Neural Activity During The Formation Of A Giant Auditory Synapse

The formation of synapses is a critical step in the development of the brain. During this developmental stage neural activity propagates across the brain from synapse to synapse. This activity is thought to instruct the precise, topological connectivity found in the sensory central nervous system. In the General Introduction some possible hypotheses for establishing topological connectivity in the brain are put forward. In this thesis I demonstrated that during the period when a giant auditory synapse is formed, the calyx of Held synapse, including both the calyx itself and its postsynaptic target, the principal neuron of the medial nucleus of the trapezoid body, displays bursts of neural firing. With our unique in vivo approach I describe in CHAPTER 2 the patterns of neural activity at the calyx of Held in neonatal rats. Despite the young age of the pup and the early stage of calyx development, very brief intervals between action potentials (APs) were observed with only minor changes in the shape of the calyceal AP. One of the processes that keeps the AP shape invariant was related to the absolute membrane potential attained following the AP, the after-potential. I propose that there might be an essential role for the after-potential to stabilize the AP shape in high frequency firing. In CHAPTER 3 I focus on the developmental changes in the calyx of Held synapse and the postsynaptic neuron. In a few days a relay synapse emerges that reliably drives postsynaptic activity. The other synaptic inputs become less relevant for postsynaptic firing, because of changes in the intrinsic properties of the postsynaptic neuron. I demonstrate a clear correlation between the postsynaptic excitability and the emergence of the relay synapse, possibly indicating a homeostatic matching of the size of the inputs and the size of the input resistance. In the days prior to the appearance of the relay synapse, the activity of many converging synapses caused a continuous depolarization. By means of modeling I suggest that this depolarization only helps to trigger postsynaptic APs in the period before the relay synapse emerges, as an increase in low-threshold potassium channels precluded the triggering of postsynaptic APs by slowly-rising, prolonged depolarizations at the later developmental stages. From the many terminals that connect to a principal neuron in neonatal rats, typically a single calyx of Held remains in the adult. During this period I expected that multiple calyces would initially form on a principal cell followed by the selection of a single ‘winner’ calyx of Held, as indicated by some other studies. In CHAPTER 4 I describe in detail that we do not observe electrophysiological evidence for multiple calyceal innervations. Weak inputs were present throughout this period. While the strongest input became stronger, the second strongest input retained its strength. Our attempt to retrieve the morphology of the terminals that are formed on the recorded neuron did not reveal a clear mismatch between our electrophysiological recordings and the terminal. I propose some possible explanations for the apparent discrepancy between previous studies and my findings. In the end, either multiple calyces are rarely formed on single rat principal cells or they are very weak for the

cAMP-Dependent Co-stabilization of Axonal Arbors from Adjacent Developing Neurons

Axonal arbors in many neuronal networks are exuberant early during development and become refined by activity-dependent competitive mechanisms. Theoretical work proposed non-competitive interactions between co-active axons to co-stabilize their connections, but the demonstration of such interactions is lacking. Here, we provide experimental evidence that reducing cyclic AMP (cAMP) signaling in a subset of retinal ganglion cells favors the elimination of thalamic projections from neighboring neurons, pointing to a cAMP-dependent interaction that promotes axon stabilization

Resistance to action potential depression of a rat axon terminal in vivo

The shape of the presynaptic action potential (AP) has a strong impact on neurotransmitter release. Because of the small size of most terminals in the central nervous system, little is known about the regulation of their AP shape during natural firing patterns in vivo. The calyx of Held is a giant axosomatic terminal in the auditory brainstem, whose biophysical properties have been well studied in slices. Here, we made whole-cell recordings from calyceal terminals in newborn rat pups. The calyx showed a characteristic burst firing pattern, which has previously been shown to originate from the cochlea. Surprisingly, even for frequencies over 200 Hz, the AP showed little or no depression. Current injections showed that the rate of rise of the AP depended strongly on its onset potential, and that the membrane potential after the AP (Vafter) was close to the value at which no depression would occur during high-frequency activity. Immunolabeling revealed that Nav1.6 is already present at the calyx shortly after its formation, which was in line with the fast recovery from AP depression that we observed in slice recordings. Our findings thus indicate that fast recovery from depression and an inter-AP membrane potential that minimizes changes on the next AP in vivo, together enable high timing precision of the calyx of Held already shortly after its formation

Structure–function relation of the developing calyx of Held synapse in vivo

Key points: During development the giant, auditory calyx of Held forms a one-to-one connection with a principal neuron of the medial nucleus of the trapezoid body. While anatomical studies described that most of the target cells are temporarily contacted by multiple calyces, multi-calyceal innervation was only sporadically observed in in vivo recordings, suggesting a structure–function discrepancy. We correlated synaptic strength of inputs, identified in in vivo recordings, with post hoc labelling of the recorded neuron and synaptic terminals containing vesicular glutamate transporters (VGluT). During development only one input increased to the level of the calyx of Held synapse, and its strength correlated with the large VGluT cluster contacting the postsynaptic soma. As neither competing strong inputs nor multiple large VGluT clusters on a single cell were observed, our findings did not indicate a structure–function discrepancy. Abstract: In adult rodents, a principal neuron in the medial nucleus of the trapezoid (MNTB) is generally contacted by a single, giant axosomatic terminal called the calyx of Held. How this one-on-one relation is established is still unknown, but anatomical evidence suggests that during development principal neurons are innervated by multiple calyces, which may indicate calyceal competition. However, in vivo electrophysiological recordings from principal neurons indicated that only a single strong synaptic connection forms per cell. To test whether a mismatch exists between synaptic strength and terminal size, we compared the strength of synaptic inputs with the morphology of the synaptic terminals. In vivo whole-cell recordings of the MNTB neurons from newborn Wistar rats of either sex were made while stimulating their afferent axons, allowing us to identify multiple inputs. The strength of the strongest input increased to calyceal levels in a few days across cells, while the strength of the second strongest input was stable. The recorded cells were subsequently immunolabelled for vesicular glutamate transporters (VGluT) to reveal axosomatic terminals with structur

Квитанция по принятию объявление в газету "Вечернее Тбилиси"

Русудан Багратион-Мухранская - дочка Нико Бур