Faculty Bibliography

This article presents two related advancements to the diffusional kurtosis imaging estimation framework to increase its robustness to noise, motion, and imaging artifacts. The first advancement substantially improves the estimation of diffusion and kurtosis tensors parameterizing the diffusional kurtosis imaging model. Rather than utilizing conventional unconstrained least squares methods, the tensor estimation problem is formulated as linearly constrained linear least squares, where the constraints ensure physically and/or biologically plausible tensor estimates. The exact solution to the constrained problem is found via convex quadratic programming methods or, alternatively, an approximate solution is determined through a fast heuristic algorithm. The computationally more demanding quadratic programming-based method is more flexible, allowing for an arbitrary number of diffusion weightings and different gradient sets for each diffusion weighting. The heuristic algorithm is suitable for real-time settings such as on clinical scanners, where run time is crucial. The advantage offered by the proposed constrained algorithms is demonstrated using in vivo human brain images. The proposed constrained methods allow for shorter scan times and/or higher spatial resolution for a given fidelity of the diffusional kurtosis imaging parametric maps. The second advancement increases the efficiency and accuracy of the estimation of mean and radial kurtoses by applying exact closed-form formulae. Magn Reson Med, 2011. (c) 2010 Wiley-Liss, Inc

Fast-spiking (FS) cells are a prominent subtype of neocortical gamma-aminobutyric acidergic interneurons that mediate feed-forward inhibition and the temporal sculpting of information transfer in neural circuits, maintain excitation/inhibition balance, and contribute to network oscillations. FS cell dysfunction may be involved in the pathogenesis of disorders such as epilepsy, autism, and schizophrenia. Mature FS cells exhibit coordinated molecular and cellular specializations that facilitate rapid responsiveness, including brief spikes and sustained high-frequency discharge. We show that these features appear during the second and third postnatal weeks driven by upregulation of K(+) channel subunits of the Kv3 subfamily. The low membrane resistance and fast time constant characteristic of FS cells also appears during this time, driven by expression of a K(+) leak current mediated by K(ir)2 subfamily inward rectifier K(+) channels and TASK subfamily 2-pore K(+) channels. Blockade of this leak produces dramatic depolarization of FS cells suggesting the possibility for potent neuromodulation. Finally, the frequency of FS cell membrane potential oscillations increases during development and is markedly slower in TASK-1/3 knockout mice, suggesting that TASK channels regulate FS cell rhythmogenesis. Our findings imply that some of the effects of acidosis and/or anesthetics on brain function may be due to blockade of TASK channels in FS cells

Songs of many songbird species consist of variable sequences of a finite number of syllables. A common approach for characterizing the syntax of these complex syllable sequences is to use transition probabilities between the syllables. This is equivalent to the Markov model, in which each syllable is associated with one state, and the transition probabilities between the states do not depend on the state transition history. Here we analyze the song syntax in Bengalese finch. We show that the Markov model fails to capture the statistical properties of the syllable sequences. Instead, a state transition model that accurately describes the statistics of the syllable sequences includes adaptation of the self-transition probabilities when states are revisited consecutively, and allows associations of more than one state to a given syllable. Such a model does not increase the model complexity significantly. Mathematically, the model is a partially observable Markov model with adaptation (POMMA). The success of the POMMA supports the branching chain network model of how syntax is controlled within the premotor song nucleus HVC, but also suggests that adaptation and many-to-one mapping from the syllable-encoding chain networks in HVC to syllables should be included in the network model.

The fourth Leon Thal Symposium (LTS2010) was convened in Toulouse, France, on November 3, 2010. This symposium reviewed design parameters that are necessary to develop comprehensive national databases on healthy aging. Such datasets offer the potential to serve as the foundation for a systems-approach to solve the dual public health problems of: (1) early detection of people who are at elevated risk for Alzheimer's disease, and (2) the development of interventions to delay onset of, or prevent, late-life dementia. The symposium considered three interrelated components of a National Database for Longitudinal Studies on Healthy Aging as follows: (a) a registry of healthy aging adults; (b) refined computer-based assessments for data gathering, including assessments of behavioral/memory changes associated with aging that are appropriate for broad use in nonexpert settings; and (c) high performance computing/supercomputer-based approaches for health data modeling and mining

By studying the primary forebrain auditory area of songbirds, field L, using a song-inspired synthetic stimulus and reverse correlation techniques, we found a surprisingly systematic organization of this area, with nearly all neurons narrowly tuned along the spectral dimension, the temporal dimension, or both; there were virtually no strongly orientation-sensitive cells, and in the areas that we recorded, cells broadly tuned in both time and frequency were rare. In addition, cells responsive to fast temporal frequencies predominated only in the field L input layer, suggesting that neurons with fast and slow responses are concentrated in different regions. Together with other songbird data and work from chicks and mammals, these findings suggest that sampling a range of temporal and spectral modulations, rather than orientation in time-frequency space, is the organizing principle of forebrain auditory sensitivity. We then examined the role of these acoustic parameters important to field L organization in a behavioral task. Birds' categorization of songs fell off rapidly when songs were altered in frequency, but, despite the temporal sensitivity of field L neurons, the same birds generalized well to songs that were significantly changed in timing. These behavioral data point out that we cannot assume that animals use the information present in particular neurons without specifically testing perception.

Voltage-sensitive dye activity within the thin, unfoliated turtle cerebellar cortex (Cb) was recorded in vitro during eighth cranial nerve (nVIII) stimulation. Short latency responses were localized to the middle of the lateral edges of both ipsilateral and contralateral Cb [vestibulocerebellum (vCb)]. Even with a severed contralateral Cb peduncle, stimulation of the nVIII ipsilateral to the intact peduncle evoked contralateral vCb responses with a mean latency of only 0.25 ms after the ipsilateral responses, even though the distance between them was approximately 5 mm. We investigated whether a rapidly conducting commissure exists between each vCb by stimulating one of them directly. Responses in both vCb spread sagittally, but, surprisingly, there was no sequential activation along a transverse Cb beam between them. In contrast, stimulation medial to either vCb evoked transverse beams that required approximately 20 ms to cross the Cb. Therefore, the rapid commissural connection between each vCb is not mediated by slowly conducting parallel fibers. Also, the vCb was not strongly activated by climbing fiber stimulation, suggesting that inputs to vCb involve distinct cerebellar circuits. Responses between the two vCb remained following knife cuts through the rostral and caudal Cb along the midline, through both peduncles, and even shallow midline cuts to the middle Cb through its white matter and granule cell layer. Commissural responses were still observed only with a narrow transverse bridge between each vCb or in thick transverse Cb slices. Horseradish peroxidase transport from one vCb labeled transverse axons traveling within the Purkinje cell layer that were larger than parallel fibers and lacked varicosities. In sagittal sections, cross-section profiles of myelinated axons were observed around Purkinje cells midway between the rostral and caudal Cb. This novel pathway for transverse communication between lateral edges of turtle Cb suggests that afferents may directly conduct vestibular information rapidly across the Cb to coordinate vestibulomotor reflex behaviors

Crocipodin, an unusual benzotropolone pigment, has been isolated from the fruit bodies of the mushroom Leccinum crocipodium. Its structure was determined by spectroscopic methods, particularly 2D NMR spectroscopy. The structure was confirmed by total synthesis, starting from 4-bromocatechol and gallic acid. (C) 2010 Elsevier Ltd. All rights reserved.

Hippocampal neurons can display reliable and long-lasting sequences of transient firing patterns, even in the absence of changing external stimuli. We suggest that time-keeping is an important function of these sequences, and propose a network mechanism for their generation. We show that sequences of neuronal assemblies recorded from rat hippocampal CA1 pyramidal cells can reliably predict elapsed time (15-20 s) during wheel running with a precision of 0.5 s. In addition, we demonstrate the generation of multiple reliable, long-lasting sequences in a recurrent network model. These sequences are generated in the presence of noisy, unstructured inputs to the network, mimicking stationary sensory input. Identical initial conditions generate similar sequences, whereas different initial conditions give rise to distinct sequences. The key ingredients responsible for sequence generation in the model are threshold-adaptation and a Mexican-hat-like pattern of connectivity among pyramidal cells. This pattern may arise from recurrent systems such as the hippocampal CA3 region or the entorhinal cortex. We hypothesize that mechanisms that evolved for spatial navigation also support tracking of elapsed time in behaviorally relevant contexts

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.

Considerable evidence indicates that the general blockade of protein synthesis prevents both the initial consolidation and the postretrieval reconsolidation of long-term memories. These findings come largely from studies of drugs that block ribosomal function, so as to globally interfere with both cap-dependent and -independent forms of translation. Here we show that intra-amygdala microinfusions of 4EGI-1, a small molecule inhibitor of cap-dependent translation that selectively disrupts the interaction between eukaryotic initiation factors (eIF) 4E and 4G, attenuates fear memory consolidation but not reconsolidation. Using a combination of behavioral and biochemical techniques, we provide both in vitro and in vivo evidence that the eIF4E-eIF4G complex is more stringently required for plasticity induced by initial learning than for that triggered by reactivation of an existing memory