Intersegmental Interactions Give Rise to a Global Network.

Animal motor behaviors require the coordination of different body segments. Thus the activity of the networks that control each segment, which are distributed along the nerve cord, should be adequately matched in time. This temporal organization may depend on signals originated in the brain, the periphery or other segments. Here we evaluate the role of intersegmental interactions. Because of the relatively regular anatomy of leeches, the study of intersegmental coordination in these animals restricts the analysis to interactions among iterated units. We focused on crawling, a rhythmic locomotive behavior through which leeches move on solid ground. The motor pattern was studied ex vivo, in isolated ganglia and chains of three ganglia, and in vivo. Fictive crawling ex vivo (crawling) displayed rhythmic characteristics similar to those observed in vivo. Within the three-ganglion chains the motor output presented an anterior-posterior order, revealing the existence of a coordination mechanism that occurred in the absence of brain or peripheral signals. An experimental perturbation that reversibly abolished the motor pattern in isolated ganglia produced only a marginal effect on the motor activity recorded in three-ganglion chains. Therefore, the segmental central pattern generators present in each ganglion of the chain lost the autonomy observed in isolated ganglia, and constituted a global network that reduced the degrees of freedom of the system. However, the intersegmental phase lag in the three-ganglion chains was markedly longer than in vivo. This work suggests that intersegmental interactions operate as a backbone of correlated motor activity, but additional signals are required to enhance and speed coordination in the animal.

Developmental Synaptic Changes at the Transient Olivocochlear-Inner Hair Cell Synapse.

In the mature mammalian cochlea, inner hair cells (IHCs) are mainly innervated by afferent fibers that convey sound information to the CNS. During postnatal development, however, medial olivocochlear (MOC) efferent fibers transiently innervate the IHCs. The MOC-IHC synapse, functional from postnatal day 0 (P0) to hearing onset (P12), undergoes dramatic changes in the sensitivity to acetylcholine (ACh) and in the expression of key postsynaptic proteins. To evaluate whether there are associated changes in the properties of ACh release during this period, we used a cochlear preparation from mice of either sex at P4, P6-P7, and P9-P11 and monitored transmitter release from MOC terminals in voltage-clamped IHCs in the whole-cell configuration. The quantum content increased 5.6× from P4 to P9-P11 due to increases in the size and replenishment rate of the readily releasable pool of synaptic vesicles without changes in their probability of release or quantum size. This strengthening in transmission was accompanied by changes in short-term plasticity properties, which switched from facilitation at P4 to depression at P9-P11. We have previously shown that at P9-P11, ACh release is supported by P/Q- and N-type voltage-gated calcium channels (VGCCs) and negatively regulated by BK potassium channels activated by Ca2+ influx through L-type VGCCs. We now show that at P4 and P6-P7, release is mediated by P/Q-, R- and L-type VGCCs. Interestingly, L-type VGCCs have a dual role: they both support release and fuel BK channels, suggesting that at immature stages presynaptic proteins involved in release are less compartmentalized.SIGNIFICANCE STATEMENT During postnatal development before the onset of hearing, cochlear inner hair cells (IHCs) present spontaneous Ca2+ action potentials that release glutamate at the first auditory synapse in the absence of sound stimulation. The IHC Ca2+ action potential frequency pattern, which is crucial for the correct establishment and function of the auditory system, is regulated by the efferent medial olivocochlear (MOC) system that transiently innervates IHCs during this period. We show here that developmental changes in synaptic strength and synaptic plasticity properties at the MOC-IHC synapse upon MOC fiber activation at different frequencies might be crucial for tightly shaping the pattern of afferent activity during this critical period.