Dissecting the intrastriatal neuronal circuitry that regulates direct and indirect striatal projections

The basal ganglia (BG) are a group of subcortical nuclei that are interconnected in multiple parallel cortico-BG-thalamocortical loops. They have been implicated in many functions, among them action control and motor learning. The striatum forms the main input nucleus of the BG. Its principal neuron type, the medium spiny neuron (MSN), projects via striatonigral (direct) and striatopallidal (indirect) BG pathways, which according to an influential model function antagonistically in motor control. D1 and D2 receptor expressing MSNs ascribed to direct and indirect pathways, respectively, are not easily discriminable based on electrophysiological properties, but are hypothesized to be oppositely affected by dopamine (DA). A small population of striatal neurons, the fast-spiking interneurons (FSNs) however show characteristic stuttering discharge in vitro, and have an important role in mediating feedforward inhibition onto MSNs (which are also interconnected via feedback collaterals). FSNs form electrical, as well as chemical synapses onto each other. The focus of this thesis has been to investigate the characteristic electrical properties of the mentioned striatal neuron types and their dynamic interconnectivity, as well as DAergic modulation of MSNs of the different projection systems. In two animal models (rat and mouse), electrical properties of different MSN subtypes were similar, however, membrane excitability consistently differed with direct pathway MSNs being less excitable than their counterparts. DA had opposite effects on excitability of D1 and D2 MSNs, counteracting these initial differences. Excitability increased in D1 MSNs, across experimental conditions and parameters, and also when applying DA or D1 agonist during blockade of cholinergic, GABAergic, and glutamatergic synaptic transmission. FSNs provided a strong and homogeneously depressing “feedforward” inhibition of both striatonigral and striatopallidal MSNs, as measured with multineuron patch-clamp recordings in the acute slice. Individual FSNs were connected to MSNs of both types. In contrast, both MSN types received sparse and variable, depressing and facilitating synaptic “feedback” transmission from other MSNs. Connection probability appeared higher for pairs with presynaptic striatopallidal MSNs; however, the type of interconnected MSNs did not determine the variability in synaptic dynamics. The differences between feedback and feedforward inhibitory pathways were clear in two species at different developmental stages. Measurements in vitro and a computational FSN-model showed that FSNs that exhibit typical random stuttering discharge in response to steady depolarization do not show stuttering when they receive fluctuating input. The model predicts that electrically coupled FSNs show substantial spike synchronization only when in the stuttering regime. In vivo variability in FSN discharge was furthermore translated to high variability in postsynaptic amplitudes due to strong depression of the FS-MSN synapse. Using PV-Cre mice injected with AAV virus containing ChR2 and mCherry, we selectively photostimulated FSNs. When recording from nearby MSNs, FS, low-threshold spiking (LTS), and cholinergic (ACh) interneurons while activating FSNs, most MSNs received strong and reliable synaptic input, which was mediated by GABAa receptors, whereas ACh (and LTS) interneurons received no input at all. In conclusion, DA induced changes in excitability of identified MSNs were consistent with an influential model of BG function, and direct pathway excitability increases were mediated by D1 receptors most probably acting on intrinsic MSN properties. Synaptic dynamics generally differed between striatal feedforward versus feedback synapses, but were similar for both output pathways. Modeling suggested that in vivo, neighboring FSNs are not readily in the stuttering regime simultaneously, discharge variability is rather determined by input fluctuations, and synaptic dynamics lead to highly variable postsynaptic response amplitudes in MSNs. Feed-forward inhibition mediated by FSNs is highly target selective for MSNs in contrast to other interneuron types, especially ACh interneurons

Morphological structures relate to the location and extent of the seismogenic zone - bathymetric studies of the Sunda margin, Indonesia

Earthquake history shows that the Sunda subduction zone of the Indonesian margin produces great earthquakes offshore Sumatra, whereas earthquakes of comparable magnitude are lacking offshore Java and the Lesser Sunda islands. Morphological structures from multibeam bathymetric data across the forearc relate with the extent of the seismogenic zone (SZ). Off Java and the Lesser Sunda islands the Indo-Australian plate subducts almost normal underneath the oceanic plate of the Indonesian archipelago. Landward of the trench, the outer wedge of the slope break is ~50 km uniformly wide with uniform bathymetric gradients. The slope of the outer wedge is locally cut by one/two steeper ridges of ~5 km extent. The sharp slope break corresponds to the updip limit of the SZ, which is also associated with the seawardmost part of the outer arc high. Landward of the slope break we find narrow, uniform outer arc ridges. The landward termination of these ridges coincides with the downdip limit of the SZ. The intersection of the shallow upper plate mantle with the subduction thrust fault marks the downdip limit of the SZ beneath the forearc. Off Sumatra the Indo-Australian plate subducts obliquely underneath the continental part of the Indonesian Sunda margin. Landward of the trench, the outer wedge varies, being mostly ~70 km wide, in some areas narrowing to 50 km width. The lower slope bathymetric gradients are steep. The outer wedge slope is made up of several steeper ridges of ~5 km extent. The slope break is only locally sharp, and corresponds to the updip limit of the SZ. The outer arc ridges off Sumatra are, in comparison with the forearc structures off Java and the Lesser Sunda islands, wider and partly elevated above sea level forming the Mentawai forearc islands. The downdip limit of the SZ coincides with the intersection of a deeper upper plate mantle with the subduction thrust fault beneath the forearc. Sunda Strait marks a transition zone between the Sumatra and Java margins. Seafloor morphology enables the identification of the seismogenic zone (SZ) across the entire Sunda margin. The SZ is uniformly wide for the Sumatra margin and narrows off Sunda Strait. Sunda Strait is the transition between the Sumatra margin and the uniformly narrow extent of the SZ of the Java/Lesser Sunda margin. Comparing the Java and Lesser Sunda islands with the Sumatra margin we find the differences along the Sunda margin, especially the wider extent of the SZ off Sumatra, producing larger earthquakes, to result from the combination of various causes: The sediment income on the oceanic incoming plate and the subduction direction; we attribute a major role to the continental/oceanic upper plate nature of Sumatra/Java influencing the composition and deformation style along the forearc and subduction fault. Off Sumatra the SZ is up to more than twice as wide as off Java/Lesser Sunda islands, enlarging the unstable regime off Sumatra and thus the risk of sudden stress release in a great earthquake

Along- and across-axis variations in crustal thickness and structure at the Mid-Atlantic Ridge at 5°S obtained from wide-angle seismic tomography: implications for ridge segmentation

Two end‐member styles of crustal accretion are observed at two adjacent spreading segments at the Mid‐Atlantic Ridge at 5°S: focused accretion to the segment center with rapid crustal thinning toward the transform in the northern segment and crustal thickening toward the transform at an oceanic core complex in the southern segment. Our results were obtained by tomographic inversion of wide‐angle seismic reflection and refraction data collected along three intersecting profiles. The segment north of the 5°S fracture zone is characterized by a well‐developed median valley with a pronounced seafloor bulge in the segment center. A discrete portion of anomalously low velocities (−0.4 to −0.5 km/s relative to average off‐axis structure) at depths of ∼2.5 km beneath this bulge is possibly related to the presence of elevated temperatures and perhaps small portions of partial melt. This suggests that this segment is currently in a magmatically active period, which is confirmed by the observation of fresh lava flows and ongoing high‐temperature hydrothermal activity at the seafloor. Close to the current spreading axis, the crust thins rapidly from 8.5 km beneath the segment center to less than 3 km beneath the transform fault which indicates that melt supply here is strongly focused to the segment center. The reduction in crustal thickness is almost exclusively accommodated by the thinning of velocity portions indicative of seismic layer 3. The transform fault is characterized by more uniform velocity gradients throughout the entire crustal section and very low upper mantle velocities of 7.2–7.3 km/s indicating that serpentinization could be as much as 25% at 3.5 km depth. In contrast, ∼4.1 Ma old crust of the northern segment shows only minor thinning from the segment center toward the segment end. Here, the transform is characterized by a normal seismic layer 2/3 transition suggesting robust melt supply to the segment end at those times. In the adjacent southern segment, the crust thickens from ∼2.5 km beneath the flank of an oceanic core complex to ∼5.0 km at the segment boundary. The observed changes in crustal thickness show a significant temporal and lateral variability in melt supply and suggest a more complex crustal emplacement process than predicted by models of focused melt supply to the segment centers

Margin architecture and seismic attenuation in the central Costa Rican forearc

Seismic attenuation across the central Costa Rican margin wedge is determined fromamplitude analysis ofwideangle seismic data. Travel time and amplitude modeling are applied to ocean bottom hydrophones along two trench-parallel profiles, located 30 km (P21) and 35 km (P18) landward of the deformation front northeast of Quepos Plateau. Tomographic inversion images a progressively thinning margin wedge from the coast to the lower slope at the trench. A 1–1.5 km thick décollement zone with seismic velocities of 3.5–4.5 km/s is sandwiched between the marginwedge and the subducting Cocos plate. For strike line P21, amplitude modeling indicates a Qp value of 50–150 for the upper margin wedge with seismic velocities ranging from 3.9 km/s to 4.9 km/s. Along strike line P18, Qp values of 50–150 are determined with velocities of 4.3–5.0 km/s in the upper margin wedge, increasing to 5.1–5.4 km/s in the lower margin wedge. Quantitative amplitude decay curves support the observed upper plate Qp values. In conjunction with earlier results from offshore Nicoya Peninsula, our study documents landward decreasing attenuation across the margin wedge, consistent with a change in lithology from the sediment-dominated frontal prism to the igneous composition of the forearc middle pris