Differential Plasticity of the GABAergic and Glycinergic Synaptic Transmission to Rat Lumbar Motoneurons after Spinal Cord Injury

Abstract

Maturation of inhibitory postsynaptic transmission onto motoneurons in the rat occurs during the perinatal period, a time window during which pathways arising from the brainstem reach the lumbar enlargement of the spinal cord. There is a developmental switch in miniature IPSCs (mIPSCs) from predominantly long-duration GABAergic to short-duration glycinergic events. We investigated the effects of a complete neonatal [postnatal day 0 (P0)] spinal cord transection (SCT) on the expression of Glycine and GABA A receptor subunits (GlyR and GABA A R subunits) in lumbar motoneurons. In control rats, the density of GlyR increased from P1 to P7 to reach a plateau, whereas that of GABA A R subunits dropped during the same period. In P7 animals with neonatal SCT (SCT-P7), the GlyR densities were unchanged compared with controls of the same age, while the developmental downregulation of GABA A R was prevented. Whole-cell patch-clamp recordings of mIPSCs performed in lumbar motoneurons at P7 revealed that the decay time constant of miniature IPSCs and the proportion of GABAergic events significantly increased after SCT. After daily injections of the 5-HT 2 R agonist DOI, GABA A R immunolabeling on SCT-P7 motoneurons dropped down to values reported in control-P7, while GlyR labeling remained stable. A SCT made at P5 significantly upregulated the expression of GABA A R 1 week later with little, if any, influence on GlyR. We conclude that the plasticity of GlyR is independent of supraspinal influences whereas that of GABA A R is markedly influenced by descending pathways, in particular serotoninergic projections.

Characterization of last‐order premotor interneurons by transneuronal tracing with rabies virus in the neonatal mouse spinal cord

“…We focused on glycinergic loINs, which are almost exclusively ipsilateral (94%) and are distributed all along the lumbar segments. The nonglycinergic loINs were likely excitatory or c-aminobutyric acid (GABA)ergic, because GABAergic INs are still detected in the ventral horn during the first few days following birth (Restrepo et al, 2009), and disappear later (Dougherty et al, 2009), in agreement with Figure 5 a decrease of the GABA A receptors observed on TS MNs during the first postnatal week (Sadlaoud et al, 2010). A number of glycinergic loINs, such as RCs, may also express GABA (Jonas et al, 1998;Gao et al, 2001;Alvarez and Fyffe, 2007).…”

Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2

“…Another set of animals was treated chronically with DOI from P4 to P6-P7 [0.15 mg/kg, i.p. (15,20) twice a day]. E IPSP was more hyperpolarized in those DOI-treated animals than in untreated transected animals (Fig.…”

“…1G]. GlyRs are colocalized with the anchoring protein gephyrin and can, therefore, be used to label the plasma membrane; in addition, they are not affected by a neonatal spinal cord transection (20). We, therefore, immunolabeled the α1 subunit of this receptor to visualize the plasma membrane of motoneurons in control (intact), untreated (SCI), and DOItreated cord-transected animals (SCI + DOI; Fig.…”

Sodium-Mediated Plateau Potentials in Lumbar Motoneurons of Neonatal Rats

“…The procedure to label motoneurons before slice preparation was previously described in detail (Sadlaoud et al, 2010). Briefly, in cryoanesthetized rat pups, 5 l of a solution of fluorescein-conjugated cholera toxin B subunit (Invitrogen, 0.5 mg/ml) was injected bilaterally into the triceps surae muscles to retrogradely label gastrocnemius and soleus motoneuron pools.…”