Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neuroscience Institute
Total Results:
13474
Re-evaluation of post-wash sperm is a helpful tool in the decision to perform in vitro fertilisation or intracytoplasmic sperm injection
The aim of this study was to find discriminatory parameters, based on sperm characteristics on the day of ovum pickup, that can help guide the decision to perform either intracytoplasmic sperm injection (ICSI) or in vitro fertilisation (IVF). We evaluated 112 cycles fertilised with both regular and ICSI insemination during the same cycle. A total of 112 cycles were analysed. In 62 cycles, fertilisation was obtained with both ICSI and IVF, and in 50 cycles, fertilisation was obtained by ICSI alone. The sperm samples were re-evaluated after the preparation process. The mean initial total motile sperm count (TMSC) was 66.3 x 10(6) +/- 47.5 in the group that underwent both methods and 23.1 x 10(6) +/- 20.4 in the ICSI only group (P < 0.05). After sperm preparation, the mean post-wash TMSC was 4.4 x 10(6) +/- 3.4 and 1.06 x 10(6) +/- 0.9 respectively (P < 0.05). A cutoff of 1.5 x 10(6) or fewer sperm after preparation as an indicator for ICSI has a sensitivity of 80% and a specificity of 77%. Re-evaluation of TMSC can prevent unexpected fertilisation failure. Fewer than 1.5 million TMSC after wash should be considered an indication for ICSI fertilisation.
PMID: 21714800
ISSN: 0303-4569
CID: 231482
Whole body traveling wave magnetic resonance imaging at high field strength: Homogeneity, efficiency, and energy deposition as compared with traditional excitation mechanisms
In 7 T traveling wave imaging, waveguide modes supported by the scanner radiofrequency shield are used to excite an MR signal in samples or tissue which may be several meters away from the antenna used to drive radiofrequency power into the system. To explore the potential merits of traveling wave excitation for whole-body imaging at 7 T, we compare numerical simulations of traveling wave and TEM systems, and juxtapose full-wave electrodynamic simulations using a human body model with in vivo human traveling wave imaging at multiple stations covering the entire body. The simulated and in vivo traveling wave results correspond well, with strong signal at the periphery of the body and weak signal deep in the torso. These numerical results also illustrate the complicated wave behavior that emerges when a body is present. The TEM resonator simulation allowed comparison of traveling wave excitation with standard quadrature excitation, showing that while the traveling wave B +1 per unit drive voltage is much less than that of the TEM system, the square of the average B +1 compared to peak specific absorption rate (SAR) values can be comparable in certain imaging planes. Both systems produce highly inhomogeneous excitation of MR signal in the torso, suggesting that B(1) shimming or other parallel transmission methods are necessary for 7 T whole body imaging. Magn Reson Med 67:1183-1193, 2011. (c) 2011 Wiley-Liss, Inc.
PMCID:3376911
PMID: 21842501
ISSN: 0740-3194
CID: 162021
Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo
More than 30 neurodegenerative diseases including Alzheimer disease (AD), frontotemporal lobe dementia (FTD), and some forms of Parkinson disease (PD) are characterized by the accumulation of an aggregated form of the microtubule-binding protein tau in neurites and as intracellular lesions called neurofibrillary tangles. Diseases with abnormal tau as part of the pathology are collectively known as the tauopathies. Methylthioninium chloride, also known as methylene blue (MB), has been shown to reduce tau levels in vitro and in vivo and several different mechanisms of action have been proposed. Herein we demonstrate that autophagy is a novel mechanism by which MB can reduce tau levels. Incubation with nanomolar concentrations of MB was sufficient to significantly reduce levels of tau both in organotypic brain slice cultures from a mouse model of FTD, and in cell models. Concomitantly, MB treatment altered the levels of LC3-II, cathepsin D, BECN1, and p62 suggesting that it was a potent inducer of autophagy. Further analysis of the signaling pathways induced by MB suggested a mode of action similar to rapamycin. Results were recapitulated in a transgenic mouse model of tauopathy administered MB orally at three different doses for two weeks. These data support the use of this drug as a therapeutic agent in neurodegenerative diseases.
PMCID:3405840
PMID: 22361619
ISSN: 1554-8635
CID: 2077002
Physical review. E. Statistical, nonlinear, & soft matter physics. 2012:85(4 Pt 1).DOI: 10.1103/PhysRevE.85.041905
Tunable oscillations in the Purkinje neuron
In this paper, we experimentally study the dynamics of slow oscillations in Purkinje neurons in vitro, and derive a strong association with a forced parametric oscillator model. We observed the precise rhythmicity of these oscillations in Purkinje neurons, as well as a dynamic tunability of this oscillation using a photoswitchable compound. We found that this slow oscillation can be induced in every Purkinje neuron measured, having periods ranging between 10 and 25 s. Starting from a Hodgkin-Huxley model, we demonstrate that this oscillation can be externally modulated, and that the neurons will return to their intrinsic firing frequency after the forced oscillation is concluded. These findings signify an additional timing functional role of tunable oscillations within the cerebellum, as well as a dynamic control of a time scale in the brain in the range of seconds.
PMID: 22680496
ISSN: 1550-2376
CID: 2484972
Guidelines for the use and interpretation of assays for monitoring autophagy [Guideline]
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
PMCID:3404883
PMID: 22966490
ISSN: 1554-8627
CID: 181862
Behavioral and physiological measure for pitch matching between electrical and acoustical stimulation in cochlear implant patients
This study examines behavioral and physiological measures of pitch matching in cochlear implant (CI) users who have residual hearing in the contralateral ear. Subjects adjusted the frequency of an acoustic tone to match the pitch percept elicited by electrical stimulation in the other ear, when stimulation was alternating across two ears. In general, the selected acoustic frequencies did not line up perfectly with the center frequencies of the analysis bands corresponding to each stimulation electrode. Similar alternating electro-acoustic stimuli were used to record Auditory Evoked Potentials on 8 NH subjects and 3 CI patients. NH subjects were presented with a fixed tone in one ear, while tones in the other ear varied within a few octaves from the fixed tone. CI patients were stimulated with six different audible tones including their pitch-matched tones, while receiving electrical stimulation in the electrode. N1 latency for NH subjects was minimized when the same frequency was presented to both ears. Similarly, N1 latency for CI patients who are able to pitch match was minimized when the tone was at the pitch matched frequency of the stimulated electrode. These results suggest that N1 latency can be a possible objective measure of pitch matching. (Work supported by NIH/NIDCD 1K25DC010834-01;PI:Tan, PSC-CUNY;PI:Martin, and NIH/NIDCD R01-DC03937;PI:Svirsky.).
ORIGINAL:0010418
ISSN: 0001-4966
CID: 1899612
Extracellular diffusion in laminar brain structures exemplified by hippocampus
Numerous brain structures are composed of distinct layers and such stratification has a profound effect on extracellular diffusion transport in these structures. We have derived a more general form of diffusion equation incorporating inhomogeneities in both the extracellular volume fraction (alpha) and diffusion permeability (theta). A numerical solution of this equation for a special case of layered environment was employed to analyze diffusion in the CA1 region of hippocampus where stratum pyramidale occupied by the bodies of principal neurons is flanked by stratum radiatum and stratum oriens. Extracellular diffusion in the CA1 region was measured in vitro by real-time iontophoretic and real-time pressure methods, and numerical analysis found that stratum pyramidale had a significantly smaller extracellular volume fraction (alpha=0.127) and lower diffusion permeability (theta=0.327) than the other two layers (alpha=0.218, theta=0.447). Stratum pyramidale thus functioned as a diffusion barrier for molecules attempting to cross it. We also demonstrate that unless the detailed properties of all layers are taken into account when diffusion experiments are interpreted, the extracted apparent parameters of the extracellular space lose their physical meaning and capacity to describe any individual layer. Such apparent parameters depend on diffusion distance and direction, giving a false impression of microscopic anisotropy and non-Gaussian behavior. This finding has implications for all diffusion mediated physiological processes as well as for other diffusion methods including integrative optical imaging and diffusion-weighted magnetic resonance imaging.
PMCID:3288711
PMID: 22230768
ISSN: 0165-0270
CID: 157477
Lithium prevents long-term neural and behavioral pathology induced by early alcohol exposure
Fetal alcohol exposure can cause developmental defects in offspring known as fetal alcohol spectrum disorder (FASD). FASD symptoms range from obvious facial deformities to changes in neuroanatomy and neurophysiology that disrupt normal brain function and behavior. Ethanol exposure at postnatal day 7 in C57BL/6 mice induces neuronal cell death and long-lasting neurobehavioral dysfunction. Previous work has demonstrated that early ethanol exposure impairs spatial memory task performance into adulthood and perturbs local and interregional brain circuit integrity in the olfacto-hippocampal pathway. Here we pursue these findings to examine whether lithium prevents anatomical, neurophysiological, and behavioral pathologies that result from early ethanol exposure. Lithium has neuroprotective properties that have been shown to prevent ethanol-induced apoptosis. Here we show that mice co-treated with lithium on the same day as ethanol exposure exhibit dramatically reduced acute neurodegeneration in the hippocampus and retain hippocampal-dependent spatial memory as adults. Lithium co-treatment also blocked ethanol-induced disruption in synaptic plasticity in slice recordings of hippocampal CA1 in the adult mouse brain. Moreover, long-lasting dysfunctions caused by ethanol in olfacto-hippocampal networks, including sensory-evoked oscillations and resting state coherence, were prevented in mice co-treated with lithium. Together, these results provide behavioral and physiological evidence that lithium is capable of preventing or reducing immediate and long-term deleterious consequences of early ethanol exposure on brain function.
PMCID:3294020
PMID: 22266347
ISSN: 0306-4522
CID: 159832
Evidence for an all-or-none perceptual response: single-trial analyses of magnetoencephalography signals indicate an abrupt transition between visual perception and its absence
Whether consciousness is an all-or-none or graded phenomenon is an area of inquiry that has received considerable interest in neuroscience and is as of yet, still debated. In this magnetoencephalography (MEG) study we used a single stimulus paradigm with sub-threshold, threshold and supra-threshold duration inputs to assess whether stimulus perception is continuous with or abruptly differentiated from unconscious stimulus processing in the brain. By grouping epochs according to stimulus identification accuracy and exposure duration, we were able to investigate whether a high-amplitude perception-related cortical event was (1) only evoked for conditions where perception was most probable, (2) had invariant amplitude once evoked and (3) was largely absent for conditions where perception was least probable (criteria satisfying an all-on-none hypothesis). We found that averaged evoked responses showed a gradual increase in amplitude with increasing perceptual strength. However, single-trial analyses demonstrated that stimulus perception was correlated with an all-or-none response, the temporal precision of which increased systematically as perception transitioned from ambiguous to robust states. Due to poor signal-to-noise resolution of single-trial data, whether perception-related responses, whenever present, were invariant in amplitude could not be unambiguously demonstrated. However, our findings strongly suggest that visual perception of simple stimuli is associated with an all-or-none cortical-evoked response the temporal precision of which varies as a function of perceptual strength
PMCID:4077720
PMID: 22020091
ISSN: 1873-7544
CID: 145694
Control of timing, rate and bursts of hippocampal place cells by dendritic and somatic inhibition
A consortium of inhibitory neurons control the firing patterns of pyramidal cells, but their specific roles in the behaving animal are largely unknown. We performed simultaneous physiological recordings and optogenetic silencing of either perisomatic (parvalbumin (PV) expressing) or dendrite-targeting (somatostatin (SOM) expressing) interneurons in hippocampal area CA1 of head-fixed mice actively moving a treadmill belt rich with visual-tactile stimuli. Silencing of either PV or SOM interneurons increased the firing rates of pyramidal cells selectively in their place fields, with PV and SOM interneurons having their largest effect during the rising and decaying parts of the place field, respectively. SOM interneuron silencing powerfully increased burst firing without altering the theta phase of spikes. In contrast, PV interneuron silencing had no effect on burst firing, but instead shifted the spikes' theta phase toward the trough of theta. These findings indicate that perisomatic and dendritic inhibition have distinct roles in controlling the rate, burst and timing of hippocampal pyramidal cells.
PMCID:4919905
PMID: 22446878
ISSN: 1097-6256
CID: 169687
