Gap junction-mediated glycinergic inhibition ensures precise temporal patterning in vocal behavior.

Precise neuronal firing is especially important for behaviors highly dependent on the correct sequencing and timing of muscle activity patterns, such as acoustic signaling. Acoustic signaling is an important communication modality for vertebrates, including many teleost fishes. Toadfishes are well known to exhibit high temporal fidelity in synchronous motoneuron firing within a hindbrain network directly determining the temporal structure of natural calls. Here, we investigated how these motoneurons maintain synchronous activation. We show that pronounced temporal precision in population-level motoneuronal firing depends on gap junction-mediated, glycinergic inhibition that generates a period of reduced probability of motoneuron activation. Super-resolution microscopy confirms glycinergic release sites formed by a subset of adjacent premotoneurons contacting motoneuron somata and dendrites. In aggregate, the evidence supports the hypothesis that gap junction-mediated, glycinergic inhibition provides a timing mechanism for achieving synchrony and temporal precision in the millisecond range for rapid modulation of acoustic waveforms.

Distinct roles for inhibition in spatial and temporal tuning of local edge detectors in the rabbit retina.

This paper examines the role of inhibition in generating the receptive-field properties of local edge detector (LED) ganglion cells in the rabbit retina. We confirm that the feed-forward inhibition is largely glycinergic but, contrary to a recent report, our data demonstrate that the glycinergic inhibition contributes to temporal tuning for the OFF and ON inputs to the LEDs by delaying the onset of spiking; this delay was more pronounced for the ON inputs (∼ 340 ms) than the OFF inputs (∼ 12 ms). Blocking glycinergic transmission reduced the delay to spike onset and increased the responses to flickering stimuli at high frequencies. Analysis of the synaptic conductances indicates that glycinergic amacrine cells affect temporal tuning through both postsynaptic inhibition of the LEDs and presynaptic modulation of the bipolar cells that drive the LEDs. The results also confirm that presynaptic GABAergic transmission contributes significantly to the concentric surround antagonism in LEDs; however, unlike presumed LEDs in the mouse retina, the surround is only partly generated by spiking amacrine cells.

Glycinergic and GABAergic control of intensity-response function of frog ERG waves under different conditions of light stimulation.

The effect of glycinergic blockade by strychnine and GABAergic blockade by picrotoxin on the intensity-response function and time course of ERG b- and d-wave was investigated in dark and light adapted frog eyecups as well as in chromatically adapted eyecups, in which the responses were predominantly mediated by one photoreceptor type. Both of the blockers markedly increased the maximal response amplitude and thus increased the contrast gain of the mechanisms generating ERG waves. Strychnine but not picrotoxin narrowed the dynamic range of the b-wave in all eyecups. The glycine and GABAergic control on retinal sensitivity however, depended on photoreceptor input. The b-wave sensitivity was increased to the greatest extent when green rods mediated the response; it was slightly increased when the response was mediated by red cones and was not changed at all when red rods mediated the b-wave. On the other hand the d-wave sensitivity was enhanced regardless of photoreceptor input so that it became equal (dark) or even greater (light adapted eyes) than that of the b-wave. Strychnine shortened but picrotoxin increased the implicit time of the b-wave and both the blockers markedly slowed the d-wave time course. Thus the blockers considerably diminished or fully eliminated the initial difference in time course between the ON and OFF response. The glycine- and GABAergic blockade did not principally alter the light adaptation process expressed in decreasing retinal sensitivity, narrowing the dynamic range and speeding the time course of the responses with increasing background illumination.

Neuronal model of tactile allodynia produced by spinal strychnine: effects of excitatory amino acid receptor antagonists and a mu-opiate receptor agonist.

Touch evoked agitation (allodynia) can be induced by spinal delivery of strychnine and this effect is antagonized by intrathecal NMDA and non-NMDA receptor antagonists, but not by mu-opiate receptor agonists. In this study, we sought to characterize the effect of focal glycine-receptor inhibition on spontaneous and evoked activity in dorsal horn neurons of the chloralose-anesthetized cat. Strychnine (1 mM) applied near the neurons through a dialysis fiber caused an enhanced response to hair deflection, enlargement of the low threshold receptive fields and in some cells, an increase in afterdischarge. These changes were observed only in cells that were activated by both hair deflection and high intensity mechanical stimulation. Subsequent co-administration of an NMDA receptor antagonist (AP-7, 2.0 mM) preferentially blocked strychnine-associated effects without changing the original receptive field characteristics. Co-administration of a non-NMDA excitatory amino acid receptor antagonist (CNQX, 1 mM) with the strychnine served to block low (brush) and high intensity (pinch) afferent input. In contrast, addition of a mu-opiate receptor agonist (alfentanil 2.4 mM) to the strychnine perfusate selectively reduced responsiveness to high intensity stimulation, while having no effect on the exaggerated response to hair deflection. Given the functional and pharmacological similarity of the effects of spinal strychnine to post-nerve injury states in man, disinhibition due to a loss of glycinergic input may be associated with large myelinated fiber-mediated nociceptive states. Consistent with these data is the contention that under normal circumstances, afferent hair follicle input onto convergent neurons is regulated by a tonic glycinergic circuit. Removal of this regulatory influence leads to a magnification of low threshold tactile throughput in dorsal horn. This model may help to provide pharmacological insights into more efficacious treatments for such pain states that are relatively refractory to opioid therapies.