Hirudo medicinalis

A medicinal leech (photo Annelid Neuroimmunology Laboratory)

Large amount of research has been conducted on the nervous system of the medicinal leech, mainly on behavior, synaptic connections and the function of the ion channels.
These studies have led to a very precise knowledge of the structure of the nervous system, shown in the diagram below. The leech nervous system is composed of a chain of ganglia which are linked to each other by two inter-ganglionic connections composed of nerve fibers. Thus each segment is innervated by one ganglion.
The nerve chain is ventral and enclosed in a blood sinus. The chain begins with four ganglia which innervate the anterior portion of the animal. These ganglia are fused to form two masses. The supra-esophageal ganglia have a role which is limited to neurosecretion whereas the sub-esophageal ganglia have an important sensorial role in innervating the anterior sucker and the three jaws. These two masses are linked to each other, and form a peri-esophageal ring. Next, a segmentary ganglion innervates each segment of the animal’s body. Finally, seven fused ganglia form a voluminous caudal ganglion which principally innervates the posterior sucker of the leech. The nerve chain is covered by a fibrous capsule which contains contractile muscle fibers at the level of the connectives.

Anatomy of the nerve chain of the medicinal leech (orange). (Kuffler, S. W. and Nicholls, J. G. (1976) From Neuron to brain. Sinauer Associates, Inc., Sunderland, Massachusetts).

The neuronal architecture of the segmentary ganglia has been extensively characterized and is extremely well-conserved from one ganglion to another. The ganglia contain about 400 cell bodies each, except for the fifth and sixth ganglia, which are associated with the reproductive system and which have about 700. Within the ganglia, the cell bodies are separated into 6 follicles, enveloped by a glial cell and numerous microglial cells. Because of its structural simplicity, the nervous system is a very accessible tissue, and consequently very useful for in vivo and in vitro experiments.

Hirudo medicinalis’s segmentary ganglia (photo Annelid Neuroimmunology Laboratory)

One of the interesting characteristics of the leech nervous system is its ability to regenerate following a wound or lesion.
When a connective is cut, the swimming movements of the animal are perturbed. Four weeks later, the animal can swim normally, demonstrating that the regeneration is not only structural but also functional (1). Numerous in vivo and in vitro experiments have demonstrated that, unlike mammalian neurons, neurons of the leech have the ability to regenerate sysapses following a lesion, and above all, to regain their functions. Recent findings have demonstrated that microglial cells, as well as components of the extracellular matrix such as laminin, play an important role in axonal growth and the formation of synapses during this regeneration. Lesions of the nervous system also lead to an increase in nitrogen monoxide (NO) and an accumulation of phagocytic microglial cells at the site of the lesion (3,4). These experiments suggest that the production of NO may serve as a signal to inhibit the migration of microglial cells which then accumulate at the site of the lesion. In fact, the increase in NO is due to an activation of a NO synthase which is present in the nervous system after a lesion (5,6). Several experimental observations have indicated an important role for glial cells of the leech in both defense and repair of the nervous system.

In the Annelid Neuroimmunology Laboratory, the research theme devoted to the leech includes four major research axes which are organized chronologically for the study of the response of the central nervous system to an experimental lesion [nb: when I did basic invertebrate biology, we didn’t really consider that the leech had a CENTRALized nervous systen, despite the head ganglia. Maybe this has changed:

1. Alert, protection and signaling. The factors implicated in retrograde transport of information.
   The innate immune response linked to the lesion.
   The signaling molecules which initiate an adaptive response.
2. Repair of the nerve chain.
   Neurotrophic factors in the leech, their receptors and partners.
   Inhibitors of axonal apoptosis.
3. Regeneration of the nerve chain.
   Molecules involved in growth and axonal guidance.
4. Possible biomedical implications in pathologic or accidental lesions of the nervous system.
   In vitro and in vivo testing of the effects of molecules from the leech on Invertebrate and higher Vertebrate models.

References

1. Muller, K. J. and Nicholls, J. G. (1981) Regeneration and Plasticity. In Neurobiology of the leech (Laboratory, C. S. H., ed.), pp. 197-226
2. von Bernhardi, R. and Muller, K. J. (1995) Repair of the central nervous system: lessons from lesions in leeches. J Neurobiol 27, 353-366
3. Chen, A., Kumar, S. M., Sahley, C. L. and Muller, K. J. (2000) Nitric oxide influences injury-induced microglial migration and accumulation in the leech CNS. J Neurosci 20, 1036-1043
4. Kumar, S. M., Porterfield, D. M., Muller, K. J., Smith, P. J. and Sahley, C. L. (2001) Nerve injury induces a rapid efflux of nitric oxide (NO) detected with a novel NO microsensor. J Neurosci 21, 215-220
5. Salzet, M., Salzet-Raveillon, B., Cocquerelle, C., Verger-Bocquet, M., Pryor, S. C., Rialas, C. M., Laurent, V. and Stefano, G. B. (1997) Leech immunocytes contain proopiomelanocortin: nitric oxide mediates hemolymph proopiomelanocortin processing. J Immunol 159, 5400-5411
6. Matias, I., Bisogno, T., Melck, D., Vandenbulcke, F., Verger-Bocquet, M., De Petrocellis, L., Sergheraert, C., Breton, C., Di Marzo, V. and Salzet, M. (2001) Evidence for an endocannabinoid system in the central nervous system of the leech Hirudo medicinalis. Brain Res Mol Brain Res 87, 145-159