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2015 ; 35
(40
): 13673-86
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Synaptic Connectivity between Renshaw Cells and Motoneurons in the Recurrent
Inhibitory Circuit of the Spinal Cord
#MMPMID26446220
Moore NJ
; Bhumbra GS
; Foster JD
; Beato M
J Neurosci
2015[Oct]; 35
(40
): 13673-86
PMID26446220
show ga
Renshaw cells represent a fundamental component of one of the first discovered
neuronal circuits, but their function in motor control has not been established.
They are the only central neurons that receive collateral projections from motor
outputs, yet the efficacy of the excitatory synapses from single and converging
motoneurons remains unknown. Here we present the results of dual whole-cell
recordings from identified, synaptically connected Renshaw cell-motoneuron pairs
in the mouse lumbar spinal cord. The responses from single Renshaw cells
demonstrate that motoneuron synapses elicit large excitatory conductances with
few or no failures. We show that the strong excitatory input from motoneurons
results from a high probability of neurotransmitter release onto multiple
postsynaptic contacts. Dual current-clamp recordings confirm that single
motoneuron inputs were sufficient to depolarize the Renshaw cell beyond threshold
for firing. Reciprocal connectivity was observed in approximately one-third of
the paired recordings tested. Ventral root stimulation was used to evoke currents
from Renshaw cells or motoneurons to characterize responses of single neurons to
the activation of their corresponding presynaptic cell populations. Excitatory or
inhibitory synaptic inputs in the recurrent inhibitory loop induced substantial
effects on the excitability of respective postsynaptic cells. Quantal analysis
estimates showed a large number of converging inputs from presynaptic motoneuron
and Renshaw cell populations. The combination of considerable synaptic efficacy
and extensive connectivity within the recurrent circuitry indicates a role of
Renshaw cells in modulating motor outputs that may be considerably more important
than has been previously supposed. SIGNIFICANCE STATEMENT: We have recently shown
that Renshaw cells mediate powerful shunt inhibition on motoneuron excitability.
Here we complete a quantitative description of the recurrent circuit using
recordings of excitatory synapses between identified motoneuron and Renshaw cell
pairs. We show that the excitation is highly effective as a result of a high
probability of neurotransmitter release onto multiple release sites and that
efficient neurotransmission is maintained at physiologically relevant firing
rates in motoneurons. Our results also show that both excitatory and inhibitory
connections exhibit considerable convergence of inputs. Because evaluation of the
determinants of synaptic strength and the extent of connectivity constitute
fundamental parameters affecting the operation of the recurrent circuit, our
findings are critical for informing any future models of motor control.
|Animals
[MESH]
|Animals, Newborn
[MESH]
|Biophysics
[MESH]
|Calcium/metabolism
[MESH]
|Electric Stimulation
[MESH]
|Female
[MESH]
|Glycine Plasma Membrane Transport Proteins/genetics/metabolism
[MESH]