The site of anoxic block in the spinal monosynaptic pathway.

Asphyxiation of the spinal cord for periods of 2-4 min leads to block of the monosynaptic pathway. At about the same time this blockage takes place, the afferent action potentials fail to invade the presynaptic terminals. Asphyxiation also interferes with the antidromic invasion of motoneurons, and the failure of the antidromic action potentials to invade the motoneuron dendrites coincides with the time of the disappearance of the orthodromic monosynaptic responses. During reoxygenation, both the presynaptic terminals and the dendrites recover their function, or rather their polarization, in a few seconds and yet synaptic transmission reappears only after several minutes. It is postulated that failure of synaptic transmission during asphyxia is due to depolarization of both the presynaptic terminals and the dendrites of the postsynaptic elements. However, repolarization of these elements during reoxygenation, is not sufficient to reestablish synaptic transmission, but recovery of some unidentified biochemical process is apparently necessary.     

Early and late post-tetanic potentiation,and post-tetanic block in a monosynaptic reflex pathway

Observations have been made upon the nature of early and late post-tetanic potentiation and upon post-tetanic block of presynaptic collaterals with particular reference to behavior in circumstances of varied duration and frequency of conditioning stimulation. Early potentiation is most conspicuous following brief tetani at high frequency, late potentiation following long tetani, much lower frequencies being all that are needed. The two phenomena thus are distinguishable and separate. Dorsal root electrotonus produced by stimulations of varying duration and frequency is described, and the similarity between behavior of the D.R.IV R. electronic potential and early potentiation demonstrated. It is shown how early potentiation and post-tetanic block are due to the same process (hyperpolarization) at different intensities. The view that the agency for potentiation is associated with augmented presynaptic action due to hyperpolarization is confirmed. A diagram is constructed to indicate the probable temporal courses of early and late potentiation.     

Involvement of NO-guanylyl cyclase pathway for the depression of spinal monosynaptic reflex by Mesobuthus tamulus venom in neonatal rat in vitro

AimsThe present study was undertaken to evaluate the role of nitric oxide (NO) in Mesobuthus tamulus (MBT) venom-induced depression of spinal reflexes.Main methodsExperiments were performed on isolated hemisected spinal cords from 4 to 6 day old rats. Stimulation of a dorsal root with supramaximal strength evoked monosynaptic (MSR) and polysynaptic reflex (PSR) potentials in the corresponding segmental ventral root.Key findingsSuperfusion of MBT venom (0.3 μg/ml) depressed the spinal reflexes in a time-dependent manner and the maximum depression was seen at 10 min (MSR by 63%; PSR by 79%). The time to produce 50% depression (T-50) of MSR and PSR was 7.7 ± 1.3 and 5.7 ± 0.5 min, respectively. Pretreatment with bicuculline (1 μM; GABA_A receptor antagonist) or strychnine (1 μM; glycine_A receptor antagonist) did not block the venom-induced depression of spinal reflexes. However, Nω-nitro-L-arginine methyl ester (L-NAME, 100 or 300 μM; NO synthase inhibitor) or hemoglobin (Hb, 100 μM; NO scavenger) antagonized the venom-induced depression of MSR. Further, soluble guanylyl cylase inhibitors (1 H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one, ODQ; 1 μM or methylene blue, 100 μM) also antagonized the venom-induced depression of MSR but not PSR. Nitrite concentration (indicator of NO activity) of the cords exposed to venom (0.3 μg/ml) was not different from the control group.SignificanceThe results indicate that venom-induced depression of MSR is mediated via NO-guanylyl cyclase pathway without involving GABAergic or glycinergic system.     

Suppression of abnormally increased excitability of monosynaptic spinal reflex arcs by riluzole

We studied the effects of a neuroprotector, riluzole, on the evoked mass activity of spinal neuronal mechanisms and on action potentials (APs) recorded from the sciatic nerve in intact rats and rats with the manifestations of postdenervational and 4-aminopyridine (4-AP)-induced hyperreflexia, as well as in animals in the superreflexia state (induced by combined action of denervation and 4-AP). We measured the parameters of monosynaptic reflex discharges (monosynaptic reflexes, MRs) recorded from the ventral root (VR), of the spinal dorsal surface potential (DSPs), and of mass APs evoked in afferent and efferent fibers of the SN before and 10, 30, 60, and 120 min after injection of riluzole. It was found that in intact animals riluzole significantly (by 60–70%) decreased the amplitude of VR MRs and those of the afferent peak and N₁ component of DSPs. Riluzole exerted smaller suppressive effects on mass APs in the afferent fibers of the SN; the effect on APs in the SN efferent fibers was the minimum (a 4 to 5% decrease). Under conditions of increased sensitivity of the motoneuronal postsynaptic membrane to the transmitter (postdenervational hyperreflexia) and an increased release of glutamate from presynaptic elements (4-AP-induced hyperreflexia), as well as under superreflexia conditions, the dynamics of suppression of the evoked spinal activity by riluzole showed relatively moderate differences from those in intact animals. Under the above conditions, riluzole in the same manner decreased the amplitude of VR MRs. In the superreflexia state, the agent blocked the development of additional components of these dramatically increased potentials (in the above state, their amplitude increased by nearly nine times, on average, and this resulted in the generation of such components). We believe that the inhibitory effect of riluzole on glutamatergic neurotransmission in the spinal cord is based, first of all, on blocking of excitation in afferent presynaptic terminals. The possibility to use riluzole for correction of abnormally increased hyperexcitability of the spinal neuronal systems is discussed. Neirofiziologiya/Neurophysiology, Vol. 37, Nos. 5/6, pp. 416–423, September–December, 2005.     

The role of mTOR signaling pathway in spinal cord injury

The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in multiple cellular functions, such as cell metabolism, proliferation and survival. Many previous studies have shown that mTOR regulates both neuroprotective and neuroregenerative functions in trauma and various diseases in the central nervous system (CNS). Recently, we reported that inhibition of mTOR using rapamycin reduces neural tissue damage and locomotor impairment after spinal cord injury (SCI) in mice. Our results demonstrated that the administration of rapamycin at four hours after injury significantly increases the activity of autophagy and reduces neuronal loss and cell death in the injured spinal cord. Furthermore, rapamycin-treated mice show significantly better locomotor function in the hindlimbs following SCI than vehicle-treated mice. These findings indicate that the inhibition of mTOR signaling using rapamycin during the acute phase of SCI produces neuroprotective effects and reduces secondary damage at lesion sites. However, the role of mTOR signaling in injured spinal cords has not yet been fully elucidated. Various functions are regulated by mTOR signaling in the CNS, and multiple pathophysiological processes occur following SCI. Here, we discuss several unresolved issues and review the evidence from related articles regarding the role and mechanisms of the mTOR signaling pathway in neuroprotection and neuroregeneration after SCI.     

The role of mTOR signaling pathway in spinal cord injury

The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in multiple cellular functions, such as cell metabolism, proliferation and survival. Many previous studies have shown that mTOR regulates both neuroprotective and neuroregenerative functions in trauma and various diseases in the central nervous system (CNS). Recently, we reported that inhibition of mTOR using rapamycin reduces neural tissue damage and locomotor impairment after spinal cord injury (SCI) in mice. Our results demonstrated that the administration of rapamycin at four hours after injury significantly increases the activity of autophagy and reduces neuronal loss and cell death in the injured spinal cord. Furthermore, rapamycin-treated mice show significantly better locomotor function in the hindlimbs following SCI than vehicle-treated mice. These findings indicate that the inhibition of mTOR signaling using rapamycin during the acute phase of SCI produces neuroprotective effects and reduces secondary damage at lesion sites. However, the role of mTOR signaling in injured spinal cords has not yet been fully elucidated. Various functions are regulated by mTOR signaling in the CNS, and multiple pathophysiological processes occur following SCI. Here, we discuss several unresolved issues and review the evidence from related articles regarding the role and mechanisms of the mTOR signaling pathway in neuroprotection and neuroregeneration after SCI.     

The monosynaptic connection between identified neurons in the snail

Monosynaptic connection between two identified neurones was investigated using electrophysiological and morphological methods in preparation of isolated nervous system of the snail Achatina fulica. Intracellular pressure injection of cobalt chloride was used for staining of neuronal branches. Electrophysiologically revealed synaptic connection between two giant neurones was identified to be monosynaptic by morphological methods.     

大鼠坐骨神经挤压损伤导致脊髓单突触反射回返性抑制的长时程减弱

坐骨神经损伤是临床常见的周围神经疾病。神经损伤后再生肌肉和运动神经元会出现各种功能障碍,虽然其中一部分因素已被阐明,但多局限于受损神经局部,而对于再生后脊髓运动神经元的回返性抑制(recurrent inhibition,RI)通路的功能变化却很少被报道。本文研究大鼠短暂坐骨神经损伤后,恢复神经再支配(reinnervation)情况下,脊髓RI通路的功能变化。在正常或坐骨神经挤压(crush)受损后的成年大鼠上,通过刺激离断的脊髓背根(L5),在外侧腓肠肌-比目鱼肌(lateral gas-trocnemius-soleus,LG-S)神经或内侧腓肠肌(medial gastrocnemius,MG)神经记录单突触反射(monosynaptic reflex,MSR),并同时在另一神经给予条件性刺激,以检测LG-S和MG运动神经元间RI的变化。结果显示:(1)脊髓运动神经元的RI在坐骨神经挤压受损后即基本丢失(<5周),至损伤6周后部分恢复至正常的50%,并至少维持至损伤14周后;(2)一侧的坐骨神经损伤对对侧的RI没有影响;(3)外周神经损伤后,免疫组织化学方法显示脊髓运动神经元数目本身并不发生减少。以上...     

Influence of different barbiturate anesthetics on delta-9-tetrahydrocannabinol effects on spinal monosynaptic reflexes

Two barbiturates, pentobarbital and methohexital, were used as general anesthetics to evaluate their interactions with the effects of delta-9-tetrahydrocannabinol (delta-9-THC) on spinal monosynaptic reflexes in cats with transected spinal cords and ischemically destroyed brains. In animals initially anesthetized with pentobarbital, delta-9-THC over a wide dosage range produced only an enhancement of the reflex, whereas in methohexital-treated animals only depression was elicited. Because delta-9-THC is known to produce both excitatory and depressant effects in conscious animals, the results of the present study demonstrate that the choice of anesthetic may determine which effects manifest themselves. Therefore, if anesthesia is used in the investigation of any cannabinoid, the possibility of such interactions must be considered when interpreting the results.