Faculty Bibliography

Efficient coding provides a powerful principle for explaining early sensory coding. Most attempts to test this principle have been limited to linear, noiseless models, and when applied to natural images, have yielded oriented filters consistent with responses in primary visual cortex. Here we show that an efficient coding model that incorporates biologically realistic ingredients - input and output noise, nonlinear response functions, and a metabolic cost on the firing rate - predicts receptive fields and response nonlinearities similar to those observed in the retina. Specifically, we develop numerical methods for simultaneously learning the linear filters and response nonlinearities of a population of model neurons, so as to maximize information transmission subject to metabolic costs. When applied to an ensemble of natural images, the method yields filters that are center-surround and nonlinearities that are rectifying. The filters are organized into two populations, with On- and Off-centers, which independently tile the visual space. As observed in the primate retina, the Off-center neurons are more numerous and have filters with smaller spatial extent. In the absence of noise, our method reduces to a generalized version of independent components analysis, with an adapted nonlinear "contrast" function; in this case, the optimal filters are localized and oriented.

The objective of this study was to evaluate the ability of a collagen membrane (CM) as a carrier to successfully deliver platelet-derived growth factor (PDGF) and to observe the subsequent effects of the factor on preosteoblasts in vitro. MC3T3-E1 mouse preosteoblasts were cultured with a commercially available CM containing PDGF. After a two-day cell culture, cell viability was investigated by the MTT assay and cell proliferation was assessed by the crystal violet proliferation assay. Expression levels of the following osteoblastic differentiation marker genes were measured by real-time PCR: runt-related transcription factor 2 (RUNX2), osteopontin (OPN), bone sialoprotein (BSP), and osteocalcin (OCN). A cell proliferation assay was conducted, and osteoblastogenesis was determined by alkaline phosphatase (ALP) activity. A sustained release of PDGF from a CM was observed for ~3 weeks. Gene expression of all RUNX2, OPN, BSP, and OCN in CM with PDGF was significantly upregulated compared to those in CM without PDGF (all p < 0.05). Interestingly, CM without PDGF also significantly increased gene expression of RUNX2 and OPN in MC3T3-E1 cells compared to the cell control (both p < 0.05). Furthermore, it was observed that the PDGF released from CM significantly promoted ALP activity and cell proliferation with little cytotoxicity. These results suggest that a CM can be utilized for sustained delivery of PDGF. Also, released PDGF can promote MC3T3-E1 cell activities. This strategy may lead to an improvement in the current clinical treatment of bone defects in periodontal and implant therapy

It has been shown recently that a significant portion of brain electrical field potentials consists of scale-free dynamics. These scale-free brain dynamics contain complex spatiotemporal structures and are modulated by task performance. Here we show that the fMRI signal recorded from the human brain is also scale free; its power-law exponent differentiates between brain networks and correlates with fMRI signal variance and brain glucose metabolism. Importantly, in parallel to brain electrical field potentials, the variance and power-law exponent of the fMRI signal decrease during task activation, suggesting that the signal contains more long-range memory during rest and conversely is more efficient at online information processing during task. Remarkably, similar changes also occurred in task-deactivated brain regions, revealing the presence of an optimal dynamic range in the fMRI signal. The scale-free properties of the fMRI signal and brain electrical field potentials bespeak their respective stationarity and nonstationarity. This suggests that neurovascular coupling mechanism is likely to contain a transformation from nonstationarity to stationarity. In summary, our results demonstrate the functional relevance of scale-free properties of the fMRI signal and impose constraints on future models of neurovascular coupling.

In a longitudinal study of recovery of left neglect following stroke using reaction time computerized assessment, we find that lateralized spatial deficits of attention and perception to be more severe than disturbance of action. Perceptual-attention deficits also show the most variability in the course of recovery, making them prime candidates for intervention. In an anatomical analysis of MRI findings, ventral frontal cortex damage was correlated with the most severe neglect, reflecting impaired fronto-parietal communication.

The purpose of this study was to develop a unified model capable of explaining the mechanisms of interaction of ultrasound and biological tissue at both the diagnostic nonthermal, noncavitational (<100 mW . cm(-2)) and therapeutic, potentially cavitational (>100 mW . cm(-2)) spatial peak temporal average intensity levels. The cellular-level model (termed "bilayer sonophore") combines the physics of bubble dynamics with cell biomechanics to determine the dynamic behavior of the two lipid bilayer membrane leaflets. The existence of such a unified model could potentially pave the way to a number of controlled ultrasound-assisted applications, including CNS modulation and blood-brain barrier permeabilization. The model predicts that the cellular membrane is intrinsically capable of absorbing mechanical energy from the ultrasound field and transforming it into expansions and contractions of the intramembrane space. It further predicts that the maximum area strain is proportional to the acoustic pressure amplitude and inversely proportional to the square root of the frequency (epsilon A,max proportional, variant P(A)(0.8f - 0.5) and is intensified by proximity to free surfaces, the presence of nearby microbubbles in free medium, and the flexibility of the surrounding tissue. Model predictions were experimentally supported using transmission electron microscopy (TEM) of multilayered live-cell goldfish epidermis exposed in vivo to continuous wave (CW) ultrasound at cavitational (1 MHz) and noncavitational (3 MHz) conditions. Our results support the hypothesis that ultrasonically induced bilayer membrane motion, which does not require preexistence of air voids in the tissue, may account for a variety of bioeffects and could elucidate mechanisms of ultrasound interaction with biological tissue that are currently not fully understood.

Temporal focusing is a simple approach for achieving tight, optically sectioned excitation in nonlinear microscopy and multiphoton photo-manipulation. Key applications and advantages of temporal focusing involve propagation through scattering media, but the progressive broadening of the temporal focus has not been characterized. By combining a detailed geometrical optics model with Monte-Carlo scattering simulations we introduce and validate a simulation strategy for predicting temporal focusing characteristics in scattering and non-scattering media. The broadening of the temporal focus width with increasing depth in brain tissue is studied using both simulations and experiments for several key optical geometries, and an analytical approximation is found for the dependence of this broadening on the microscope's parameters in a transparent medium. Our results indicate that a multiphoton temporal focus has radically different broadening characteristics in deep tissue than those of a spatial focus.

Holographic speckle is a major impediment for the emerging applications of multiphoton holographic projection in biomedical imaging, photo-stimulation and micromachining. Time averaging of multiple shifted versions of a single hologram ("shift-averaging") is a computationally-efficient method that was recently shown to deterministically eliminate holographic speckle in single-photon applications. Here, we extend these results and show, computationally and experimentally, that in two-photon holographic excitation shift-averaging also reduces holographic speckle better than "random" averaging of multiple calculated holograms.

The establishment of the germline is a critical, yet surprisingly evolutionarily labile, event in the development of sexually reproducing animals. In the fly Drosophila, germ cells acquire their fate early during development through the inheritance of the germ plasm, a specialized maternal cytoplasm localized at the posterior pole of the oocyte. The gene oskar (osk) is both necessary and sufficient for assembling this substance. Both maternal germ plasm and oskar are evolutionary novelties within the insects, as the germline is specified by zygotic induction in basally branching insects, and osk has until now only been detected in dipterans. In order to understand the origin of these evolutionary novelties, we used comparative genomics, parental RNAi, and gene expression analyses in multiple insect species. We have found that the origin of osk and its role in specifying the germline coincided with the innovation of maternal germ plasm and pole cells at the base of the holometabolous insects and that losses of osk are correlated with changes in germline determination strategies within the Holometabola. Our results indicate that the invention of the novel gene osk was a key innovation that allowed the transition from the ancestral late zygotic mode of germline induction to a maternally controlled establishment of the germline found in many holometabolous insect species. We propose that the ancestral role of osk was to connect an upstream network ancestrally involved in mRNA localization and translational control to a downstream regulatory network ancestrally involved in executing the germ cell program.

Color vision is found in many invertebrate and vertebrate species. It is the ability to discriminate objects based on the wavelength of emitted light independent of intensity. As it requires the comparison of at least two photoreceptor types with different spectral sensitivities, this process is often mediated by a mosaic made of several photoreceptor types. In this review, we summarize the current knowledge about the formation of retinal mosaics and the regulation of photopigment (opsin) expression in the fly, mouse, and human retina. Despite distinct evolutionary origins, as well as major differences in morphology and phototransduction machineries, there are significant similarities in the stepwise cell-fate decisions that lead from progenitor cells to terminally differentiated photoreceptors that express a particular opsin. Common themes include (i) the use of binary transcriptional switches that distinguish classes of photoreceptors, (ii) the use of gradients of signaling molecules for regional specializations, (iii) stochastic choices that pattern the retina, and (iv) the use of permissive factors with multiple roles in different photoreceptor types.

The development of two-component expression systems in Drosophila melanogaster, one of the most powerful genetic models, has allowed the precise manipulation of gene function in specific cell populations. These expression systems, in combination with site-specific recombination approaches, have also led to the development of new methods for clonal lineage analysis. We present a hands-on user guide to the techniques and approaches that have greatly increased resolution of genetic analysis in the fly, with a special focus on their application for lineage analysis. Our intention is to provide guidance and suggestions regarding which genetic tools are most suitable for addressing different developmental questions.