Renshaw cells are inhibitory interneurons found in the gray matter of the spinal cord, and are associated in two ways with an alpha motor neuron.
- They receive an excitatory collateral from the alpha neuron's axon as they emerge from the motor root, and are thus "kept informed" of how vigorously that neuron is firing.
- They send an inhibitory axon to synapse with the cell body of the initial alpha neuron and/or an alpha motor neuron of the same motor pool.
| Renshaw cell | |
|---|---|
| Details | |
| Neurotransmitter | Glycine |
| Identifiers | |
| MeSH | D066293 |
| NeuroLex ID | nifext_113 |
| FMA | 86787 |
| Anatomical terms of neuroanatomy | |
In this way, the Renshaw cell action represents a negative feedback mechanism. A Renshaw cell may be supplied by more than one alpha motor neuron collateral and it may synapse on multiple motor neurons.
Function
editAlthough during embryonic development the Renshaw cells lack synapses from the dorsal root, prenatal and postnatal stages show the development of dorsal root originating synapses, which are functional and stimulate action potentials. But these decrease during development while acetylcholine motor axons begin to synapse and proliferate with Renshaw cells, ultimately being primarily stimulated by the motor neurons.[1]
The Renshaw cells are ultimately excited by multiple antidromic motor neuron axons, where the majority of axons originate from synergist motor neurons, and in turn the Renshaw cell synapses with multiple neurons, eliciting IPSP in alpha motor, 1a inhibitory interneurons and gamma motor neurons. The antidromic collateral circuit back to the triggering motor neuron is known as “recurrent inhibition”. This homonymous inhibition is not universal. Whereas most initial experiments have been done on cats, it has been found that in man that proximal muscles of the hand and foot do not have homonymous inhibition. Heteronymous inhibition has been found to be dominant in the leg compared to the arm, where antagonist muscles work simultaneously. (Renshaw cells are activated by gamma motor neurons, but to a lesser extent). The Renshaw cells not only synapse with homonymous and heteronymous nerves, but also with the Ia interneurones, which are stimulated by the Ia afferents from the same muscle group activated by the motor neurons, which have an inhibitory effect on the antagonist muscle group. This “recurrent facilitation” causes reduced inhibition of the reciprocal inhibition of the Ia interneuron of the antagonist group,[2] which may in turn also be inhibited by signals from the corticospinal tract.[3] It has been shown that:[4][5][6]
- Recurrent inhibition is depressed during strong voluntary contractions (presumably due to inhibition of the Reshaw cell by descending input).
- Renshaw cells are more inhibited at the same level during a dynamic contraction compared with sustained contraction.
- Renshaw cells are facilitated during weak voluntary contractions.
- Renshaw cells are facilitated during co-activation of antagonists.
The Renshaw cells may also be inhibited by both proprioceptive dorsal root afferents],[7] antidromic ventral axons[8] as well as “descending” inhibition.[9][10] The hyperpolarization of Renshaw cells by afferent and descending neurons have been shown to be caused by the release of glycine, but GABA may also hyperpolarize the Renshaw cell - for a prolonged time relative to glycine. It has also been shown that glycine is the inhibitory transmitter released by the Renshaw cells.[11][12]
In essence the Renshaw cells regulate the firing of the alpha motor neuron leaving the ventral horn. Conceptually they remove “noise” by dampening the firing frequency of over-excited neurons with a negative feedback loop, which prevents weakly excited alpha motor neurons from firing. Descending spinal cord nerves in turn regulate the Renshaw cells.
The rate of discharge of the Renshaw cell is broadly proportional to the rate of discharge of the associated motor neuron(s), and the rate of discharge of the motor neuron(s) is broadly inversely proportional to the rate of discharge of the Renshaw cell(s). Renshaw cells thus act as "limiters," or "governors," on the alpha motor neuron system, thus helping to prevent muscular damage from tetanus.
Renshaw cells utilize the neurotransmitter glycine as an inhibitory substance that synapses on the alpha motor neurons.
Clinical significance
editRenshaw cells are also the target of the toxin of Clostridium tetani, a Gram positive, spore-forming anaerobic bacterium that lives in the soil, and causes tetanus. When wounds are contaminated with C. tetani, the toxin travels to the spinal cord where it inhibits the release of glycine, an inhibitory neurotransmitter, from Renshaw cells. As a result, alpha motor neurons become hyperactive, and muscles constantly contract.
Strychnine poison also specifically acts on these cell's ability to control alpha motor neuron firing by binding to the glycine receptors on the alpha motor neuron and thus muscles continually contract and may prove fatal if the diaphragm is involved.
History
editThe concept of the Renshaw cells was postulated by Birdsey Renshaw (1911–1948),[13] when it was discovered that with antidromic signals from a motor neuron running collaterally back via the ventral root into the spinal cord, there were interneurons firing with a high frequency, resulting in inhibition. Later work by Eccles et al.,[14] provided evidence that these interneurons, which they called “Renshaw Cells,” are stimulated by acetylcholine from motor neurons (nicotinic receptor). Previous work by Renshaw[15] and Lloyd[16][17] had shown that this antidromic inhibition resembled direct inhibition from spinal nerves but resulted in relatively longer inhibition of 40-50 ms (compared to 15 ms). The antidromic stimulation of the nerve fiber also resulted in action potentials in the cell bodies of the motor neurons along with hyperpolarization of other groups of motor neurons. In the event where the initial stimulation of the motor neuron originated in a spinal tract the Renshaw cell spike occurred during the declining phase of the initial motor neuron soma spike giving an indication of the source and sequence of stimulation of the Renshaw cell.
See also
editReferences
edit- ^ Mentis GZ, Siembab VC, Zerda R, O'Donovan MJ, Alvarez FJ (December 2006). "Primary afferent synapses on developing and adult Renshaw cells". The Journal of Neuroscience. 26 (51): 13297–13310. doi:10.1523/jneurosci.2945-06.2006. PMC 3008340. PMID 17182780.
- ^ Baret M, Katz R, Lamy JC, Pénicaud A, Wargon I (September 2003). "Evidence for recurrent inhibition of reciprocal inhibition from soleus to tibialis anterior in man". Experimental Brain Research. 152 (1): 133–6. doi:10.1007/s00221-003-1547-9. PMID 12898091.
- ^ Mazzocchio R, Rossi A, Rothwell JC (December 1994). "Depression of Renshaw recurrent inhibition by activation of corticospinal fibres in human upper and lower limb". The Journal of Physiology. 481 (Pt 2): 487–498. doi:10.1113/jphysiol.1994.sp020457. PMC 1155947. PMID 7738840.
- ^ Hultborn H, Pierrot-Deseilligny E (December 1979). "Changes in recurrent inhibition during voluntary soleus contractions in man studied by an H-reflex technique". The Journal of Physiology. 297: 229–251. doi:10.1113/jphysiol.1979.sp013037. PMC 1458717. PMID 536912.
- ^ Iles JF, Pardoe J (September 1999). "Changes in transmission in the pathway of heteronymous spinal recurrent inhibition from soleus to quadriceps motor neurons during movement in man". Brain. 122 (Pt 9): 1757–64. doi:10.1093/brain/122.9.1757. PMID 10468514.
- ^ Nielsen J, Pierrot-Deseilligny E (June 1996). "Evidence of facilitation of soleus-coupled Renshaw cells during voluntary co-contraction of antagonistic ankle muscles in man". The Journal of Physiology. 493 (Pt 2): 603–11. doi:10.1113/jphysiol.1996.sp021407. PMC 1158941. PMID 8782120.
- ^ Wilson VJ, Talbot WH, Kato M (November 1964). "Inhibitory convergence upon Renshaw cells". Journal of Neurophysiology. 27 (6): 1063–79. doi:10.1152/jn.1964.27.6.1063. PMID 14223970.
- ^ Ryall RW (March 1970). "Renshaw cell mediated inhibition of Renshaw cells: patterns of excitation and inhibition from impulses in motor axon collaterals". Journal of Neurophysiology. 33 (2): 257–270. doi:10.1152/jn.1970.33.2.257. PMID 4313286.
- ^ Granit R, Haase J, Rutledge LT (December 1960). "Recurrent inhibition in relation to frequency of firing and limitation of discharge rate of extensor motoneurones". The Journal of Physiology. 154 (2): 308–328. doi:10.1113/jphysiol.1960.sp006581. PMC 1359803. PMID 16992068.
- ^ Haase J, van der Meulen J (September 1961). "Effects of supraspinal stimulation on Renshaw cells belonging to extensor motoneurones". Journal of Neurophysiology. 24 (5): 510–520. doi:10.1152/jn.1961.24.5.510. PMID 13710213.
- ^ Curtis DR, Game CJ, Lodge D, McCulloch RM (June 1976). "A pharmacological study of Renshaw cell inhibition". The Journal of Physiology. 258 (1): 227–242. doi:10.1113/jphysiol.1976.sp011416. PMC 1308969. PMID 940060.
- ^ Wilson VJ, Talbot WH (December 1963). "Integration at an Inhibitory Interneurone: Inhibition of Renshaw Cells". Nature. 200 (4913): 1325–1327. Bibcode:1963Natur.200.1325W. doi:10.1038/2001325b0. PMID 14098486.
- ^ Renshaw B (May 1946). "Central effects of centripetal impulses in axons of spinal ventral roots". Journal of Neurophysiology. 9 (3): 191–204. doi:10.1152/jn.1946.9.3.191. PMID 21028162.
- ^ Eccles JC, Fatt P, Koketsu K (December 1954). "Cholinergic and inhibitory synapses in a pathway from motor-axon collaterals to motoneurones". The Journal of Physiology. 126 (3): 524–562. doi:10.1113/jphysiol.1954.sp005226. PMC 1365877. PMID 13222354.
- ^ Renshaw B (March 1941). "Influence of discharge of motoneurons upon excitation of neighboring motoneurons". Journal of Neurophysiology. 4 (2): 167–183. doi:10.1152/jn.1941.4.2.167.
- ^ Lloyd DP (November 1946). "Facilitation and inhibition of spinal motoneurons". Journal of Neurophysiology. 9 (6): 421–438. doi:10.1152/jn.1946.9.6.421. PMID 20274399.
- ^ Lloyd DP (November 1951). "After-currents, after-potentials, excitability, and ventral root electrotonus in spinal motoneurons". The Journal of General Physiology. 35 (2): 289–321. doi:10.1085/jgp.35.2.289. PMC 2147292. PMID 14898019.