Faculty Bibliography

Eusocial insects organize themselves into behavioral castes whose regulation has been proposed to involve epigenetic processes, including histone modification. In the carpenter ant Camponotus floridanus, morphologically distinct worker castes called minors and majors exhibit pronounced differences in foraging and scouting behaviors. We found that these behaviors are regulated by histone acetylation likely catalyzed by the conserved acetyltransferase CBP. Transcriptome and chromatin analysis in brains of scouting minors fed pharmacological inhibitors of CBP and histone deacetylases (HDACs) revealed hundreds of genes linked to hyperacetylated regions targeted by CBP. Majors rarely forage, but injection of a HDAC inhibitor or small interfering RNAs against the HDAC Rpd3 into young major brains induced and sustained foraging in a CBP-dependent manner. Our results suggest that behavioral plasticity in animals may be regulated in an epigenetic manner via histone modification.

Non-invasive fluorescence retinal imaging in small animals is an important requirement for an array of translational vision applications. The in vivo two-photon imaging of the mouse retina may enable the long-term investigation of the structure and function of healthy and diseased retinal tissue. However, to date, this has only been possible using relatively complex adaptive-optics systems. Here, the optical modeling of the murine eye and of the imaging system is used to achieve correction-free two-photon microscopy through the pupil of a mouse eye to yield high-quality, optically sectioned fundus images. By remotely scanning the focus using an electronically tunable lens, high-resolution three-dimensional fluorescein angiograms and cellular-scale images are acquired, thus introducing a correction-free baseline performance level for two-photon in vivo retinal imaging. Moreover, the system enables functional calcium imaging of repeated retinal responses to light stimulation using the genetically encoded indicator, GCaMP6s. These results and the simplicity of the new add-on optics are an important step toward several structural, functional, and multimodal imaging applications that will benefit from the tight optical sectioning and the use of near-infrared light.

Even though speech signals trigger coding in the cochlea to convey speech information to the central auditory structures, little is known about the neural mechanisms involved in such processes. The purpose of this study was to understand the encoding of formant cues and how it relates to vowel recognition in listeners. Neural representations of formants may differ across listeners; however, it was hypothesized that neural patterns could still predict vowel recognition. To test the hypothesis, the frequency-following response (FFR) and vowel recognition were obtained from 38 normal-hearing listeners using four different vowels, allowing direct comparisons between behavioral and neural data in the same individuals. FFR was employed because it provides an objective and physiological measure of neural activity that can reflect formant encoding. A mathematical model was used to describe vowel confusion patterns based on the neural responses to vowel formant cues. The major findings were (1) there were large variations in the accuracy of vowel formant encoding across listeners as indexed by the FFR, (2) these variations were systematically related to vowel recognition performance, and (3) the mathematical model of vowel identification was successful in predicting good vs poor vowel identification performers based exclusively on physiological data.

Stimulus-triggered protein synthesis is critical for brain health and function. However, due to technical hurdles, de novo neuronal translation is predominantly studied in cultured cells, whereas electrophysiological and circuit analyses often are performed in brain slices. The different properties of these two experimental systems create an information gap about stimulus-induced alterations in the expression of new proteins in mature circuits. To address this, we adapted two existing techniques, BONCAT and SILAC, to a combined proteomic technique, BONLAC, for use in acute adult hippocampal slices. Using BDNF-induced protein synthesis as a proof of concept, we found alterations in expression of proteins involved in neurotransmission, trafficking, and cation binding that differed from those found in a similar screen in cultured neurons. Our results indicate important differences between cultured neurons and slices, and suggest that BONLAC could be used to dissect proteomic changes underlying synaptic events in adult circuits.

Myocardial injuries often lead to fibrotic deposition. This review presents evidence supporting the concept that fibroblasts in the heart electrically couple to myocytes.

BACKGROUND: To evaluate the influence of temporal sparsity regularization and radial undersampling on compressed sensing reconstruction of dynamic contrast-enhanced (DCE) MRI, using the iterative Golden-angle RAdial Sparse Parallel (iGRASP) MRI technique in the setting of breast cancer evaluation. METHODS: DCE-MRI examinations of the breast (n = 7) were conducted using iGRASP at 3 Tesla. Images were reconstructed with five different radial undersampling schemes corresponding to temporal resolutions between 2 and 13.4 s/frame and with four different weights for temporal sparsity regularization (lambda = 0.1, 0.5, 2, and 6 times of noise level). Image similarity to time-averaged reference images was assessed by two breast radiologists and using quantitative metrics. Temporal similarity was measured in terms of wash-in slope and contrast kinetic model parameters. RESULTS: iGRASP images reconstructed with lambda = 2 and 5.1 s/frame had significantly (P < 0.05) higher similarity to time-averaged reference images than the images with other reconstruction parameters (mutual information (MI) >5%), in agreement with the assessment of two breast radiologists. Higher undersampling (temporal resolution < 5.1 s/frame) required stronger temporal sparsity regularization (lambda >/= 2) to remove streaking aliasing artifacts (MI > 23% between lambda = 2 and 0.5). The difference between the kinetic-model transfer rates of benign and malignant groups decreased as temporal resolution decreased (82% between 2 and 13.4 s/frame). CONCLUSION: This study demonstrates objective spatial and temporal similarity measures can be used to assess the influence of sparsity constraint and undersampling in compressed sensing DCE-MRI and also shows that the iGRASP method provides the flexibility of optimizing these reconstruction parameters in the postprocessing stage using the same acquired data. J. Magn. Reson. Imaging 2015.

KATP channels are integral to the functions of many cells and tissues. The use of electrophysiological methods has allowed for a detailed characterization of KATP channels in terms of their biophysical properties, nucleotide sensitivities, and modification by pharmacological compounds. However, even though they were first described almost 25 years ago (Noma 1983, Trube and Hescheler 1984), the physiological and pathophysiological roles of these channels, and their regulation by complex biological systems, are only now emerging for many tissues. Even in tissues where their roles have been best defined, there are still many unanswered questions. This review aims to summarize the properties, molecular composition, and pharmacology of KATP channels in various cardiovascular components (atria, specialized conduction system, ventricles, smooth muscle, endothelium, and mitochondria). We will summarize the lessons learned from available genetic mouse models and address the known roles of KATP channels in cardiovascular pathologies and how genetic variation in KATP channel genes contribute to human disease.

Increasing evidence over the past decade suggests that vision is not simply a passive, feed-forward process in which cortical areas relay progressively more abstract information to those higher up in the visual hierarchy, but rather an inferential process with top-down processes actively guiding and shaping perception. However, one major question that persists is whether such processes can be influenced by unconsciously perceived stimuli. Recent psychophysics and neuroimaging studies have revealed that while consciously perceived stimuli elicit stronger responses in higher visual and frontoparietal areas than those that fail to reach conscious awareness, the latter can still drive high-level brain and behavioral responses. We investigated whether unconscious processing of a masked natural image could facilitate subsequent conscious recognition of its degraded counterpart (a black-and-white "Mooney" image) presented many seconds later. We found that this is indeed the case, suggesting that conscious vision may be influenced by priors established by unconscious processing of a fleeting image.

PURPOSE: We investigated global specific absorption rate (SAR) and radiofrequency (RF) power requirements in parallel transmission as the distance between the transmit coils and the sample was increased. METHODS: We calculated ultimate intrinsic SAR (UISAR), which depends on object geometry and electrical properties but not on coil design, and we used it as the reference to compare the performance of various transmit arrays. We investigated the case of fixing coil size and increasing the number of coils while moving the array away from the sample, as well as the case of fixing coil number and scaling coil dimensions. We also investigated RF power requirements as a function of lift-off, and tracked local SAR distributions associated with global SAR optima. RESULTS: In all cases, the target excitation profile was achieved and global SAR (as well as associated maximum local SAR) decreased with lift-off, approaching UISAR, which was constant for all lift-offs. We observed a lift-off value that optimizes the balance between global SAR and power losses in coil conductors. We showed that, using parallel transmission, global SAR can decrease at ultra high fields for finite arrays with a sufficient number of transmit elements. CONCLUSION: For parallel transmission, the distance between coils and object can be optimized to reduce SAR and minimize RF power requirements associated with homogeneous excitation. Magn Reson Med, 2015. (c) 2015 Wiley Periodicals, Inc.