Motor Nerve Tracing: Morphology of a Small Motor System
Introduction
If you have not already done so, read Appendix A, Crayfish Neuromuscular Preparation, for background. In Lab 2, Nerve Recording, you used extracellular recording to hypothesize the number of motor neurons innervating the superficial flexor muscle. In this lab, you will test that hypothesis with a staining technique that reveals the number and position of the motor neurons in the central nervous system.
Dissection
In this dissection, you will remove the ventral nerve cord with two adjacent ganglia and both third nerves from the most anterior ganglion. If you are careful, you should be able to obtain at least two such preparations from each crayfish tail.
- Video 3.1, Entire Backfill Procedure, shows the entire dissection. You may want to watch this version during the lab after reading the descriptions below.
- Video A.1, Preparing Crayfish Abdomen. Place a crayfish in the freezer or in ice and leave it until it has stopped moving. Cut off and keep the tail; place the remainder in the freezer. Pin the tail, ventral surface up, in a dissecting dish and cover it with cold crayfish saline.
- Video A.2, Removing Swimmerets. Remove and discard the swimmerets.
- Video 3.2, Exposing Abdominal Ganglia. After using a scalpel to make a slit at the base of each of two adjacent sternites, cut through the sternites with medium scissors. Use a scalpel to remove the thin cuticle over the ventral nerve cord that connects the ganglia. When the ganglia and nerve cord are exposed, use forceps to strip off the blood vessel and connective tissue that are attached to the cord. In this video, the preparation is stained with Janus green dye to make nerves more visible. Do not do this with your preparation.
- Video 3.3, Removing Abdominal Ganglia. Grasp the nerve cord above the rostral ganglion with forceps and cut the cord. Cut all nerves from the two ganglia except for the superficial branch of one or both third nerves. Cut a chunk of superficial flexor muscle attached to nerve 3. Grasp the cut cord above the rostral ganglion, stretch the cord gently, and cut the cord below the caudal ganglion. The two ganglia, with one or two nerves attached to pieces of muscle, should now be free. Place this tissue in a small plastic petri dish and add a droplet of saline.
- Video 3.4, Building Filling Chamber. Use Vaseline to build a two-part chamber in the upside-down lid of a small plastic petri dish. You can do this before the dissection or have your lab partner do it during the dissection.
- Video 3.5, Preparing Ganglia to Fill. Add saline to one side of the Vaseline chamber and place the ganglia in the saline. Grasp the muscle attached to nerve 3 and gently pull the nerve over the central wall into the other side of the chamber. Be careful not to squeeze or stretch nerve 3. Add another layer of Vaseline to the center wall. Using fine scissors, cut nerve 3 between the muscle and the Vaseline wall. Check the chamber for leaks by wicking the saline out of the side with the cut nerve. If saline on the other side is also drawn out, you have a leak that must be fixed before you continue. Replace the saline in the side that contains the cut nerve end with 5% cobalt chloride.
- Cover the preparation with the bottom of the petri dish and place it in the refrigerator. Figure 3.1 shows the preparation in the dish.
- Leave in the refrigerator for 24 to 48 hours. During this time, cobalt diffuses up the axons of the motor neurons.
- After the dissection, rinse all tools with fresh water and lay them aside where they will not be damaged.
Processing
Development
Because the next few steps must be done a day or two after the dissection, your instructor will probably do them. You will continue the procedure at the Evaluation step. Figure 3.2 illustrates processing in flowchart form. You should wear gloves for the procedures described below.
- If it is obvious that cobalt solution has leaked across the Vaseline wall (both sides are pink), it is best to abandon this preparation and start over, because it will stain uniformly black instead of distinguishing the neurons of nerve 3.
- Cut nerve 3 near the ganglion and put the entire nerve cord in a small glass vial of crayfish saline.
- Replace the saline with a 4:1 solution of rubeanic acid and saline and leave it for 5 to 10 min.
- If the preparation turns completely black at this point, stop. Otherwise, continue with the fixation, intensification (optional, see below), and clearing procedures, all of which should be done under a fume hood. Be sure to dump all waste solutions in the waste containers provided under the hood.
Fixation
Wear gloves and do these steps under a fume hood. Dispose of waste solutions in the containers provided under the hood.
- Rinse twice, 3 minutes each, in 70% ethanol.
- Fix for 60 minutes in Carnoy's fixative (6:3:1 mixture of ethanol, chloroform, and glacial acetic acid).
- Rinse and store in 95% ethanol.
It can now be stored in the refrigerator until the next class session.
Evaluation
Look at your preparation under the microscope.
- If dark spots are clearly visible in the ganglia, the stain probably does not need intensification. If so, pin the ganglia in a Sylgard-lined glass petri dish and skip to Tissue Clearing, starting dehydration at the first 100% ethanol step.
- If dark spots are not clearly visible in the ganglia, continue with the Intensification procedure below.
Intensification
Wear gloves and do these steps under a fume hood. Dispose of waste solutions in the containers provided under the hood.
- Rehydrate with a series of rinses of 5 min each in 70% ethanol, then 50% ethanol, then 30% ethanol, then distilled water.
- Place in 2% sodium tungstate solution for 5 min.
- Prepare an intensification solution of 8:1:1 of solutions A, B, and C.
(These three solutions should be freshly prepared by your instructor. Solution A contains water, sodium acetate, acetic acid, silver nitrate, and triton X-100, a surfactant; solution B is sodium tungstate; solution C is ascorbic acid.)
- Place in the intensification solution and leave for 10 to 12 min or until the tissue just begins to turn brown.
- Rinse with several changes of distilled water to stop the reaction.
Clearing
Wear gloves and do these steps under a fume hood. Dispose of waste solutions in the containers provided under the hood.
- Dehydrate the tissue with a series of rinses of 7 min each in 30%, 50%, 70%, and 95% ethanol. At the 50% stage, pin the nerve cord in a Sylgard-lined glass petri dish. Finish the dehydration with two changes of 100% ethanol, 5 min each.
- Put the nerve cord in an equal mixture of 100% ethanol and methyl salicylate for 7 min, followed by pure methyl salicylate (wintergreen oil). This process makes the unstained tissue transparent.
- At this point, the nerve cord may be viewed under the microscope. Place a thin white tissue beneath the slide to diffuse the illumination. This step should also be done under the hood.
- For a more permanent preparation, mount the nerve cord in Permount on a glass depression slide or on a regular slide with staples used to hold the coverslip above the nerve cord.
Further Exploration
Try filling both third nerves in a segment to determine whether the same motor neurons innervate both superficial flexor muscles in that segment or whether the set of motor neurons are duplicated to innervate the other side. To see the position and structure of motor neurons involved in other motor patterns, such as tail flips, swimmeret movements, and tail fan movement, stain the deep branch of nerve 3 (Mittenthal and Wine, 1978), nerve 1, nerve 2, or any of the many nerves that leave the last abdominal ganglion. Nickel can be used instead of or in addition to cobalt in this process (Quicke and Brace, 1978). Try setting up a backfill with one nerve in a pool of cobalt chloride and another nerve in a pool of nickel chloride. You can distinguish the cells filled from the two nerves by their colors (cobalt-filled is red-brown, while nickel-filled is blue-black).
Lab Cleanup
After the dissection is finished and the ganglia are in the filling chamber, put the crayfish tail in the freezer along with the frozen heads, rinse the dissecting dish with fresh water, and clean up any spilled saline or Vaseline. During processing, dispose of chemical wastes in the containers provided in the fume hood.
Questions
- View the nerve cord under the microscope and determine how many motor neurons were stained. How many axons can you see in the nerve? How many cell bodies can you see in the ganglia? Make a sketch of the nerve cord, noting the positions of neuronal cell bodies relative to the midline of the ganglion and any neuronal processes you can see. Where would you expect synaptic input onto the motor neurons (such as input from sensory pathways) to occur?
- If you did Lab 2, Motor Nerve Recording, how does the count of stained cell bodies compare with your estimate of axon number based on the neural recordings? How do you account for any discrepancy? Is the number of cell bodies in the ganglion where nerve 3 originates the same as the number of axons in nerve 3?
- Compare the morphologies of the motor neurons innervating the SF muscle with neuronal morphologies illucidated by various other methods. Consider how morphology facilitates function. For examples, see Lichtman et al. (2008), Mulloney and Hall ( 2000), Murphy (2001), Purali (2005), and Purves et al. (2012).
References
- Kennedy D, Takeda K (1965). Reflex control of abdominal flexor muscles in the crayfish II. The tonic system. J Exp Biol 43:229-246. [pdf]
- Larimer JL, Moore D (2003). Neural basis of a simple behavior: Abdominal positioning in crayfish. Microsc Res Tech 60:346-359. [doi]
- Lichtman JW, Livet J, Sanes JR (2008). A technicolour approach to the connectome. Nat Rev Neurosci 9:417-422. [doi] (For more examples, see cbs.fas.harvard.edu/science/connectome-project/brainbow.)
- Mittenthal JE, Wine JJ (1978). Segmental homology and variation in flexor motoneurons of the crayfish abdomen. J Comp Neurol 177:311-334. [doi]
- Mulloney B, Hall WM (2000). Functional organization of crayfish abdominal ganglia. III. Swimmeret motor neurons. J Comp Neurol 419:233-243. [doi]
- Murphy AD (2001). The neuronal basis of feeding in the snail, Helisoma, with comparisons to selected gastropods. Prog Neurobiol 63:383-408. [doi]
- Purali N (2005). Structure and function relationship in the abdominal stretch receptor organs of the crayfish. J Comp Neurol 488:369-383. [doi]
- Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia A-S, McNamara JO, White LE (2012). Neuroscience (Sinauer Associates, Sunderland MA), ch. 1.
- Quicke DLJ, Brace RC (1979). Differential staining of cobalt- and nickel-filled neurones using rubeanic acid. J Microsc 115:161-163. [doi]
- Silverthorn DU (2013). Human Physiology: An Integrated Approach (Pearson, Boston), ch. 8.
- Wine JJ, Mittenthal JE, Kennedy D (1974). Structure of tonic flexor motoneurons in crayfish abdominal ganglia. J Comp Physiol 93:315-335. [doi]