In vivo matching of postsynaptic excitability with spontaneous synaptic inputs during formation of the rat calyx of Held synapse

Key points: Neurons in the medial nucleus of the trapezoid body of anaesthetized rats of postnatal day (P)2–6 showed burst firing with a preferred interval of about 100 ms, which was stable, and a second preferred interval of 5–30 ms, which shortened during development. In 3 out of 132 cases, evidence for the presence of two large inputs was found. In vivo whole-cell recordings revealed that the excitability of the principal neuron and the size of its largest synaptic inputs were developmentally matched. At P2–4, action potentials were triggered by barrages of small synaptic events that summated to plateau potentials, while at later stages firing depended on a single, large and often prespike-associated input, which is probably the nascent calyx of Held. Simulations with a Hodgkin–Huxley-like model, which was based on fits of the intrinsic postsynaptic properties, suggested an essential role for the low-threshold potassium conductance in this transition. Abstract: In the adult, principal neurons of the medial nucleus of the trapezoid body (MNTB) are typically contacted by a single, giant terminal called the calyx of Held, whereas during early development a principal neuron receives inputs from many axons. How these changes in innervation impact the postsynaptic activity has not yet been studied in vivo. We therefore recorded spontaneous inputs and intrinsic properties of principal neurons in anaesthetized rat pups during the developmental period in which the calyx forms. A characteristic bursting pattern could already be observed at postnatal day (P)2, before formation of the calyx. At this age, action potentials (APs) were triggered by barrages of summating EPSPs causing plateau depolarizations. In contrast, at P5, a single EPSP reliably triggered APs, resulting in a close match between pre- and postsynaptic firing. Postsynaptic excitability and the size of the largest synaptic events were developmentally matched. The developmental changes in intrinsic properties were estimated by fitting in vivo current injections to a Hodgkin–Huxley-type model of the principal neuron. Our simulations indicated that the developmental increases in Ih, low-threshold K+ channels and leak currents contributed to the reduction in postsynaptic excitability, but that low-threshold K+ channels specifically functioned as a dampening influence in the near-threshold range, thus precluding small inputs from triggering APs. Together, these coincident changes help to propagate bursting activity along the auditory brainstem, and are essential steps towards establishing the relay function of the calyx of Held synapse.

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