Stimulation of dorsal root afferents increases the excitability of ascending sensory axons in the isolated spinal cord of mature mice

2010 ◽  
Vol 1356 ◽  
pp. 24-31
Author(s):  
Md Harunor Rashid ◽  
Jose A. Lopez-Garcia ◽  
Fernando Cervero
1993 ◽  
Vol 70 (3) ◽  
pp. 1151-1158 ◽  
Author(s):  
M. Pinco ◽  
A. Lev-Tov

1. The effects of high-frequency (5-50 Hz) stimulation of dorsal root afferents on monosynaptic excitation of alpha motoneurons was studied in the in vitro spinal cord preparation of the neonatal rat, using sharp-electrode intracellular recordings. 2. Double pulse stimulation of dorsal root afferents induced severe depression of testing excitatory postsynaptic potentials (EPSPs) at each of the tested interstimulus intervals (15 ms-5 s). After perfusion of the preparation with low-calcium, high-magnesium Krebs saline, the amplitude of the conditioning EPSPs was markedly decreased and the testing EPSPs exhibited substantial facilitation that was maximal at the 20-ms interval and that was accompanied by depression at intervals > or = 60-100 ms. 3. Short-duration stimulus trains applied to dorsal root afferents normally induced tetanic depression of the intracellularly recorded monosynaptic EPSPs. Switching the bathing solution to low-calcium, high-magnesium saline decreased the control EPSP and induced facilitation and then tetanic potentiation (TP) of the EPSPs within the applied train. The magnitude of potentiation (% potentiation) of these EPSPs depended on the interpulse interval of the short stimulus train and on the degree of attenuation of the unpotentiated control EPSP after the solution was changed from normal- to low-calcium Krebs solution. 4. Long-duration stimulus trains applied to dorsal root afferents at 5-10 Hz induced marked depression of monosynaptic EPSPs during the train. The depression was alleviated after cessation of the tetanic stimulation and was followed in some cases by slight posttetanic potentiation.(ABSTRACT TRUNCATED AT 250 WORDS)


1993 ◽  
Vol 70 (1) ◽  
pp. 406-417 ◽  
Author(s):  
M. Pinco ◽  
A. Lev-Tov

1. Excitatory synaptic transmission in mono- and polysynaptic pathways between dorsal root afferents and alpha-motoneurons was studied in the spinal cord preparation of the neonatal rat isolated in vitro, using sharp-electrode intracellular recordings. 2. The duration of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited in lumbar motoneurons were shortened after addition of the specific N-methyl-D-aspartate (NMDA) receptor blocker 2-amino-5-phosphonovaleric acid (APV) to the perfusate. The EPSPs were then completely blocked by the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 3. A robust NMDA-receptor-mediated component of monosynaptic EPSPs was revealed by addition of CNQX to the bathing medium. This component reached as much as 30% of the EPSP amplitude, was evident at resting potential level in both low and normal Mg2+ Krebs saline, and could be completely abolished by addition of APV. These findings suggest that the NMDA-receptor-mediated component may contribute to monosynaptic excitation under normal conditions. 4. Polysynaptic EPSPs evoked in motoneurons in the fifth lumbar segment by stimulation of the fourth lumbar dorsal root in the presence of the glycine and gamma-aminobutyric acid A (GABAA) receptor blockers strychnine and bicuculline could be completely or partially blocked by application of either APV or CNQX. Suprathreshold activity could be then elicited in these motoneurons by increasing the stimulation intensity by a factor of 2 to 3. A complete blockade of polysynaptic excitation at these stimulation intensities was obtained only in the presence of both APV and CNQX. These results suggest that both receptor subtypes make a significant contribution to polysynaptic excitation of alpha-motoneurons by dorsal root afferents. 5. Analysis of variation in the amplitudes of the non-NMDA-receptor-mediated component of the monosynaptic EPSP and of the estimated (occurring 25 ms after the EPSP initiation) and the pharmacologically resolved NMDA component was done during low-frequency repetitive stimulation of the dorsal root. The kinetics of the initial decrease in EPSP amplitude during repetitive stimulation and the dependence of the EPSP amplitude on the stimulation frequency was similar for the NMDA- and non-NMDA-receptor-mediated components of the EPSPs. Addition of the GABAB receptor agonist L-(-) baclofen to the perfusate decreased the EPSP amplitude and reduced the frequency-dependent synaptic depression of both the NMDA- and non-NMDA-receptor-mediated components of monosynaptic EPSPs to the same level.(ABSTRACT TRUNCATED AT 400 WORDS)


1998 ◽  
Vol 79 (5) ◽  
pp. 2581-2592 ◽  
Author(s):  
E. Kremer ◽  
A. Lev-Tov

Kremer, E. and A. Lev-Tov. GABA-receptor–independent dorsal root afferents depolarization in the neonatal rat spinal cord. J. Neurophysiol. 79: 2581–2592, 1998. Dorsal root afferent depolarization and antidromic firing were studied in isolated spinal cords of neonatal rats. Spontaneous firing accompanied by occasional bursts could be recorded from most dorsal roots in the majority of the cords. The afferent bursts were enhanced after elevation of the extracellular potassium concentration ([K+]e) by 1–2 mM. More substantial afferent bursts were produced when the cords were isolated with intact brain stems. Rhythmic afferent bursts could be recorded from dorsal roots in some of the cords during motor rhythm induced by bath-applied serotonin and N-methyl-d-aspartate (NMDA). Bilaterally synchronous afferent bursts were produced in pairs of dorsal roots after replacing the NaCl in the perfusate with sodium-2-hydroxyethansulfonate or after application of the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline with or without serotonin (5-HT) and NMDA. Antidromic afferent bursts also could be elicited under these conditions by stimulation of adjacent dorsal roots, ventrolateral funiculus axons, or ventral white commissural (VWC) fibers. The antidromic bursts were superimposed on prolonged dorsal root potentials (DRPs) and accompanied by a prolonged increase in intraspinal afferent excitability. Surgical manipulations of the cord revealed that afferent firing in the presence of bicuculline persisted in the hemicords after hemisection and still was observed after removal of their ventral horns. Cutting the VWC throughout its length did not perturb the bilateral synchronicity of the discharge. These findings suggest that the activity of dorsal horn neurons is sufficient to produce the discharge and that the bilateral synchronicity can be maintained by cross connectivity that is relayed from side to side dorsal to the VWC. Antagonists of GABAB, 5-HT2/5-HT1C, or glutamate metabotropic group II and III receptors could not abolish afferent depolarization in the presence of bicuculline. Depolarization comparable in amplitude to DRPs, could be produced in tetrodotoxin-treated cords by elevation of [K+]e to the levels reported to develop in the neonatal rat spinal cord in response to dorsal root stimulation. A mechanism involving potassium transients produced by neuronal activity therefore is suggested to be the major cause of the GABA-independent afferent depolarization reported in our study. Possible implications of potassium transients in the developing and the adult mammalian spinal cord are discussed.


2013 ◽  
Vol 109 (8) ◽  
pp. 2118-2128 ◽  
Author(s):  
Patrick M. Sonner ◽  
David R. Ladle

Sensory feedback is critical for normal locomotion and adaptation to external perturbations during movement. Feedback provided by group Ia afferents influences motor output both directly through monosynaptic connections and indirectly through spinal interneuronal circuits. For example, the circuit responsible for reciprocal inhibition, which acts to prevent co-contraction of antagonist flexor and extensor muscles, is driven by Ia afferent feedback. Additionally, circuits mediating presynaptic inhibition can limit Ia afferent synaptic transmission onto central neuronal targets in a task-specific manner. These circuits can also be activated by stimulation of proprioceptive afferents. Rodent locomotion rapidly matures during postnatal development; therefore, we assayed the functional status of reciprocal and presynaptic inhibitory circuits of mice at birth and compared responses with observations made after 1 wk of postnatal development. Using extracellular physiological techniques from isolated and hemisected spinal cord preparations, we demonstrate that Ia afferent-evoked reciprocal inhibition is as effective at blocking antagonist motor neuron activation at birth as at 1 wk postnatally. In contrast, at birth conditioning stimulation of muscle nerve afferents failed to evoke presynaptic inhibition sufficient to block functional transmission at synapses between Ia afferents and motor neurons, even though dorsal root potentials could be evoked by stimulating the neighboring dorsal root. Presynaptic inhibition at this synapse was readily observed, however, at the end of the first postnatal week. These results indicate Ia afferent feedback from the periphery to central spinal circuits is only weakly gated at birth, which may provide enhanced sensitivity to peripheral feedback during early postnatal experiences.


1991 ◽  
Vol 69 (10) ◽  
pp. 1428-1435
Author(s):  
Parveen Bawa

The effects of tetanic stimulation of peripheral afferents were examined on monosynaptic reflexes and dorsal root reflexes in kittens of various ages. Concomitantly recorded monosynaptic and dorsal root reflexes resulting from the stimulation of muscle nerves showed similar post-tetanic changes, namely, predominantly post-tetanic depression in neonates and post-tetanic potentiation in older kittens or adults. However, the changes in post-tetanic responses expressed as a percentage of control in dorsal root reflexes were much smaller than those in monosynaptic reflexes. When dorsal root reflexes originating from muscle and cutaneous afferents were compared, dorsal root reflexes from the latter behaved quite differently. For all ages, post-tetanic effects on dorsal root reflexes arising from cutaneous afferents were either insignificant or very small. The possible mechanisms underlying differences in post-tetanic effects from muscle and cutaneous afferents in adults and neonates are discussed.Key words: cat, kitten, development, dorsal root reflex, monosynaptic reflex, spinal cord, post-tetanic potentiation.


1983 ◽  
Vol 262 (2) ◽  
pp. 299-302 ◽  
Author(s):  
F.J. Liuzzi ◽  
M.S. Beattie ◽  
J.C. Breshnahan

1993 ◽  
Vol 69 (2) ◽  
pp. 533-544 ◽  
Author(s):  
K. J. Berkley ◽  
A. Robbins ◽  
Y. Sato

1. The uterus, cervix, and vaginal canal are innervated by afferent fibers in the hypogastric and pelvic nerves. Four studies compared the innervation territory and sensitivity to peripheral stimuli of the two sets of fibers in adult virgin rats. 2. Innervation territory was studied anatomically by injecting different fluorescent dyes into different parts of the reproductive, lower urinary, and lower digestive tracts and examining retrogradely labeled neurons in dorsal root ganglia. It was also studied electrophysiologically in anesthetized rats by summing potentials evoked in branches of the two nerves by electrical stimulation of different parts of the reproductive tract. 3. In both studies sensory innervation of the reproductive tract shifted from the pelvic to the hypogastric nerve (i.e., shifted entry into the spinal cord from the L6-S1 to the T13-L3 dorsal root ganglia, respectively) as the dye or stimulating electrode shifted from the vaginal entrance to the uterine horns, with fibers from both nerves densely innervating the cervix region (i.e., entering the spinal cord through both sets of ganglia). The anatomic results suggested that the regions innervated by fibers in one nerve might also be innervated by a small component of normally quiescent fibers in the other nerve. 4. Response sensitivity was studied electrophysiologically by simultaneously recording multiunit activity in branches of the hypogastric and pelvic nerves in two ways. First, in intact, anesthetized rats, activity was recorded during mechanical stimulation of the reproductive tract (distension of the vagina and uterus, probing the cervix). Second, in an in vitro organ preparation of the uterus and vagina, activity was recorded during chemical stimulation through the uterine artery with bradykinin, serotonin, NaCN, CO2, and KCl. 5. Pelvic nerve fibers were markedly more sensitive than hypogastric nerve fibers to uterine and cervical mechanostimulation. Similarly, pelvic nerve fibers were more likely to respond or responded more vigorously than hypogastric nerve fibers to all chemical stimuli (except KCl). 6. These results provide strong evidence that afferent fibers in the pelvic and hypogastric nerves of nulliparous adult rats subserve different functions in reproduction and sensation. Pelvic nerve fibers seem closely tied to sensory and behavioral processes associated with mating and conception, whereas hypogastric fibers seem closely tied to pregnancy and nociception, with fibers in both nerves serving functions during parturition.


2021 ◽  
Author(s):  
Menghon Cheah ◽  
Yuyan Cheng ◽  
Veselina Petrova ◽  
Anda Cimpean ◽  
Pavla Jendelova ◽  
...  

The peripheral branch of sensory dorsal root ganglion (DRG) neurons regenerates readily after injury unlike their central branch in the spinal cord. However extensive regeneration and reconnection of sensory axons in the spinal cord can be driven by the expression of α9 integrin and its activator kindlin-1(α9k1), which enable axons to interact with tenascin-C. To elucidate the mechanisms and downstream pathways affected by activated integrin expression and central regeneration, we conducted transcriptomic analyses of DRG sensory neurons transduced with α9k1, and controls, with and without axotomy of the central branch. Expression of α9k1 without the central axotomy led to upregulation of a known PNS regeneration program, including many genes associated with peripheral nerve regeneration. Coupling α9k1 treatment with dorsal root axotomy led to extensive central axonal regeneration and caused expression of a distinctive CNS regeneration program, including genes associated with ubiquitination, autophagy, endoplasmic reticulum, trafficking, and signalling. Pharmacological inhibition of these processes blocked the regeneration of axons from DRGs and human iPS-derived sensory neurons, validating their causal contributions. This CNS regeneration-associated program showed little correlation with either embryonic development or PNS regeneration programs. Potential transcriptional drivers of this CNS program coupled to regeneration include Mef2a, Runx3, E2f4, Tfeb, Yy1. Signalling from integrins primes sensory neurons for regeneration, but their axon growth in the CNS is associated with a distinctive program that differs from that involved in PNS regeneration.


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