The Effect of DOPA on the Spinal Cord 3. Depolarization Evoked in the Central Terminals of Ipsilateral Ia Afferents by Volleys in the Flexor Reflex Afferents

The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds with high affinity to [mono[125I]iodo-Tyr26]galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that M40 (1 microM) displaces [mono[125I]iodo-Tyr26]galanin from binding sites in the hippocampus, hypothalamus, and spinal cord. In the brain, M40 acts as a potent galanin-receptor antagonist: M40, in doses comparable to that of galanin, antagonizes the stimulatory effects of galanin on feeding, and it blocks the galaninergic inhibition of the scopolamine-induced acetylcholine release in the ventral hippocampus in vivo. In contrast, M40 completely fails to antagonize both the galanin-mediated inhibition of the glucose-induced insulin release in isolated mouse pancreatic islets and the inhibitory effects of galanin on the forskolin-stimulated accumulation of 3',5'-cAMP in Rin m5F cells; instead M40 is a weak agonist at the galanin receptors in these two systems. M40 acts as a weak antagonist of galanin in the spinal flexor reflex model. These results suggest that at least two subtypes of the galanin receptor may exist. Hypothalamic and hippocampal galanin receptors represent a putative central galanin-receptor subtype (GL-1-receptor) that is blocked by M40. The pancreatic galanin receptor may represent another subtype (GL-2-receptor) that recognizes M40, but as a weak agonist. The galanin receptors in the spinal cord occupy an intermediate position between these two putative subtypes.

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INPUT-OUTPUT RELATION IN A FLEXOR REFLEX

The Journal of General Physiology ◽

10.1085/jgp.41.2.297 ◽

1957 ◽

Vol 41 (2) ◽

pp. 297-306 ◽

Cited By ~ 10

Author(s):

David P. C. Lloyd

Keyword(s):

Spinal Cord ◽

Afferent Input ◽

Surprising Result ◽

Input Output ◽

Flexor Reflex ◽

Afferent Fibers ◽

Closed Chain ◽

Central Paths ◽

Reflex Threshold ◽

Reflex Discharge

Observations have been made upon a typical flexor reflex with the aim of disclosing the changes in amount, latency, and temporal configuration of reflex discharge that take place as afferent input is varied from zero to maximal for the band of cutaneous myelinated afferent fibers that extends upward from approximately 6 µ in diameter (group II fibers). Reflex threshold is reached at 6 to 12 per cent maximal afferent input. From threshold to maximal input the relation between input and amount of output is essentially linear, latency on the average decreases, the shorter central paths in general gain preference, but the known minimum pathway, one of three neurons, does not transmit unless aided by convergent activity. Flexor reflex discharge may occur in several bursts suggesting the existence of closed chain connections in the internuncial pools of the spinal cord. At any given input there is, in successively elicited reflexes, little correlation between latency and amount of discharge, at first sight a surprising result for each variable can be taken as a measure of excitability status of the motoneuron population. However, latency of discharge indicates excitability at the beginning of the reflex event whereas amount of discharge is an expression of excitability over the entire period of discharge. Given a constantly and rapidly fluctuating excitability absence of correlation between these variables would be an anticipated result.

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Early postnatal development of GABAergic presynaptic inhibition of Ia proprioceptive afferent connections in mouse spinal cord

Journal of Neurophysiology ◽

10.1152/jn.00783.2012 ◽

2013 ◽

Vol 109 (8) ◽

pp. 2118-2128 ◽

Cited By ~ 9

Author(s):

Patrick M. Sonner ◽

David R. Ladle

Keyword(s):

Spinal Cord ◽

Postnatal Development ◽

Presynaptic Inhibition ◽

Dorsal Root ◽

Reciprocal Inhibition ◽

Afferent Feedback ◽

Early Postnatal Development ◽

Ia Afferent ◽

Ia Afferents ◽

Stimulation Of

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.

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Restless legs syndrome from the spinal cord perspective: A flexor reflex circuitopathy?

Journal of Sleep Research ◽

10.1111/jsr.12704 ◽

2018 ◽

Vol 27 (5) ◽

pp. e12704

Author(s):

Franco Gemignani

Keyword(s):

Spinal Cord ◽

Restless Legs Syndrome ◽

Flexor Reflex ◽

Restless Legs

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Selectivity and excitability of upper-limb muscle activation during cervical transcutaneous spinal cord stimulation in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00132.2021 ◽

2021 ◽

Author(s):

Roberto M. de Freitas ◽

Atsushi Sasaki ◽

Dimitry G. Sayenko ◽

Yohei Masugi ◽

Taishin Nomura ◽

...

Keyword(s):

Spinal Cord ◽

Upper Limb ◽

Spinal Cord Stimulation ◽

Muscle Activation ◽

Anterior Neck ◽

Hand Muscles ◽

Ia Afferents ◽

Arm Muscles ◽

Muscle Responses ◽

Transcutaneous Spinal Cord Stimulation

Cervical transcutaneous spinal cord stimulation (tSCS) efficacy for rehabilitation of upper-limb motor function was suggested to depend on recruitment of Ia afferents. However, selectivity and excitability of motor activation with different electrode configurations remains unclear. In this study, activation of upper-limb motor pools was examined with different cathode and anode configurations during cervical tSCS in 10 able-bodied individuals. Muscle responses were measured from six upper-limb muscles simultaneously. First, post-activation depression was confirmed with tSCS paired pulses (50 ms interval) for each cathode configuration (C6, C7, and T1 vertebral levels), with anode on the anterior neck. Selectivity and excitability of activation of the upper-limb motor pools were examined by comparing the recruitment curves (10-100 mA) of first evoked responses across muscles and cathode configurations. Our results showed that hand muscles were preferentially activated when the cathode was placed over T1 compared to the other vertebral levels, while there was no selectivity for proximal arm muscles. Furthermore, higher stimulation intensities were required to activate distal hand muscles than proximal arm muscles, suggesting different excitability thresholds between muscles. In a separate protocol, responses were compared between anode configurations (anterior neck, shoulders, iliac crests, and back), with one selected cathode configuration. The level of discomfort was also assessed. Largest muscle responses were elicited with the anode configuration over the anterior neck, while there were no differences in the discomfort. Our results therefore inform methodological considerations for electrode configuration to help optimize recruitment of Ia afferents during cervical tSCS.

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