Renshaw cells

Acetylcholine is a neurotransmitter at the neuromuscular junction in autonomic ganglia and at postgangHonic parasympathetic nerve endings (see Neuroregulators). In the CNS, the motor-neuron collaterals to the Renshaw cells are cholinergic (43). In the rat brain, acetylcholine occurs in high concentrations in the interpeduncular and caudate nuclei (44). The LD q (subcutaneous) of the chloride in rats is 250 mg/kg. 

Since ACh is the transmitter at the skeletal neuromuscular junction one might also expect it to be released from any axon collaterals arising from the motor nerve to it. Such collaterals innervate (drive) an interneuron (the Renshaw cell) in the ventral horn of the spinal cord, which provides an inhibitory feedback onto the motoneuron. Not... 

Motoneuron-Renshaw cell synapse Nicotinic nicotine Dihydro-B-erythroidine, a-bungarotoxin Excitatory t cation conductance... 

Despite the widespread presence of neuronal nicotinic receptors, for a long time their only known physiological role in the CNS was in mediating the excitation of Renshaw cells by motoneuron axon collaterals (201). The situation has now changed, particularly with respect to the demonstration of a synaptic role, especially for a7-like receptors. 

Receptor Types. In many areas of the CNS, the most represented type of hetero-meric nicotinic receptor is likely to be a4/32 or q 4j82 these receptors correspond to high affinity binding sites for [ H]nicotine. This is likely to be the synaptic receptor on Renshaw cells, which are immunopositiveforthe a4and /32, but not the a 7 subunit, in agreement with the insensitivity of their synaptic responses to methyllycaconitine (202). 

Spinal neurones other than Renshaw cells are not depolarized by acetylcholine . This observation not only underlines the physiological significance of the Renshaw cell sensitivity but it also adds support to the now generally held view that acetylcholine is not the transmitter substance at all synapses in the cord. 

ACETYLCHOLINE In most regions of the CNS, the effects of ACh, assessed either by iontophoresis or by radioligand-binding assays, appear to be generated by interaction with a mixture of nicotinic and muscarinic receptors. Several presumptive chohnergic pathways have been proposed in addition to that of the motoneuron-Renshaw cell. Eight major clusters of ACh neurons and their pathways have been characterized. 

Acetylcholine Approximately 5% of brain neurons have receptors for ACh. Most CNS responses to ACh are mediated by a large family of G protein-coupled muscarinic M receptors that lead to slow excitation when activated. The ionic mechanism of slow excitation involves a decrease in membrane permeability to potassium. Of the nicotinic receptors present in the CNS (they are less common than muscarinic receptors), those on the Renshaw cells activated by motor axon collaterals in the spinal cord are the best-characterized. Drugs affecting the activity of cholinergic systems in the brain include the acetylcholinesterase inhibitors used in Alzheimer s disease (eg, tacrine) and the muscarinic blocking agents used in parkinsonism (eg, benztropine). 

Nicotinic receptors on the Renshaw cell are activated by the release of ACh from motoneuron collaterals. This results in the release of glycine, which, via interaction with its receptors on the motoneuron, causes membrane hyperpolarization—an example of feedback inhibition. The receptors were so-named because of their activation by nicotine. The answer is (D). 

Acetylcholine is the natural transmitter at several different kinds of synaptic site, e.g. (a) the somatic nerve voluntary muscle junctions, (b) the ganglionic synapses which are nerve — nerve junctions in the autonomic system, (c) such postganglionic nerve-endings as are parasympathetic. In addition it has some transmitting duties in the central nervous system, e.g. between spinal cord root fibres and Renshaw cells. 

The only substance reasonably satisfying these conditions is acetylcholine as it affects spinal cord Renshaw cells. At a recent symposium, however, the existence of Renshaw cells as discrete units was challenged on electrophysiological and histochemical grounds but also staunchly defended Little evidence has been presented to support a widespread central transmitter function for acetylcholine. Krnjevi suggested that the slow, prolonged cortical iontophoretic effects of acetylcholine jure consistent with a general facilitatory rather than a direct transmitter action. 

The major site of action is the recurrent inhibitory interneurons (Renshaw cells) of the reflex arc in the spinal cord and medulla. Inhibitory effects in the reflex arc are lost leading to uncontrolled excitation of the spinal reflex. 

The nicotinic effects of ACh are its excitatory action on the autonomic ganglia and the suprarenal glands and its capacity to stimulate the skeletal striated musdes. The nicotinic effects of ACh are reproduced by nicotine and are not abolished by atropine. Nicotinic action on ganglia and suprarenal glands is blocked by hexa-methonium and tetraethylammonium. The nicotinic action of ACh on the skeletal muscles is blocked by tubocurarine. The action of ACh on central nervous system neurons may be of the nicotinic type (for example, Renshaw cells) or of the muscarinic type (certain brain neurons). 

In vertebrates, most of the central neurons are neither cholinergic nor cholino-ceptive. In the spinal cord only the synapses formed by the collaterals of the motoneuron axons on the Renshaw cells have proved to be cholinergic. These synapses are part of the self-inhibitory system of motoneurons. Each impulse being pro-... 

If the endings of the motoneuron axon in skeletal muscles liberate ACh, the collaterals of the same axon forming synapses on the Renshaw cells must release the same transmitter. Indeed, retrograde excitation of the Renshaw cells can be... 

The microapplication of ACh has been shown to induce excitation or inhibition in some brain neurons in the medulla, the midbrain, the mesencephalon, the cerebellum, the caudate nucleus, the cerebral cortex (in the sensory as well as the motor zone), and the cortex of the hippocamp. These effects of ACh can be prevented by cholinolytics. But the microapplication of ACh has revealed some features of brain neurons which are not fully consistent with the hypothesis of the transmitter r61e of ACh. Brain neurons are less sensitive to ACh than the Renshaw cells (where the transmitter role of ACh seems proven beyond a doubt). The response of brain neurons to ACh develops sloniy, after a latency period of several seconds, and lasts a few minutes after the end of microapplication. As the response of the same neurons to the application of exciting amino acids is very quick and short-lasting, the peculiarities of the reaction to ACh cannot be accounted for by the methods employed. 

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