Controlling Effects of Astrocyte on Neuron Behavior in Tripartite Synapse Using VHDL–AMS

Astrocyte cells form the largest cell population in the brain and can influence neuron behavior. These cells provide appropriate feedback control in regulating neuronal activities in the Central Nervous System (CNS). This paper presents a set of equations as a model to describe the interactions between neurons and astrocyte. A VHDL–AMS-based tripartite synapse model that includes a pre-synaptic neuron, the synaptic terminal, a post-synaptic neuron, and an astrocyte cell is presented. In this model, the astrocyte acts as a controller module for neurons and can regulates the spiking activity of them. Simulation results show that by regulating the coupling coefficients of astrocytes, spiking frequency of neurons can be reduced and the activity of neuronal cells is modulated.

Elevated energy requirement of cone photoreceptors

We have used recent measurements of mammalian cone light responses and voltage-gated currents to calculate cone ATP utilization and compare it to that of rods. The largest expenditure of ATP results from ion transport, particularly from removal of Na+entering outer segment light-dependent channels and inner segment hyperpolarization-activated cyclic nucleotide-gated channels, and from ATP-dependent pumping of Ca2+entering voltage-gated channels at the synaptic terminal. Single cones expend nearly twice as much energy as single rods in darkness, largely because they make more synapses with second-order retinal cells and thus must extrude more Ca2+. In daylight, cone ATP utilization per cell remains high because cones never remain saturated and must continue to export Na+and synaptic Ca2+even in bright illumination. In mouse and human retina, rods greatly outnumber cones and consume more energy overall even in background light. In primates, however, the high density of cones in the fovea produces a pronounced peak of ATP utilization, which becomes particularly prominent in daylight and may make this part of the retina especially sensitive to changes in energy availability.

Evidence of structural and functional plasticity occurring within the intracardiac nervous system of spontaneously hypertensive rats

We have developed intracardiac neuron whole cell recording techniques in atrial preparations from control and spontaneous hypertensive rats. This has enabled the identification of significant synaptic plasticity in the intracardiac nervous system, including enhanced postsynaptic current frequency, increased synaptic terminal density, and altered postsynaptic receptors. This increased synaptic drive together with altered cardiac neuron electrophysiology could increase intracardiac nervous system excitability and contribute to the substrate for atrial arrhythmia in hypertensive heart disease.

Diffuse or hitch a ride: how photoreceptor lipidated proteins get from here to there

Photoreceptors are polarized neurons, with specific subcellular compartmentalization and unique requirements for protein expression and trafficking. Each photoreceptor contains an outer segment (OS) where vision begins, an inner segment (IS) where protein synthesis occurs and a synaptic terminal for signal transmission to second-order neurons. The OS is a large, modified primary cilium attached to the IS by a slender connecting cilium (CC), the equivalent of the transition zone (TZ). Daily renewal of ~10% of the OS requires massive protein biosynthesis in the IS with reliable transport and targeting pathways. Transport of lipidated (‘sticky’) proteins depends on solubilization factors, phosphodiesterase δ (PDEδ) and uncoordinated protein-119 (UNC119), and the cargo dispensation factor (CDF), Arf-like protein 3-guanosine triphosphate (ARL3-GTP). As PDE6 and transducin still reside prominently in the OS of PDEδ and UNC119 germline knockout mice, respectively, we propose the existence of an alternate trafficking pathway, whereby lipidated proteins migrate in rhodopsin-containing vesicles of the secretory pathway.

The first one hundred nanometers inside the pre-synaptic terminal where calcium diffusion triggers vesicular release

Calcium diffusion in the thin one hundred nanometers layer located between the plasma membrane and docked vesicles in the pre-synaptic terminal of neuronal cells mediates vesicular fusion and synaptic transmission. Accounting for the narrow-cusp geometry located underneath the vesicle is a key ingredient that defines the probability and the time scale of calcium diffusion to bind calcium sensors for the initiation of vesicular release. We study here the time scale, the calcium binding dynamics and the consequences for asynchronous versus synchronous release. To conclude, threedimensional modeling approaches and the associated coarse-grained simulations can now account efficiently for the precise co-organization of vesicles and Voltage-Gated-Calcium-Channel (VGCC). This co-organization is a key determinant of short-term plasticity and it shapes asynchronous release. Moreover, changing the location of VGCC from few nanometers underneath the vesicle modifies significantly the release probability. Finally, by modifying the calcium buffer concentration, a single synapse can switch from facilitation to depression.