Voltage-sensitive dye imaging reveals tonotopic organization of auditory cortex spontaneous activity

Imaging neural activity across a large (several mm) cortical area with high temporal and spatial resolution is desirable, for example in the auditory system to measure cortical processing across a broad frequency spectrum. Voltage-sensitive dye imaging (VSDI) has a unique combination of properties making this possible, but so far studies have been limited to studying simple sparsely-presented sensory stimuli. We demonstrate the feasibility of long-acquisition VSDI (using the dye RH-1691) in auditory cortex while presenting complex time-varying acoustic stimuli or silence. Using a dense array of partially-overlapping 50 ms tone pips (8 frequencies per octave spanning six octaves), we obtained high-resolution spectrotemporal receptive fields (STRFs) simultaneously across the majority of the guinea pig primary auditory cortical fields (A1 and DC). Long epochs of spontaneous activity were also measured, permitting a comparison of spontaneous activity patterns with functional architecture. By grouping all pixels in areas A1 and DC according to sound frequency preference (obtained from STRFs), we reveal that spontaneous activity (such as cortical spindles) show complex spatial patterns, which are organized according to sound frequency preference within and across cortical areas. More specifically, spontaneous activity correlation decreases as frequency preference diverges within A1 or DC; but additionally, pixels in A1 are also highly correlated with (even far-away) pixels in DC sharing similar frequency preference. These properties of patterned cortical spontaneous activity constrain mechanistic hypotheses regarding their genesis. Beyond these observations, the feasibility of VSDI with continuous stimulation or silence permits measuring population activity during long-lasting sound patterns, which is necessary for examining cortical dynamics and sensory-context dependent processing

Principles underlying the development and organization of feature maps in the visual cortex

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, February 2007.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (leaves 139-142).A fundamental question in neuroscience is how sensory information is represented in the brain. In particular, what principles guide the spatial organization of neurons with regard to their receptive field properties, and how is this organization established mechanistically? The visual cortex serves as a model area to address these questions, but whether general principles can explain the layouts of cortical maps, such as those of visual space and of specific response features, remains unresolved. We find that in primary visual cortex of ferret, the layout of each map is inter-dependent with that of the others. First, we find a strong anisotropy in the visual map, such that receptive field positions change more rapidly along one axis of cortex; and importantly, along the axis where visual space changes rapidly, the feature maps of orientation, ocular dominance, and spatial frequency change slowly. Second, orientation, ocular dominance, and spatial frequency maps have local spatial relationships with each other: in areas of cortex where one feature changes rapidly, the other features change more slowly. Each of these relationships are well-explained by a dimension-reduction model of cortex.(cont.) This suggests that the constraints which drive map formation in the model, continuity (representing each feature smoothly across cortex) and coverage uniformity (representing each feature combination to an equal extent), may play a central role in determining the functional organization of visual cortex. To explore the mechanisms giving rise to the map relationships, we alter the expression of one feature map early in development and measure the impact on the layouts of the remaining maps. We find that alteration of the ocular dominance map, due to neonatal monocular enucleation, does not prevent the formation of the orientation and spatial frequency maps, but it does alter their spatial relationships. The highest gradient regions of the spatial frequency map have a stronger tendency to avoid high gradient orientation regions, and the contours of the two maps have a greater tendency to cross orthogonally. The results are consistent with the predictions of a dimension-reduction model for removing a feature map, suggesting that as a result of altered input patterns, the cortex can rearrange over the time scale of development according to a dimension-reduction strategy.by Brandon J. Farley.Ph.D

The Coordinated Mapping of Visual Space and Response Features in Visual Cortex

SummaryWhether general principles can explain the layouts of cortical maps remains unresolved. In primary visual cortex of ferret, the relationships between the maps of visual space and response features are predicted by a “dimension-reduction” model. The representation of visual space is anisotropic, with the elevation and azimuth axes having different magnification. This anisotropy is reflected in the orientation, ocular dominance, and spatial frequency domains, which are elongated such that their directions of rapid change, or high-gradient axes, are orthogonal to the high-gradient axis of the visual map. The feature maps are also strongly interdependent—their high-gradient regions avoid one another and intersect orthogonally where essential, so that overlap is minimized. Our results demonstrate a clear influence of the visual map on each feature map. In turn, the local representation of visual space is smooth, as predicted when many features are mapped within a cortical area

Conserved enhancers control notochord expression of vertebrate Brachyury.

The cell type-specific expression of key transcription factors is central to development and disease. Brachyury/T/TBXT is a major transcription factor for gastrulation, tailbud patterning, and notochord formation; however, how its expression is controlled in the mammalian notochord has remained elusive. Here, we identify the complement of notochord-specific enhancers in the mammalian Brachyury/T/TBXT gene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover three conserved Brachyury-controlling notochord enhancers, T3, C, and I, in human, mouse, and marsupial genomes. Acting as Brachyury-responsive, auto-regulatory shadow enhancers, in cis deletion of all three enhancers in mouse abolishes Brachyury/T/Tbxt expression selectively in the notochord, causing specific trunk and neural tube defects without gastrulation or tailbud defects. The three Brachyury-driving notochord enhancers are conserved beyond mammals in the brachyury/tbxtb loci of fishes, dating their origin to the last common ancestor of jawed vertebrates. Our data define the vertebrate enhancers for Brachyury/T/TBXTB notochord expression through an auto-regulatory mechanism that conveys robustness and adaptability as ancient basis for axis development

Thermal history of the central Gotthard and Aar massifs, European Alps: Evidence for steady state, long-term exhumation

International audienceQuantifying long-term exhumation rates is a prerequisite for understanding the geodynamic evolution of orogens and their exogenic and endogenic driving forces. Here we reconstruct the exhumation history of the central Aar and Gotthard external crystalline massifs in the European Alps using apatite and zircon fission track and apatite (U-Th)/He data. Age-elevation relationships and time-temperature paths derived from thermal history modeling are interpreted to reflect nearly constant exhumation of ∼0.5 km/Ma since ∼14 Ma. A slightly accelerated rate (∼0.7 km/Ma) occurred from 16 to 14 Ma and again from 10 to 7 Ma. Faster exhumation between 16 and 14 Ma is most likely linked to indentation of the Adriatic wedge and related thrusting along the Alpine sole thrust, which, in turn, caused uplift and exhumation in the external crystalline massifs. The data suggest nearly steady, moderate exhumation rates since ∼14 Ma, regardless of major exogenic and endogenic forces such as a change to wetter climate conditions around 5 Ma or orogen-perpendicular extension initiated in Pliocene times. Recent uplift and denudation rates, interpreted to be the result of climate fluctuations and associated increase in erosional efficiency, are nearly twice this ∼0.5 km/Ma paleoexhumation rate

RGS4 inhibits angiotensin II signaling and macrophage localization during renal reperfusion injury independent of vasospasm

Vascular inflammation is a major contributor to the severity of acute kidney injury. In the context of vasospasm-independent reperfusion injury we studied the potential anti-inflammatory role of the Gα-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 minute injury, although post-ischemic renal arteriolar diameter was equal to the wild type early after injury. A 10 minute unilateral injury was performed to study reperfusion without vasospasm. Eighteen hours after injury blood flow was decreased in the inner cortex of wild type mice with preservation of tubular architecture. Angiotensin II levels in the kidneys of wild type and transgenic mice were elevated in a sub-vasoconstrictive range 12 and 18 hours after injury. Angiotensin II stimulated pre-glomerular vascular smooth muscle cells (VSMC) to secrete the macrophage chemoattractant, RANTES; a process decreased by angiotensin II R2 (AT2) inhibition. However, RANTES increased when RGS4 expression was suppressed implicating Gα protein activation in an AT2-RGS4-dependent pathway. RGS4 function, specific to VSMC, was tested in a conditional VSMC-specific RGS4 knockout showing high macrophage density by T2 MRI compared to transgenic and non-transgenic mice after the 10 minute injury. Arteriolar diameter of this knockout was unchanged at successive time points after injury. Thus, RGS4 expression, specific to renal VSMC, inhibits angiotensin II-mediated cytokine signaling and macrophage recruitment during reperfusion, distinct from vasomotor regulation

Exhumation history along the eastern Amundsen Sea coast, West Antarctica, revealed by low-temperature thermochronology

West Antarctica experienced a complex tectonic history, which is still poorly documented, in part due to extensive ice cover. Here we reconstruct the Cretaceous to present thermotectonic history of Pine Island Bay area and its adjacent coasts, based on a combination of apatite and zircon fission track and apatite (U-Th-Sm)/He thermochronology. In addition, we report petrographic information for the catchments of Pine Island, Thurston Island, and Thwaites glaciers. Our data suggest that the underlying bedrock of the Pine Island and Thwaites Glacier catchments are very different and vary from granitoids to (Cenozoic?) volcanogenic sequences and low-grade metamorphics. Our thermochronology data show that the upper crustal rocks of Pine Island Bay experienced very rapid cooling during the late Cretaceous. We attribute this rapid cooling of basement rocks and associated reduction in mean elevation to tectonic denudation driven by gravitational collapse of the Cretaceous orogen along the proto-Pacific Gondwana margin. Rapid Cretaceous crustal cooling was followed by very slow cooling during the Cenozoic, with no erosional response—within the limits of thermochronological methods—to the onset of glaciation and subsequent climatic changes. Cenozoic rifting within the West Antarctic Rift appears to have had little effect on erosion processes around Pine Island Bay; instead, our data suggest Cenozoic crustal tilting toward Pine Island Trough, a major geomorphic feature previously suggested to be a branch of the rift system

Spatial correlation bias in late-Cenozoic erosion histories derived from thermochronology

International audienceThe potential link between erosion rates at the Earth's surface and changes in global climate has intrigued geoscientists for decades1,2 because such a coupling has implications for the influence of silicate weathering3,4 and organic-carbon burial5 on climate and for the role of Quaternary glaciations in landscape evolution1,6. A global increase in late-Cenozoic erosion rates in response to a cooling, more variable climate has been proposed on the basis of worldwide sedimentation rates7. Other studies have indicated, however, that global erosion rates may have remained steady, suggesting that the reported increases in sediment-accumulation rates are due to preservation biases, depositional hiatuses and varying measurement intervals8-10. More recently, a global compilation of thermochronology data has been used to infer a nearly twofold increase in the erosion rate in mountainous landscapes over late-Cenozoic times6. It has been contended that this result is free of the biases that affect sedimentary records11, although others have argued that it contains biases related to how thermochronological data are averaged12 and to erosion hiatuses in glaciated landscapes13. Here we investigate the 30 locations with reported accelerated erosion during the late Cenozoic6. Our analysis shows that in 23 of these locations, the reported increases are a result of a spatial correlation bias—that is, combining data with disparate exhumation histories, thereby converting spatial erosion-rate variations into temporal increases. In four locations, the increases can be explained by changes in tectonic boundary conditions. In three cases, climatically induced accelerations are recorded, driven by localized glacial valley incision. Our findings suggest that thermochronology data currently have insufficient resolution to assess whether late-Cenozoic climate change affected erosion rates on a global scale. We suggest that a synthesis of local findings that include location-specific information may help to further investigate drivers of global erosion rates

Effect of IBMX and alkaline phosphatase inhibitors on Cl- secretion in G551D cystic fibrosis mutant mice

Some cystic fibrosis transmembrane conductance regulator (CFTR) mutations, such as G551D, result in a correctly localized Cl channel at the cell apical membrane, albeit with markedly reduced function. Patch-clamp studies have indicated that both phosphatase inhibitors and 3-isobutyl-1- methylxanthine (IBMX) can induce Cl secretion through the G551D mutant protein. We have now assessed whether these agents can induce Cl secretion in cftr(G551D) mutant mice. No induction of Cl secretion was seen with the alkaline phosphatase inhibitors bromotetramisole or levamisole in either the respiratory or intestinal tracts of wild-type or cftr(G551D) mice. In contrast, in G551D intestinal tissues, IBMX was able to produce a small CFTR- related secretory response [means ± SE: jejunum, 1.8 ± 0.9 μA/cm, n = 7; cecum, 3.7 ± 0.8 μA/cm, n = 7; rectum (in vivo), 1.9 ± 0.9 mV, n = 5]. This was approximately one order of magnitude less than the wild-type response to this agent and, in the cecum, was significantly greater than that seen in null mice (cftr(UNC)). In the trachea, IBMX produced a transient Cl secretory response (37.3 ± 14.7 μA/cm, n = 6) of a magnitude similar to that seen in wild-type mice (33.7 ± 4.7 μA/cm, n = 9). This response was also present in null mice and therefore is likely to be independent of CFTR. No effect of IBMX on Cl secretion was seen in the nasal epithelium of cftr(G551D) mice. We conclude that IBMX is able to induce detectable levels of CFTR-related Cl secretion in the intestinal tract but not the respiratory tract through the G551D mutant protein