Pre‐ and postsynaptic modulation of monosynaptic reflex by GABA_A receptors on turtle spinal cord

Abstract

There is growing evidence that activation of high affinity extrasynaptic GABA A receptors in the brain, cerebellum and spinal cord substantia gelatinosa results in a tonic inhibition controlling postsynaptic excitability. The aim of the present study was to determine if GABA A receptors mediating tonic inhibition participate in the modulation of monosynaptic reflex (MSR) in the vertebrate spinal cord. Using an in vitro turtle lumbar spinal cord preparation, we show that conditioning stimulation of a dorsal root depressed the test monosynaptic reflex (MSR) at long condition-test intervals. This long duration inhibition is similar to the one seen in mammalian spinal cord and it is dependent on GABA A as it was completely blocked by 20 μm picrotoxin (PTX) or bicuculline (BIC) or 1 μm gabazine, simultaneously depressing the dorsal root potential (DRP) without MSR facilitation. Interestingly 100 μm picrotoxin or BIC potentiated the MSR, depressed the DRP, and produced a long lasting motoneurone after-discharge. Furosemide, a selective antagonist of extrasynaptic GABA A receptors, affects receptor subtypes with α 4/6 subunits, and in a similar way to higher concentrations of PTX or BIC, also potentiated the MSR but did not affect the DRP, suggesting the presence of α 4/6 GABA A receptors at motoneurones. Our results suggest that (1) the turtle spinal cord has a GABA A mediated long duration inhibition similar to presynaptic inhibition observed in mammals, (2) GABA A receptors located at the motoneurones and primary afferents might produce tonic inhibition of monosynaptic reflex, and (3) GABA A receptors modulate motoneurone excitability reducing the probability of spurious and inappropriate activation.

GABA is a modulator, rather than a classical transmitter, in the medial nucleus of the trapezoid body–lateral superior olive sound localization circuit

“…; Salin & Prince, ; Bautista et al . ), yet the impact varies across brain region and cell type (Lee & Maguire, ). Moreover, tonic activation does not necessarily imply tonic inhibition and spike suppression.…”

“…Tonic activation of extrasynaptic GABA A Rs regulates neuronal excitability (Otis et al 1991;Salin & Prince, 1996;Bautista et al 2010), yet the impact varies across brain region and cell type (Lee & Maguire, 2014). Moreover, tonic activation does not necessarily imply tonic inhibition and spike suppression.…”

Extrasynaptic α6 Subunit-Containing GABAA Receptors Modulate Excitability in Turtle Spinal Motoneurons

“…Previously, we reported that the monosynaptic reflex evoked by electrical stimulation of one dorsal root in the adult turtle spinal cord was facilitated by furosemide without affecting the dorsal root potential [15] . Knowing that furosemide increases the excitability of cerebellar granule cells by blocking extrasynaptic α 6 subunit-containing GABA A receptors [8] , [9] , [20] , [21] , we decided to test whether the facilitation of the monosynaptic reflex was mediated by a similar mechanism in motoneurons.…”

“…Previously we showed that motoneuron excitability might be modulated by high affinity GABA A receptors mediating a tonic inhibitory current [14] , [16] , and that the monosynaptic reflex is facilitated by furosemide without affecting the dorsal root potential [15] . Taken together, these results suggested the presence of furosemide-sensitive GABA A receptors in motoneurons.…”

“…In addition, we found that blockade of GABA A receptors with low concentrations (1–20 µM) of picrotoxin and gabazine reverted presynaptic inhibition of primary afferents without facilitating the MSR, but depressing the dorsal root potential (DRP). However, when picrotoxin concentration was increased to 100 µM, the MSR was facilitated producing a long lasting activation of some motoneurons accompanied with an additional depression of the DRP [15] .…”