APPARATUS AND SYSTEM FOR TESTING RODENTS' COGNITIVE ABILITY

Abstract

The disclosure relates to an apparatus and a system for testing the cognitive ability of a rodent, comprising a testing chamber, a retarding zone connected to the entrance chamber and including at least one obstacle configured to slow down the rodent's movement to the entrance chamber, and an optional transfer chamber connected to the entrance chamber via the retarding zone for transfer of the rodent to and from an area external to the apparatus. The testing chamber comprises an entrance chamber, a plurality of corridors each connected to the entrance chamber via a corridor's first end portion, and at least one odor diffuser for diffusing odors in the plurality of corridors.

Claims

1. Apparatus for testing the cognitive ability of a rodent, comprising: a testing chamber comprising: an entrance chamber, a plurality of corridors each connected to the entrance chamber via a corridor's first end portion, the plurality of corridors having substantially identical shape and/or dimensions; at least one odor diffuser arranged in at least one of the plurality of corridors, for diffusing odors in the plurality of corridors; and at least one source of reinforcement arranged in the at least one of the plurality of corridors; a retarding zone connected to the entrance chamber and comprising at least one obstacle configured to slow down the rodent's movement to the entrance chamber; and an optional transfer chamber connected to the entrance chamber via the retarding zone for transfer of the rodent to and from an area external to the apparatus.

2. The apparatus of claim 1, wherein the at least one odor diffuser is arranged in a second end portion of the at least one of the plurality of corridors.

3. The apparatus of claim 1, wherein each corridor of the plurality of corridors comprises an odor diffuser and a source of reinforcement.

4. The apparatus of claim 1, wherein the source of reinforcement comprises a source of positive reinforcement and/or a source of negative reinforcement.

5. Apparatus according to claim 1, wherein the apparatus is a module configured to be connected to one or more further modules identical to the module.

6. Apparatus according to claim 1, wherein the plurality of corridors comprises three or more corridors.

7. Apparatus according to claim 1, wherein the area external to the apparatus includes a rest area and/or further apparatuses.

8. Apparatus according to claim 1, wherein the at least one obstacle comprises a floor provided with at least one hole.

9. Apparatus according to claim 1, wherein the retarding zone comprises a retarding chamber, and the at least one obstacle further comprises a platform arranged at an intermediate height of the retarding chamber, adapted to have the rodent's head at the level of the entrance chamber.

10. Apparatus according to claim 1, comprising at least two testing chambers and/or at least two retarding chambers.

11. Apparatus according to claim 10, wherein the at least two testing chambers are of substantially identical shape and dimensions and/or the at least two retarding chambers are of substantially identical shape and dimensions.

12. Apparatus according to claim 1, further comprising a presence sensor arranged in a second end portion of each of the plurality of corridors.

13. Apparatus according to claim 1, wherein the dimensions of each of the plurality of corridors are between 20 and 26 cm in length and between 3 and 7 cm in diameter.

14. System for testing the cognitive ability of a rodent, comprising a plurality of apparatuses according to claim 1 connected to each other by the transfer chamber.

15. Method for testing the cognitive ability of a rodent, comprising: introducing a rodent in the apparatus according to claim 1; diffusing at least one odor in at least one of the plurality of corridors via the at least one odor diffuser; associating the at least one odor with a reward or a reprimand in at least one of the plurality of corridors; triggering the release of the reward or the reprimand when the rodent reaches the second end portion of the at least one of the plurality of corridors where the at least one odor is associated with a reward or, respectively, a reprimand; and assessing a performance of the rodent, wherein the assessing comprises counting the number of times the rodent is successful in getting rewards and/or avoiding reprimands.

16. Method for assessing the efficacy of a drug on a rodent, comprising: applying the method according to claim 15 to the testing of a first rodent; applying the method according to claim 15 to the testing of a second rodent; administering a drug to the second rodent prior to applying the method according to claim 15 to the testing of the second rodent; comparing the performance of the first rodent with the performance of the second rodent; assessing the efficacy of the drug based on the comparison between the performance of the first rodent and the performance of the second rodent.

17. Method according to claim 16, wherein the first rodent and the second rodent are from the same strain.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0064] The present disclosure will be better understood and other advantages and embodiments will become clear on reading the description that follows, given purely by way of indication and in no way limiting, and by referring to the appended figures, in which:

[0065] FIG. 1A is a schematizing representation of an Olfactory Tubing Maze (OTM) according to the prior art.

[0066] FIG. 1B is a schematizing representation of one tube extremity of the OTM of FIG. 1A.

[0067] FIG. 2A is a schematizing representation showing a perspective top view of an example of system for testing the cognitive ability of a rodent according to one or more embodiments of the present disclosure.

[0068] FIG. 2B is an enlarged view of a part of the system shown in FIG. 2A.

[0069] FIG. 2C is an enlarged view of a second end portion of a corridor comprised in the system shown in FIG. 2A.

[0070] FIG. 3 is a schematizing representation of a rodent trying to find its way in the system shown in FIG. 2A.

DETAILED DESCRIPTION OF EMBODIMENTS

[0071] Embodiments of the present disclosure will now be described in detail with reference to the accompanying figures. In the following detailed description of embodiments of the present disclosure, numerous specific details are set forth in order to provide a more thorough understanding of the present disclosure. However, it will be apparent to one of ordinary skill in the art that the present disclosure may be practiced without these specific details. In other instances, well-known features have not been described in detail to avoid unnecessarily complicating the description.

[0072] The following description provides one non-limiting example of a system for testing the cognitive ability of a rodent, according to one or more embodiments of the present disclosure. Such system is depicted in FIG. 2A of the present description. The following description also provides one non-limiting example of use of the system illustrated in FIG. 2A.

[0073] 1. Example of a System for Testing a Rodent's Memory and/or Other Brain Functions

[0074] An example of system 100 for testing the memory and/or other brain functions of a rodent 200 is illustrated in FIG. 2A. The system shown in this figure comprises two identical apparatuses 119 for testing the memory and/or other brain functions of a rodent 200 and a transfer chamber 105 connecting the apparatuses 119 to each other.

[0075] The system 100 may for example be arranged on a table (not shown) of, for example, 110 cm long and 60 cm wide having two square holes (e.g. 60 cm long and 12.5 cm wide) configured to house the apparatuses 119. The table may be mounted on wheels, and may be of sufficient height (e.g. about 1.5 m) to allow some parts of the apparatus, such as transfer chambers identified below, under the table.

[0076] Each apparatus 119 comprises a testing chamber colored in grey and generally designated by reference number 101. Each testing chamber 101 of the system 100 comprises a centrally arranged entrance chamber 102 and a plurality of corridors 104, each connected to the entrance chamber 102 via a first end portion thereof.

[0077] In the embodiment shown in FIG. 2A, the corridors 102 radially extend from the centrally arranged entrance chamber 102 and are angularly equally spaced apart from each other. In the system 100 shown in FIG. 2A, the number of corridors 104 connected to each of the two entrance chambers 102 is four and all corridors 104 connected to a given entrance chamber 102 are spaced apart from each other of an angle 115 of 90°. However, a different number of corridors may be envisaged. In this embodiment, the corridors 104 comprise identical straight tubes of circular cross-section having identical dimensions, e.g. 23 cm in length and 5 cm in diameter. The tubes may be made by joining together two half semicircular tubes one on top of the other. The top half tubes can be easily removed in order to clean the system 100, for example in between two tests.

[0078] The system 100 further comprises odor diffusers 103, which will be described in more details in the following, for diffusing odors in the corridors 102.

[0079] As shown in FIG. 2B, each apparatus 119 further comprises a retarding zone 107 comprising a retarding chamber 107a per each entrance chamber 102. In this example of system 100, each retarding chamber 107a has the form of a cube of side 12 cm. Each retarding chamber 107a is connected to a respective entrance chamber 102 and comprises at least one obstacle 112 configured to slow down the rodent's movement to and from the respective entrance chamber 102. In FIG. 2B, the at least one obstacle 112 comprises a floor 121 fixed at an intermediate height of the retarding chamber 107a and provided with four holes 113. In this example, each hole 113 measures 3.5 cm in diameter. The at least one obstacle 112 further comprises a first platform 114 placed at a predetermined height from the floor 121 of the retarding chamber 107a, adapted to have a rodent's head at the level of the entrance chamber 102, such as illustrated in FIG. 3. In this system 100, the retarding zone 107 further comprises a second platform 118 located below the floor 121 of the retarding chamber 107a for inducing the rodent's movement through the retarding chamber 107.

[0080] In order to make the rodent 200 lose its spatial bearings, equiprobability is respected through certain features of the system 100. For example, the corridors 104 are of substantially identical shape and size. Moreover, the two testing chambers 101 are of substantially identical form and size, and the two retarding chambers 107a are also of substantially identical form and size.

[0081] The system 100 further comprises a transfer chamber, colored in darker grey in both FIGS. 2A and 2B and generally designated by reference number 105, connected to each entrance chamber 102 via the respective retarding chamber 107 to transfer from a first one of the testing chambers 101 to a second one of the testing chambers 101 and vice versa.

[0082] As shown in FIG. 2A, the transfer chamber 105 comprises the retarding chamber 107a of each apparatus 119 and further comprises a transfer tube 106 having end portions each connected to a respective retarding chamber 107a. According to one or more embodiments, the transfer tube 106 comprises an automatic lift door 116 in the middle portion thereof. Such door 116 may be controlled by a control unit (not shown). The door 116 may be set to be closed or open when a rodent is detected in a specific location of the system. For example, the door may be set to be closed when the rodent 200 is detected in a retarding chamber 107a, and/or may be set to be open when the rodent is detected in a second end portion 108 of a corridor 104.

[0083] In each apparatus 119 of the system 100, the odor diffusers 103 are arranged in the second end portions 108 of the each corridor 104. As shown in FIG. 2C, each odor diffuser 103 comprises an air port 103a defined in a wall of each corridor 104, in the second end portion 108 thereof. Each odor diffuser 103 further comprises more pipes 120 connected to the air port 103 for carrying as many odors from respective one or more odor sources or reservoirs (not shown). The diffusion of odors or air in the corridors 104 via the air ports 103 is controlled automatically by means of the control unit, according to a predetermined program. Inverted fans 117 are provided on the top of the entrance chambers 102 to direct neutral or scented air diffused from the second end portions 108 of the corridors 104 from the corridors 104 to the entrance chambers 102 of the testing chambers 101. These inverted fans 117 are also controlled by the control unit.

[0084] As shown in FIG. 2C, the system 100 further comprises a source of positive reinforcement 109 and a source of negative reinforcement 110, both sources 109 and 110 being provided in the second end portion 108 of all corridors 104. Hence, the system 100 shown in FIG. 2A comprises eight sources of positive reinforcement 109, which may be in the form of small water wells having enough volume to contain 500 μL of water, and eight sources of negative reinforcement 110, which may be in the form of means for emitting a non-aversive light signal, such as LED ribbons distributed on an arc extending above the second end portion 108 of all corridors 104 at a height of 18 cm.

[0085] As shown in FIG. 2C, each apparatus 119 further comprises presence sensors 111, including for example photoelectric cells, arranged in each one of the eight second end portions 108 of the eight corridors 104. The photoelectric cells may work in pairs to detect a rodent's movement. For example, one cell may emit an infrared beam that is received by another cell. During a test, an interruption in the infrared beam's reception is caused by the presence of a rodent 200, thus permitting the rodent's detection. In the system 100, the presence sensors 111 are placed 5 cm before each extremity of the corridors 104. The system 100 comprises further photoelectric cells (not shown) at an intermediate height of the retarding chamber 107a for detecting the movement of a rodent in each retarding chamber 107a.

[0086] 2. Example of Use of the System

[0087] To evaluate procedural and declarative-like subcategories of long-term memory, three different strains of mice were submitted in the system 100 described above.

[0088] 2.1. Description of the Experiment

[0089] A first strain of mice was BALB/c Byllco (B) mice because this albinos strain is an excellent learner with olfactory cues (Roman et al.; 2002), but fails to acquire place-learning response in a Morris water maze, which can be explained by an hypersecretion of corticosterone and marked brain catecholamine alterations following stressor exposure.

[0090] A second strain of mice was C57BL/6 mice (C), which is one of the most common strains used to make transgenic or gene-targeting mice.

[0091] A third strain of mice was DBA/2J mice (D) because of some differences in hippocampal anatomy, with their fewer pyramidal cells in the dorsal hippocampus, fewer mossy fiber terminals in the regio inferior, and poor learning performance with spatial or olfactive cues.

[0092] At least 1 week before any training, male adult BALB/c, C57BL/6J and DBA/2J strain mice approximately 8 weeks old were individually housed with free access to food and water in a constant-temperature room (21° C.) maintained on a 12 h light-dark cycle (with lights-on at 07:00 a.m.). Twenty-four mice (eight by strain) were used during three running experiments, corresponding to three mice of the same strain per running experiment.

[0093] Prior to testing them in the running experiments, all mice were subjected first to a procedural training aimed at evaluating the procedural-like subcategories of long-term memory, then to a reference training aimed at evaluating the declarative-like subcategories of long-term memory, which are common to the skilled persona and are thus not detailed here.

[0094] 2.2. Description of the Results

[0095] The percentage of correct responses for each mice strain indicates the effectiveness of the association between the odors and their respective rewards, and is related to declarative memory, while the cumulative time that a rodent spends in the system during an experiment indicates its mastery of the task procedure and is related to non-declarative or procedural memory.

[0096] Taken as a whole, the results demonstrated that the three mice strains were able to learn the long-term-memory procedure requested to get rewards in the system. However, only the B and C mice consolidated the right associations on long-term reference memory, while the D mice started every session of running experiment from the chance level (i.e., 25%).

[0097] The inventors hence showed that the system according to embodiments of the invention provides an experimental frame for sensitive tests that can discriminate mice and effectively and precisely test the different sub-categories of long-term memory.