Structural materials in nature exhibit remarkable designs with building blocks, often hierarchically arranged from the nanometer to the macroscopic length scales. We report on the structural properties of biosilica observed in the hexactinellid sponge Euplectella sp. Consolidated, nanometer-scaled silica spheres are arranged in well-defined microscopic concentric rings glued together by organic matrix to form laminated spicules. The assembly of these spicules into bundles, effected by the laminated silica-based cement, results in the formation of a macroscopic cylindrical square-lattice cagelike structure reinforced by diagonal ridges. The ensuing design overcomes the brittleness of its constituent material, glass, and shows outstanding mechanical rigidity and stability. The mechanical benefits of each of seven identified hierarchical levels and their comparison with common mechanical engineering strategies are discussed.

The steep calcium dependence of synaptic strength that has been observed at many synapses is thought to reflect a calcium dependence of the probability of vesicular exocytosis (p), with the cooperativity of three to six corresponding to the multiple calcium ion binding sites on the calcium sensor responsible for exocytosis. Here we test the hypothesis that the calcium dependence of the effective size of the readily-releasable pool (RRP) also contributes to the calcium dependence of release at the calyx of Held synapse in mice. Using two established methods of quantifying neurotransmitter release evoked by action potentials (effective RRP), we find that when calcium influx is changed by altering the external calcium concentration, the calcium cooperativity of p is insufficient to account for the full calcium dependence of EPSC size; the calcium-dependence of the RRP size also contributed. Reducing calcium influx by blocking R-type voltage-gated calcium channels (VGCCs) with Ni2+, or by blocking P/Q-type VGCCs with ω-agatoxin IVA also changes EPSC amplitude by reducing both p and the effective RRP size. This suggests that the effective RRP size is dependent on calcium influx through VGCCs. Furthermore, activation of GABAB receptors, which reduces presynaptic calcium through VGCCs without other significant effects on release, also reduces the effective RRP size in addition to reducing p. These findings indicate that calcium influx regulates the RRP size along with p, this contributes to the calcium dependence of synaptic strength, and it influences the manner in which presynaptic modulation of presynaptic calcium channels affects neurotransmitter release.

Background The specific properties of a synapse determine how neuronal activity evokes neurotransmitter release. Evaluating changes in synaptic properties during sustained activity is essential to understanding how genetic manipulations and neuromodulators regulate neurotransmitter release. Analyses of postsynaptic responses to high-frequency stimulation have provided estimates of the size of the readily-releasable pool (RRP) of vesicles (N0) and the probability of vesicular release (p) at multiple synapses. New Method Here, we introduce a model-based approach at the calyx of Held synapse in which depletion and the rate of replenishment (R) determine the number of available vesicles, and facilitation leads to a use-dependent increase in p when initial p is low. Results When p is high and R is low, we find excellent agreement between estimates based on all three methods and the model. However, when p is low or when significant replenishment occurs between stimuli, estimates of different methods diverge, and model estimates are between the extreme estimates provided by the other approaches. Comparison with Other Methods We compare our model-based approach to three other approaches that rely on different simplifying assumptions. Our findings suggest that our model provides a better estimate of N0 and p than previously-established methods, likely due to inaccurate assumptions about replenishment. More generally, our findings suggest that approaches commonly used to estimate N0 and p at other synapses are often applied under experimental conditions that yield inaccurate estimates. Conclusions Careful application of appropriate methods can greatly improve estimates of synaptic parameters.

Golgi cells (GoCs) are inhibitory interneurons that influence the cerebellar cortical response to sensory input by regulating the excitability of the granule cell layer. While GoC inhibition is essential for normal motor coordination, little is known about the circuit dynamics that govern the activity of these cells. In particular, while GoC spontaneous spiking influences the extent of inhibition and gain throughout the granule cell layer, it is not known whether this spontaneous activity can be modulated in a long-term manner. Here we describe a form of long-term plasticity that regulates the spontaneous firing rate of GoCs in the rat cerebellar cortex. We find that membrane hyperpolarization, either by mGluR2 activation of potassium channels, or by somatic current injection, induces a long-lasting increase in GoC spontaneous firing. This spike rate plasticity appears to result from a strong reduction in the spike afterhyperpolarization (AHP). Pharmacological manipulations suggest the involvement of calcium-calmodulin dependent kinase II (CaMKII) and calcium-activated potassium channels in mediating these firing rate increases. As a consequence of this plasticity, GoC spontaneous spiking is selectively enhanced, but the gain of evoked spiking is unaffected. Hence this plasticity is well-suited for selectively regulating the tonic output of GoCs rather than their sensory-evoked responses.