Polysynaptic

Normal function Transduction Conduction Processing, mono- and polysynaptic-re-flexes Processing, perception, emotional components of pain, polysynaptic reflexes... 

Several classes of drugs modulate the firing rates or patterns of midbrain dopamine neurons by direct, monosynaptic, or indirect, polysynaptic, inputs to the cell bodies within the ventral mesencephalon (i.e., nicotine and opiates). In contrast, amphetamine, cocaine, and methylphenidate act at the level of the dopamine terminal interfering with normal processes of transmitter packaging, release, reuptake, and metabolism. 

The cells comprising lamina V are more diverse than those of lamina IV and their dendrites extend vertically toward the superficial layers. Cell bodies in lamina V contribute to three projection pathways, the SCT, PSDC and STT. However, the STT cells appear to be predominant in this lamina. Lamina V plays an important role in nociception since it receives both A - and C-fibre inputs. Some cells in lamina V also respond to cutaneous low- and high-threshold mechanical stimuli and receive nociceptive inputs from the viscerae. Many of these neurons also project onto mononeurons and so act as interneurons in the polysynaptic withdrawal reflex to noxious stimuli. 

Figure 7.3 Components of a reflex arc. As illustrated by the components of the reflex arc, reflexes may be processed entirely at the level of the spinal cord with no need for input from the brain. A monosynaptic reflex has a single synapse between afferent and efferent neurons a polysynaptic reflex has two or more synapses between these neurons. In this case, intemeurons lie between the sensory and motor neurons. The more intemeurons involved, the more complex the response is.

A reflex is initiated by stimulation of a sensory receptor located at the peripheral ending of an afferent or first-order sensory neuron. This afferent neuron transmits impulses to the spinal cord. Within the gray matter of the spinal cord, the afferent neuron synapses with other neurons. As such, the spinal cord serves as an integrating center for the sensory input. The afferent neuron must ultimately synapse with an efferent or motor neuron. When the afferent neuron synapses directly with the motor neuron, it forms a monosynaptic reflex. An example of this type of reflex is the stretch reflex. When the afferent neuron synapses with an intemeuron that then synapses with the motor neuron, it forms a polysynaptic reflex, e.g., the withdrawal reflex. Most reflexes are polysynaptic. The motor neuron then exits the spinal cord to innervate an effector tissue, which carries out the reflex response. 

An interneuron together with a sensory afferent and motor efferent form a polysynaptic reflex (Figure 2.2) this comprises the initial stage of information input (sensory afferent), the processing/computing an appropriate response (interneurons) and the execution of a behavioural response (motor efferent). The simplest reflexes in the nervous system are monosynaptic reflexes, such as the familiar tendon (knee) jerk, these do not involve an interneuron. The sensory afferent activated by the mechano-receptor (the tap of the patellar hammer) forms a synapse with the motor efferent in the spinal cord, which then causes the skeletal muscle to contract and the crossed leg to jerk forward. With a synaptic delay of 1 millisecond (ms), the time between input and output increases with the number of synapses introduced into the circuit. As an... 

Due to its relevance to an understanding of movement disorders, the motor circuit has received the most attention. This circuit is centered on somatosensory, motor and premotor cortices, which send projections to the motor portions of striatum. The connections between the striatum and the basal ganglia output nuclei (GPi/SNr) are organized into direct and indirect pathways [1]. The direct pathway is a monosynaptic projection between striatum and GPi/ SNr, while the indirect pathway is a polysynaptic connection that involves intercalated neurons in GPe and STN. Some striatofugal neurons may also collateralize more extensively, reaching GPe, GPi/SNr and STN. Other motor -related inputs to striatum and STN arise from the intralaminar thalamic nuclei, i.e. the centromedian and parafascicular nuclei (CM/Pf). 

Recent data utilizing a polysynaptic withdrawal reflex suggest that, in intact rats, a disinhibition hypothesis may be necessary to explain some of the facilitatory effects of hallucinogens. Low to moderate doses of the hallucinogen 5-MeODMT administered into the lateral ventricle facilitated (i.e., decreased the latency of) the tail flick response to radiant stimulation of the tail (22). Furthermore, either spinal transection alone or systemic administration of 5-HT antagonists in intact... 

Direct evidence is also available from functional studies that LSD can act as a serotonin antagonist. Anderson (9) has reviewed experiments on spinal reflexes conducted in acute spinal cats in which stimulation of the dorsal roots elicits monosynaptic, polysynaptic, and dorsal root reflexes. Increases in CNS levels of serotonin increased the size of the monosynaptic reflex and decreased the size of the polysynaptic and dorsal root reflexes. The increase in magnitude of the monosynaptic reflex induced by serotonin was blocked by a variety of classic serotonin antagonist drugs in addition, it was blocked by the systemic administration of LSD. Decreases in the other two types of spinal reflexes were unaffected by LSD and the serotonin antagonists. 

Further investigations on the site of action of clonidine in the spinal cord have been performed by AN-DfiN and coworkers (19). Injection of dopa caused in rats an intensified polysynaptic flexor reflex of the... 

Pharmacology The precise mechanism of action is not known. Baclofen can inhibit mono- and polysynaptic reflexes at the spinal level, possibly by hyperpolarization of afferent terminals, although actions at supraspinal sites also may contribute to its clinical effect. Baclofen has CNS-depressant properties. 

Baclofen appears to affect the neuromuscular axis by acting directly on sensory afferents, y-motor neurons, and collateral neurons in the spinal cord to inhibit both monosynaptic and polysynaptic reflexes. The principal effect is to reduce the release of excitatory neurotransmitters by activation of presynaptic GABAg receptors. This seems to involve a G protein and second-messenger link that either increases K+ conductance or decreases Ca conductance. 

Benzodiazepines also possess muscle relaxant activity. Their pharmacology is discussed in Chapter 30. Diazepam Valium) has been used for control of flexor and extensor spasms, spinal spasticity, and multiple sclerosis. The muscle relaxant effect of the benzodiazepines may be mediated by an action on the primary afferents in the spinal cord, resulting in an increased level of presynaptic inhibition of muscle tone. Polysynaptic reflexes are inhibited. The most troublesome side effect is drowsiness, which is dose dependent. Tolerance to both the therapeutic effects and the side effects develops. 

Benzodiazepines have the capacity to depress polysynaptic reflexes and have been shown to decrease decerebrate rigidity in cats and spasticity in patients with cerebral palsy. What is not clear is whether they can, in humans, relax voluntary muscles in doses that do not cause considerable central nervous system depression. Nevertheless, benzodiazepines, such as diazepam, are often prescribed for patients who have muscle spasms and pain as a result of injury. In these circumstances, the sedative and anxiolytic properties of the drug also may promote relaxation and relieve tension associated with the condition. 

Mechanism of Action A barbiturate that increases seizure threshold in the motor cortex. Therapeutic Effect Depresses monosynaptic and polysynaptic transmission in... 

It causes skeletal muscle relaxation by preferential blockade of polysynaptic spinal reflexes. 

Tizanidine is an a -adrenergic receptor agonist at supraspinal and spinal levels. This effect results in inhibition of spinal polysynaptic reflex activity. It presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. Tizanidine has no direct effect on skeletal muscle, the neuromuscular junction or on monosynaptic reflex activity. 

It is beta-4 (chlorophenyl)-gamma aminobutyric acid. It is a powerful neuronal depressant. It reduces the release of excitatory transmitter and is antinociceptive in animal studies. It inhibits monosynaptic and polysynaptic reflex transmission at spinal level, probably by stimulating the GABAg... 

Some sedative-hypnotics, particularly members of the carbamate (eg, meprobamate) and benzodiazepine groups, exert inhibitory effects on polysynaptic reflexes and internuncial transmission and at high doses may also depress transmission at the skeletal neuromuscular junction. Somewhat selective actions of this type that lead to muscle relaxation can be readily demonstrated in animals and have led to claims of usefulness for relaxing contracted voluntary muscle in muscle spasm (see Clinical Pharmacology). Muscle relaxation is not a characteristic action of zolpidem, zaleplon, and eszopiclone. 

It is not clear, however, exactly how these drugs inhibit neurons involved in the polysynaptic pathways. There is preliminary evidence that one of these compounds (cyclobenzaprine) might block serotonin receptors on spinal interneurons, thereby decreasing the excitatory influence of serotonin on alpha motor neuron activity.50,55 Although this effect has been attributed to cyclobenzaprine in animals (rats), the effect of this drug and other muscle relaxants in humans remains to be determined. 

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