  has a housing  12  that can be readily attached to a base  14 . In the implementation of  FIGS. 1-2 , the housing  12  is a rectangular, elongate housing  12 . The housing  12  defines an internal lumen  16  that is configured for animal confinement, and is also referred to herein as a restraint chamber  16 . 
         [0039]    The restraint chamber  16  in these implementations has an inner chamber surface  16 A, and the housing has a plurality of chamber walls  18 : a first end wall  18 A and second end wall  18 B, as well as a first side wall  18 C and a second side wall  18 D and an upper wall  18 E, or roof  18 E. In these implementations, the housing walls  18  are substantially planar and of sufficient strength and rigidity to confine the laboratory animal in the restraint chamber  16 . It is understood that in this implementation the housing  12  therefore defines the walls on five of the six sides of the restraint chamber  16 , and the planar base  14  defines the “floor”  20  of the restraint chamber  16 . In use, and as described below, the housing  12  can therefore be used to “catch” and “trap” an alert animal placed on the base  14 . It is understood that in alternate implementations, the housing  12  can have a floor (not shown). 
         [0040]    Continuing with the implementations of  FIGS. 1-2  and  FIGS. 3A-3D , the housing  12  and base  14  can be fabricated from plastic, such as acrylic, or other rigid and durable materials known in the art. In certain implementations, the housing and/or base are transparent or translucent, though it is understood that transparency or translucency is not required for the collar  10  to function in all implementations. 
         [0041]    In the implementations depicted in  FIGS. 1A-3D , a first end opening  22 A and second end opening  22 B allow for the head and tail of the animal (not shown) to extend out of the first end  18  and/or second end  18 B. It is understood that in various implementations, either opening  22 A,  22 B can accommodate the head or tail of the animal, as best shown in  FIGS. 9A-D . 
         [0042]    In the implementation of  FIGS. 3A-3C , various housing  12  dimensions are possible. In certain implementations, and as shown in  FIG. 2 , hashings or markings  30  can be placed on the first end wall  18 A and/or second end wall  18 B to allow for ease in taking measurements of the animal. In certain implementations, numbers or other markings  30  can be used to define increments, such as millimeters. As is also shown in  FIGS. 8A-8B , these markings  30  can be used to measure the animal  1  and its various movements, such as by way of a video camera, as shown for example in  FIGS. 7A-7B  at  50 . 
         [0043]    In an illustrative embodiment of the collar  10 , and as shown in  FIGS. 3A-3D , the dimensions of the chamber  16  were derived from the average dimensions of adult C57BL/6 mice, including skull diameter, neck width, shoulder width, body length, body width, and body height. It is understood that the chamber  16  can be scaled or sized variously for myriad animal types and dimensions. 
         [0044]    Returning to the implementations of  FIGS. 3A-D , in one non-limiting example of a housing  12  according to the implementations of  FIGS. 3A-3D  and configured for a female mouse can be about 23 mm tall (as shown in  FIG. 3A  at reference letter A), while a housing  12  for a male mouse can be about 28 mm tall. Similarly, a housing  12  width (reference letter B) of about 32 mm and opening  22 A width (reference letter C) of about 9.5 mm can be used for non-obese mice, while a housing  12  width of about  41  mm and opening  22 A width of about 11 mm can be used for obese mice. One of skill in the art would appreciate that the housing  12  may be about 65 mm long (reference arrow D), though again, these examples are intended to only be illustrative and can vary from a few millimeters to centimeters, decimeters or meters, depending on the species of animal  1  to be restrained. As shown in FIG. 3 D, in various implementations a male housing  12 A and/or female housing  12 B may be used in conjunction with various bases  14 . 
         [0045]    Continuing with the implementation of  FIGS. 1A-3D , the collar  10  has mounting brackets  24 A,  24 B and fasteners  26 A,  26 B to selectively attach the housing  12  to the planar base  14 , as best shown in relation to  FIGS. 3A-4 . As also best shown in  FIG. 2-3C , the fasteners  26 A,  26 B—such as finger screws or other known bolts or fasteners—can be passed through bracket openings  32 A,  32 B and mounted in base openings  34 A,  34 B, as would be understood by a skilled artisan. 
         [0046]    Turning to the implementation  FIG. 4 , the base  14  has a first paired set of base openings  34 A,  34 B and a second paired set of base openings  34 C,  34 D. Further, in this implementation, the mounting brackets  24 A,  24 B have elongate bracket openings  32 A,  32 B. It is understood that each of these features allow the user to re-position the housing  12  relative to the base  14 , as shown at the reference arrows labeled E. 
         [0047]    For example, in certain implementations the housing  12  can be re-positioned on a coarse level between various mounting positions with the various paired base openings  34 A,  34 B,  34 C,  34 D for use with distinct equipment, as shown generally at  100  in  FIG. 6 ). It is further understood that the use of elongate bracket openings  32 A,  32 B permits the urging of the housing  12  along the base  14 , for example by loosening the fasteners  26 A,  26 B. 
         [0048]    In use, and as shown in the implementations of  FIGS. 5A-6D , an animal  1  such as a mouse  1  can be placed on the base  14 , and the user can bring the housing  12  down over the animal  1 , as shown in  FIG. 5A . It is understood that after the animal  1  has been secured inside the restraint chamber  16 , the housing  12  can be positioned on the base  14 , as is shown in the implementations of  FIGS. 5B-5C . 
         [0049]    As shown in the implementations of  FIGS. 6A-6D , after securing the animal  1  inside the housing  12  restraint chamber  16  and orienting it on the base  14 , the fasteners  26 A,  26 B can be inserted manually through the bracket openings  32 A,  32 B and secured into the applicable base openings  34 A,  34 B,  34 C,  34 D. Other methods of securing the housing  12  to the base  14  are possible, as would be appreciated by one of skill in the art. 
         [0050]    In use, according to certain of the implementations and as also shown in  FIGS. 5A-6D , one of skill in the art would appreciate that precautions can be taken to ensure the paws of the mice or other animals are not pinched while securing the housing  12 . In on illustrative example, such precautions can include securing the housing  12  with only a quarter turn of the fasteners  26 A,  26 B. In certain implementations, this initial securing of the fasteners  26 A,  26 B can be performed while viewing paw placement from the underside of the base  14 , followed by subsequent tightening only after the user has confirmed that all paws and digits are clear. Transparency of the material composing the housing  12  and/or base  14  is thus utilized in certain exemplary implementations. Further, transparent or translucent materials can also provide the user with the ability to monitor the animal&#39;s  1  respiratory rate. 
         [0051]    In certain aspects, the animal  1  such as a mouse must first acclimate to being restrained in the chamber  16 . In various circumstances, because the restraint of the chamber  16  is minimal, certain animals are able to rotate and push against the inner chamber surface  16 A, ends  18 A,  18 B and walls  18 C,  18 D. In certain circumstances, after acclimation, the animal  1  typically resigns to the restraint and normally maintains the natural position. 
         [0052]    In various implementations, the restrained animal  1  can have a range of motion with their head. In certain aspects, this range of motion can be full, except for “tucking.” In various implementations, the restraint chamber provides sufficient space such that the limbs of the animal are able to be freely moved inside the restraint  16 . 
         [0053]    As shown in the implementations of the collar  10  in  FIGS. 7A-7B , the housing  12  and base  14  can be used to restrain or otherwise secure an animal  1  for analysis by way of at least one analytical or recording device  50 , such as a camera  50 . In various implementations, the animal  1  can be positioned such that the animal head  3  is exposed to the device  50 . Further, as would be appreciated by one of skill in the art, in various implementations, certain additional structural components such as scaffolding  52  or the like can be disposed between the housing  12 /base  14  unit and the recording devices  50 . As shown in  FIG. 7B , in certain implementations several recording devices  50 A,  50 B,  50 C,  50 D,  50 E,  50 F can be arrayed around the secured animal  1  so as to record from various angles. 
         [0054]    As shown in  FIGS. 8A-C , in certain implementations of the collar system  10 , the animal  1  may be fitted with a cannula  60  or other implanted device  60  inserted directly into the head  3  of the animal  1 . Critically, in these implementations, the collar  10  is capable of being fitted to the animal  1  after it has been cannulated  60 , as shown above in  FIGS. 5A-6D . 
         [0055]    In various implementations of the collar  10 , therefore, and as shown in FIGS.  FIGS. 8A-C , the collar  10  allows a user to administer various drugs or other substances or stimuli into the brain of an otherwise fully awake or alert animal  1  via the cannula  60 , such as a previously inserted cannula  60 . It is understood that in certain implementations, use of the collar  10  on a previously habituated mouse  1 —or other animal—can allow the user to avoid using anesthesia. It is further appreciated that elimination of anesthesia can present certain methodological advantageous, as anesthesia can confound results. Further, certain aspects can also allow the user to immediately monitor drug responses in the animal without waiting for any effects of anesthesia to subside. 
         [0056]    In certain implementations, the at least one camera  50  can be used for the visualization of key facial features of the animal  1 . In certain non-limiting implementations, the device  10  can allow for the user to record various kinds of data from the animal, such as orbital tightening, nose bulge, cheek bulge, and whisker position, for use in pain assessment, light sensitivity and other kinds of experiments known in the art or as yet developed. It would be understood by one of skill in the art that many additional experiments are possible and contemplated herein. 
         [0057]    For example, in the collar  10  implementations of  FIGS. 9A-9D , the animal  1  can be analyzed for eyeblink conditioning, including the measurement of eye  5  closure (shown in  FIGS. 9A-9B ) compared with normal ( FIGS. 9C-D ), by way of the recording devices  50  (shown in  FIGS. 7A-C ), with or without the application of a certain drug via the cannula. As would be understood by one of skill in the art, many experimental designs are contemplated. 
         [0058]    Although the disclosure has been described with reference to preferred embodiments, persons skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the disclosed apparatus, systems and methods.