Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord

Mentis, George Z.; Álvarez, Francisco J.; Bonnot, Agnès; Richards, Dannette Shanon; González-Forero, David; Zerda, Ricardo; O’Donovan, Michael J.

doi:10.1073/pnas.0502788102

Cited by 152 publications

(213 citation statements)

References 43 publications

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“…The results are in agreement with findings of glutamatergic transmission at adult vertebrate NMJs (34) and with the release of glutamate from neonatal mammalian motorneurons (35,36). Glutamatergic-cholinergic cotransmission at the vertebrate NMJ may contribute to apparently normal behavioral and physiological development after chronic blockade of embryonic electrical activity (37,38).…”

Section: Discussionsupporting

confidence: 89%

Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction

Borodinsky

Spitzer

2007

Proc. Natl. Acad. Sci. U.S.A.

109

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Signaling in the nervous system requires matching of neurotransmitter receptors with cognate neurotransmitters at synapses. The vertebrate neuromuscular junction is the best studied cholinergic synapse, but the mechanisms by which acetylcholine is matched with acetylcholine receptors are not fully understood. Because alterations in neuronal calcium spike activity alter transmitter specification in embryonic spinal neurons, we hypothesized that receptor expression in postsynaptic cells follows changes in transmitter expression to achieve this specific match. We find that embryonic vertebrate striated muscle cells normally express receptors for glutamate, GABA, and glycine as well as for acetylcholine. As maturation progresses, acetylcholine receptor expression prevails. Receptor selection is altered when early neuronal calcium-dependent activity is perturbed, and remaining receptor populations parallel changes in transmitter phenotype. In these cases, glutamatergic, GABAergic, and glycinergic synaptic currents are recorded from muscle cells, demonstrating that activity regulates matching of transmitters and their receptors in the assembly of functional synapses.

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Section: Discussionsupporting

confidence: 89%

Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction

Borodinsky

Spitzer

2007

Proc. Natl. Acad. Sci. U.S.A.

109

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“…We also observed highfrequency bursting after ventral root stimulation (Fig. 1 D), a hallmark of RCs as demonstrated in previous studies from both adult and immature animals (Renshaw, 1946;Eccles et al, 1954;Naka, 1964;Mentis et al, 2005).…”

Section: Identification Of Rcssupporting

confidence: 88%

“…GFP-positive cells in the ventral cord were visually patched in the L2 (Fig. 1 B, C) and were identified as RCs by electrically stimulating the L2 ventral root to evoke short-latency EPSPs, which were mostly blocked by bath application of the nicotinic receptor antagonists mecamylamine or tubocurarine (Mentis et al, 2005;Nishimaru et al, 2005). Some cells were also filled with Alexa Fluor dyes to confirm their expression of calbindin 28k after recording (Nishimaru et al, 2005).…”

Section: Identification Of Rcsmentioning

confidence: 99%

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Activity of Renshaw Cells during Locomotor-Like Rhythmic Activity in the Isolated Spinal Cord of Neonatal Mice

Nishimaru¹,

Restrepo²,

Kiehn³

2006

J. Neurosci.

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In the present study, we examine the activity patterns of and synaptic inputs to Renshaw cells (RCs) during fictive locomotion in the newborn mouse using visually guided recordings from GABAergic cells expressing glutamic acid decarboxylase 67-green fluorescent protein (GFP). Among the GFP-positive neurons in the lumbar ventral horn, RCs were uniquely identified as receiving ventral rootevoked short-latency EPSPs that were markedly reduced in amplitude by nicotinic receptor blockers mecamylamine or tubocurarine. During locomotor-like rhythmic activity evoked by bath application of 5-HT and NMDA, 50% of the recorded RCs fired in-phase with the ipsilateral L2 flexor-related rhythm, whereas the rest fired in the extensor phase. Each population of RCs fired throughout the corresponding locomotor phase. All RCs received both excitatory and inhibitory synaptic inputs during the locomotor-like rhythmic activity. Blocking nicotinic receptors with mecamylamine markedly reduced the rhythmic excitatory drive, indicating that these rhythmic inputs originate mainly from motor neurons (MNs). Inhibitory synaptic inputs persisted in the presence of the nicotinic blocker. Part of this inhibitory drive and remaining excitatory drive could be from commissural interneurons because the present study also shows that RCs receive direct crossed inhibitory and excitatory synaptic inputs. However, rhythmic synaptic inputs in RCs were also observed in hemicord preparations in the presence of mecamylamine. These results show that, during locomotor activity, RC firing properties are modulated not only by MNs but also by the ipsilateral and contralateral locomotor networks.

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“…VAChT, which packages acetylcholine into synaptic vesicles for exocytosis, is an effective synaptic marker of motor axon synapses on RCs but there are additional sources of VAChT-IR synapses in the ventral horn Mentis et al, 2005;Miles et al, 2007;Zagoraiou et al, 2009). Some VAChT-IR contacts were observed on V1-IaIN dendrites at P20 ; therefore, we investigated their origins and the possibility that this input, similar to the VGLUT1 input on RCs, was initially stronger in neonatal V1-IaINs and then deselected ( Fig.…”

Section: Vacht-ir Bouton Density On V1-iains Is Lower Than On Rcs Of mentioning

confidence: 99%

Target selection of proprioceptive and motor axon synapses on neonatal V1‐derived Ia inhibitory interneurons and Renshaw cells

Siembab

Smith

Zagoraiou

et al. 2010

J of Comparative Neurology

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The diversity of premotor interneurons in the mammalian spinal cord is generated from a few phylogenetically conserved embryonic classes of interneurons (V0, V1, V2, V3). Their mechanisms of diversification remain unresolved, although these are clearly important to understand motor circuit assembly in the spinal cord. Some Ia inhibitory interneurons (IaINs) and all Renshaw cells (RCs) derive from embryonic V1 interneurons; however, in adult they display distinct functional properties and synaptic inputs, for example proprioceptive inputs preferentially target IaINs, while motor axons target RCs. Previously, we found that both inputs converge on RCs in neonates, raising the possibility that proprioceptive (VGLUT1-positive) and motor axon synapses (VAChT-positive) initially target several different V1 interneurons populations and then become selected or deselected postnatally. Alternatively, specific inputs might precisely connect only with predefined groups of V1 interneurons. To test these hypotheses we analyzed synaptic development on V1-derived IaINs and compared them to RCs of the same age and spinal cord levels. V1-interneurons were labeled using genetically encoded lineage markers in mice. The results show that although neonatal V1-derived IaINs and RCs are competent to receive proprioceptive synapses, these synapses preferentially target the proximal somato-dendritic regions of IaINs and postnatally proliferate on IaINs, but not on RCs. In contrast, cholinergic synapses on RCs are specifically derived from motor axons, while on IaINs they originate from Pitx2 V0c interneurons. Thus, motor, proprioceptive, and even some interneuron inputs are biased toward specific subtypes of V1-interneurons. Postnatal strengthening of these inputs is later superimposed on this initial preferential targeting. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe development of spinal cord local interneuronal circuits is currently poorly understood. Recent work has defined a relatively small number of cardinal interneurons in embryo that generates the much larger diversity of adult interneurons (Goulding, 2009). In the ventral horn just four embryonic subgroups (V0, V1, V2, V3) generate most adult premotor interneurons by diversification mechanisms that are currently largely unknown. Each group displays common properties that generally include origins from one type of progenitor cell (p0, p1, p2, p3), the direction taken by the primary axon, their cell migration and final location in the ventral horn with relation to motor pools, and their neurotransmitter phenotype. For example, V1 interneurons have common origins in the p1 progenitor area and are characterized by expression of the engrailed-1 (En-1) transcription factor. They migrate ventrolaterally, positioning themselves adjacent to motor pools, extend ascending axons that target ipsilateral motoneurons, and have an inhibitory phenotype (Matise and Joyner, 1997; Ericsson et al., 1997;Saueressig et al., 1999;Sapir et al., 2004;Alvarez et a...

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Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord

Cited by 152 publications

References 43 publications

Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction

Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction

Activity of Renshaw Cells during Locomotor-Like Rhythmic Activity in the Isolated Spinal Cord of Neonatal Mice

Target selection of proprioceptive and motor axon synapses on neonatal V1‐derived Ia inhibitory interneurons and Renshaw cells

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