Comparison of the Inhibition of Renshaw Cells During Subthreshold and Suprathreshold Conditions Using Anatomically and Physiologically Realistic Models

Inhibitory synaptic inputs to Renshaw cells are concentrated on the soma and the juxtasomatic dendrites. In the present study, we investigated whether this proximal bias leads to more effective inhibition under different neuronal operating conditions. Using compartmental models based on detailed anatomical measurements of intracellularly stained Renshaw cells, we compared the inhibition produced by glycine/γ-aminobutyric acid-A (GABAA) synapses when distributed with a proximal bias to the inhibition produced when the same synapses were distributed uniformly (i.e., with no regional bias). The comparison was conducted in subthreshold and suprathreshold conditions. The latter were mimicked by voltage clamping the soma to −55 mV. The voltage clamp reduces nonlinear interactions between excitatory and inhibitory synapses. We hypothesized that for electrotonically compact cells such as Renshaw cells, the strength of the inhibition would become much less dependent on synaptic location in suprathreshold conditions. This hypothesis was not confirmed. The inhibition produced when inhibitory inputs were proximally distributed was always stronger than when the same inputs were uniformly distributed. In fact, the relative effectiveness of proximally distributed inhibitory inputs over uniformly distributed synapses was greater in suprathreshold conditions than that in subthreshold conditions. The somatic voltage clamp minimized saturation of inhibitory driving potentials. Because this effect was greatest near the soma, the current produced by more distal synapses suffered a greater loss because of saturation. Conversely, in subthreshold conditions, the effectiveness of proximal synapses was substantially reduced at high levels of background synaptic activity because of saturation. Our results suggest glycine/GABAA synapses on Renshaw cells are strategically distributed to block the powerful excitatory drive produced by recurrent collaterals from motoneurons.

Development of an Inhibitory Interneuronal Circuit in the Embryonic Spinal Cord

Locally projecting inhibitory interneurons play a crucial role in the patterning and timing of network activity. However, because of their relative inaccessibility, little is known about their development or incorporation into circuits. In this study, we characterized the functional onset, neurotransmitters, rostrocaudal spread, and funicular distribution of one such spinal interneuronal circuit during development. The R-interneuron is the avian homologue of the mammalian Renshaw cell. Both cell types receive input from motoneuron recurrent collaterals and make direct connections back onto motoneurons. By stimulating motoneurons projecting in a given ventral root and recording the response in adjacent ventral roots, we demonstrate that the R-interneuron circuit becomes functional between embryonic day 6 (E6) and E7. This ventral root response is observed at E11 and at E14 until it can no longer be detected at E16. Using bath-applied neurotransmitter receptor antagonists, we were able to demonstrate that the circuit is predominately nicotinic and GABAergic from E7.5 to E15. We also found a glutamatergic component to the pathway throughout this developmental period. The R-interneuron projects three or more segments both rostrally and caudally through the ventrolateral funiculus. The distribution of this circuit may become more locally focused between E7.5 and E15.

Two Dynamically Distinct Inhibitory Networks in Layer 4 of the Neocortex

Normal operations of the neocortex depend critically on several types of inhibitory interneurons, but the specific function of each type is unknown. One possibility is that interneurons are differentially engaged by patterns of activity that vary in frequency and timing. To explore this, we studied the strength and short-term dynamics of chemical synapses interconnecting local excitatory neurons (regular-spiking, or RS, cells) with two types of inhibitory interneurons: fast-spiking (FS) cells, and low-threshold spiking (LTS) cells of layer 4 in the rat barrel cortex. We also tested two other pathways onto the interneurons: thalamocortical connections and recurrent collaterals from corticothalamic projection neurons of layer 6. The excitatory and inhibitory synapses interconnecting RS cells and FS cells were highly reliable in response to single stimuli and displayed strong short-term depression. In contrast, excitatory and inhibitory synapses interconnecting the RS and LTS cells were less reliable when initially activated. Excitatory synapses from RS cells onto LTS cells showed dramatic short-term facilitation, whereas inhibitory synapses made by LTS cells onto RS cells facilitated modestly or slightly depressed. Thalamocortical inputs strongly excited both RS and FS cells but rarely and only weakly contacted LTS cells. Both types of interneurons were strongly excited by facilitating synapses from axon collaterals of corticothalamic neurons. We conclude that there are two parallel but dynamically distinct systems of synaptic inhibition in layer 4 of neocortex, each defined by its intrinsic spiking properties, the short-term plasticity of its chemical synapses, and (as shown previously) an exclusive set of electrical synapses. Because of their unique dynamic properties, each inhibitory network will be recruited by different temporal patterns of cortical activity.

Sensorimotor Integration at the Dorsal Column Nuclei

Interaction among primary afferents, corticofugal fibers, and intrinsic elements allows for sensorimotor integration at the dorsal column nuclei. The interneurons permit the spatial localization, the recurrent collaterals synchronize the activity of projecting cells with overlapping receptive fields, and the corticofugal fibers induce a central zone of activity surrounded by a peripheral zone of inhibition.