Vanderbilt Brain Institute

Nashville, TN, United States

Vanderbilt Brain Institute

Nashville, TN, United States
Time filter
Source Type

Matthews R.T.,Vanderbilt University | Winder D.G.,Vanderbilt Brain Institute | Winder D.G.,Vanderbilt University
Journal of Neuroscience | Year: 2013

A growing literature suggests that catecholamines and corticotropin-releasing factor (CRF) interact in a serial manner to activate the bed nucleus of the stria terminalis (BNST) to drive stress- or cue-induced drug- and alcohol-seeking behaviors. Data suggest that these behaviors are driven in part by BNST projections to the ventral tegmental area (VTA). Together, these findings suggest the existence of a CRF-signaling pathway within the BNST that is engaged by catecholamines and regulates the activity of BNST neurons projecting to the VTA. Here we test three aspects of this model to determine: (1) whether catecholamines modify CRF neuron activity in the BNST; (2) whether CRF regulates excitatory drive onto VTA-projecting BNST neurons; and (3) whether this system is altered by ethanol exposure and withdrawal. A CRF neuron fluorescent reporter strategy was used to identify BNST CRF neurons for whole-cell patch-clamp analysis in acutely prepared slices. Using this approach, we found that both dopamine and isoproterenol significantly depolarized BNST CRF neurons. Furthermore, using a fluorescent microsphere-based identification strategy we found that CRF enhances the frequency of spontaneous EPSCs onto VTA-projecting BNST neurons in naive mice. This action of CRF was occluded during acute withdrawal from chronic intermittent ethanol exposure. These findings suggest that dopamine and isoproterenol may enhance CRF release from local BNST sources, leading to enhancement of excitatory neurotransmission on VTA-projecting neurons, and that this pathway is engaged by patterns of alcohol exposure and withdrawal known to drive excessive alcohol intake. © 2013 the authors.

Stevenson R.A.,Vanderbilt University | Stevenson R.A.,Vanderbilt Brain Institute | Stevenson R.A.,Vanderbilt Kennedy Center | Stevenson R.A.,University of Toronto | And 11 more authors.
Journal of Neuroscience | Year: 2014

The new DSM-5 diagnostic criteria for autism spectrum disorders (ASDs) include sensory disturbances in addition to the well-established language, communication, and social deficits. One sensory disturbance seen in ASD is an impaired ability to integrate multisensory information into a unified percept. This may arise from an underlying impairment in which individuals with ASD have difficulty perceiving the temporal relationship between cross-modal inputs, an important cue for multisensory integration. Such impairments in multisensory processing may cascade into higher-level deficits, impairing day-to-day functioning on tasks, such as speech perception. To investigate multisensory temporal processing deficits in ASD and their links to speech processing, the current study mapped performance on a number of multisensory temporal tasks (with both simple and complex stimuli) onto the ability of individuals with ASD to perceptually bind audiovisual speech signals. High-functioning children with ASD were compared with a group of typically developing children. Performance on the multisensory temporal tasks varied with stimulus complexity for both groups; less precise temporal processing was observed with increasing stimulus complexity. Notably, individuals with ASD showed a speech-specific deficit in multisensory temporal processing. Most importantly, the strength of perceptual binding of audiovisual speech observed in individuals with ASD was strongly related to their low-level multisensory temporal processing abilities. Collectively, the results represent the first to illustrate links between multisensory temporal function and speech processing in ASD, strongly suggesting that deficits in low-level sensory processing may cascade into higher-order domains, such as language and communication. © 2014 the authors.

Silberman Y.,Vanderbilt University | Silberman Y.,Vanderbilt Brain Institute | Winder D.G.,Vanderbilt University | Winder D.G.,Vanderbilt Brain Institute
Neuropharmacology | Year: 2013

Glutamatergic neurotransmission in the central nucleus of the amygdala (CeA) plays an important role in many behaviors including anxiety, memory consolidation and cardiovascular responses. While these behaviors can be modulated by corticotropin releasing factor (CRF) and catecholamine signaling, the mechanism(s) by which these signals modify CeA glutamatergic neurotransmission remains unclear. Utilizing whole-cell patch-clamp electrophysiology recordings from neurons in the lateral subdivision of the CeA (CeAL), we show that CRF, dopamine (DA) and the β-adrenergic receptor agonist isoproterenol (ISO) all enhance the frequency of spontaneous excitatory postsynaptic currents (sEPSC) without altering sEPSC kinetics, suggesting they increase presynaptic glutamate release. The effect of CRF on sEPSCs was mediated by a combination of CRFR1 and CRFR2 receptors. While previous work from our lab suggests that CRFRs mediate the effect of catecholamines on excitatory transmission in other subregions of the extended amygdala, blockade of CRFRs in the CeAL failed to significantly alter effects of DA and ISO on glutamatergic transmission. These findings suggest that catecholamine and CRF enhancement of glutamatergic transmission onto CeAL neurons occurs via distinct mechanisms. While CRF increased spontaneous glutamate release in the CeAL, CRF caused no significant changes to optogenetically evoked glutamate release in this region. The dissociable effects of CRF on different types of glutamatergic neurotransmission suggest that CRF may specifically regulate spontaneous excitatory transmission. © 2013 Elsevier Ltd. All rights reserved.

Stevenson R.A.,Vanderbilt University | Stevenson R.A.,Vanderbilt Kennedy Center | Stevenson R.A.,Vanderbilt Brain Institute | Wallace M.T.,Vanderbilt University | And 2 more authors.
Experimental Brain Research | Year: 2013

The ability of human sensory systems to integrate information across the different modalities provides a wide range of behavioral and perceptual benefits. This integration process is dependent upon the temporal relationship of the different sensory signals, with stimuli occurring close together in time typically resulting in the largest behavior changes. The range of temporal intervals over which such benefits are seen is typically referred to as the temporal binding window (TBW). Given the importance of temporal factors in multisensory integration under both normal and atypical circumstances such as autism and dyslexia, the TBW has been measured with a variety of experimental protocols that differ according to criterion, task, and stimulus type, making comparisons across experiments difficult. In the current study, we attempt to elucidate the role that these various factors play in the measurement of this important construct. The results show a strong effect of stimulus type, with the TBW assessed with speech stimuli being both larger and more symmetrical than that seen using simple and complex non-speech stimuli. These effects are robust across task and statistical criteria and are highly consistent within individuals, suggesting substantial overlap in the neural and cognitive operations that govern multisensory temporal processes. © 2013 Springer-Verlag Berlin Heidelberg.

Blackford J.U.,Vanderbilt University | Allen A.H.,Vanderbilt University | Cowan R.L.,Vanderbilt University | Avery S.N.,Vanderbilt University | Avery S.N.,Vanderbilt Brain Institute
Social Cognitive and Affective Neuroscience | Year: 2013

Habituation is a basic form of learning that reflects the adaptive reduction in responses to a stimulus that is neither threatening nor rewarding. Extremely shy, or inhibited individuals, are typically slow to acclimate to new people, a behavioral pattern that may reflect slower habituation to novelty. To test this hypothesis, we used functional magnetic resonance imaging to examine habituation to neutral faces in 39 young adults with either an extreme inhibited or extreme uninhibited temperament. Our investigation focused on two key brain regions involved in response to novelty-the amygdala and the hippocampus. Habituation to neutral faces in the amygdala and hippocampus differed significantly by temperament group. Individuals with an uninhibited temperament demonstrated habituation in both the amygdala and hippocampus, as expected. In contrast, in individuals with an inhibited temperament, the amygdala and hippocampus failed to habituate across repeated presentations of faces. The failure of the amygdala and hippocampus to habituate to faces represents a novel neural substrate mediating the behavioral differences seen in individuals with an inhibited temperament. We propose that this failure to habituate reflects a social learning deficit in individuals with an inhibited temperament and provides a possible mechanism for increased risk for social anxiety. © The Author (2012). Published by Oxford University Press.

Godlove D.C.,Vanderbilt Brain Institute | Maier A.,Vanderbilt Brain Institute | Woodman G.F.,Vanderbilt Brain Institute | Schall J.D.,Vanderbilt Brain Institute
Journal of Neuroscience | Year: 2014

Weinvestigated whether a frontal area that lacks granular layer IV, supplementary eye field, exhibits features of laminar circuitry similar to those observed in primary sensory areas. We report, for the first time, visually evoked local field potentials (LFPs) and spiking activity recorded simultaneously across all layers of agranular frontal cortex using linear electrode arrays. We calculated current source density from the LFPs and compared the laminar organization of evolving sinks to those reported in sensory areas. Simultaneous, transient synaptic current sinks appeared first in layers III and V followed by more prolonged current sinks in layers I/II and VI. We also found no variation of single-or multi-unit visual response latency across layers, and putative pyramidal neurons and interneurons displayed similar response latencies. Many units exhibited pronounced discharge suppression that was strongest in superficial relative to deep layers. Maximum discharge suppression also occurred later in superficial than in deep layers. These results are discussed in the context of the canonical cortical microcircuit model originally formulated to describe early sensory cortex. The data indicate that agranular cortex resembles sensory areas in certain respects, but the cortical microcircuit is modified in nontrivial ways. © 2014 the authors.

News Article | October 27, 2016

The probe, which was developed by a team of Vanderbilt scientists, is a genetically modified form of luciferase, the enzyme that a number of other species including fireflies use to produce light. It is described in a paper published in the journal Nature Communications on Oct. 27. The scientists created the technique as a new and improved method for tracking the interactions within large neural networks in the brain. "For a long time neuroscientists relied on electrical techniques for recording the activity of neurons. These are very good at monitoring individual neurons but are limited to small numbers of neurons. The new wave is to use optical techniques to record the activity of hundreds of neurons at the same time," said Carl Johnson, Stevenson Professor of Biological Sciences, who headed the effort. "Most of the efforts in optical recording use fluorescence, but this requires a strong external light source which can cause the tissue to heat up and can interfere with some biological processes, particularly those that are light sensitive," he said. Based on their research on bioluminescence in "a scummy little organism, the green alga Chlamydomonas, that nobody cares much about" Johnson and his colleagues realized that if they could combine luminescence with optogenetics -- a new biological technique that uses light to control cells, particularly neurons, in living tissue -- they could create a powerful new tool for studying brain activity. "There is an inherent conflict between fluorescent techniques and optogenetics. The light required to produce the fluorescence interferes with the light required to control the cells," said Johnson. "Luminescence, on the other hand, works in the dark!" Johnson and his collaborators -- Associate Professor Donna Webb, Research Assistant Professor Shuqun Shi, post-doctoral student Jie Yang and doctoral student Derrick Cumberbatch in biological sciences and Professor Danny Winder and postdoctoral student Samuel Centanni in molecular physiology and biophysics - genetically modified a type of luciferase obtained from a luminescent species of shrimp so that it would light up when exposed to calcium ions. Then they hijacked a virus that infects neurons and attached it to their sensor molecule so that the sensors are inserted into the cell interior. The researchers picked calcium ions because they are involved in neuron activation. Although calcium levels are high in the surrounding area, normally they are very low inside the neurons. However, the internal calcium level spikes briefly when a neuron receives an impulse from one of its neighbors. They tested their new calcium sensor with one of the optogenetic probes (channelrhodopsin) that causes the calcium ion channels in the neuron's outer membrane to open, flooding the cell with calcium. Using neurons grown in culture they found that the luminescent enzyme reacted visibly to the influx of calcium produced when the probe was stimulated by brief light flashes of visible light. To determine how well their sensor works with larger numbers of neurons, they inserted it into brain slices from the mouse hippocampus that contain thousands of neurons. In this case they flooded the slices with an increased concentration of potassium ions, which causes the cell's ion channels to open. Again, they found that the sensor responded to the variations in calcium concentrations by brightening and dimming. "We've shown that the approach works," Johnson said. "Now we have to determine how sensitive it is. We have some indications that it is sensitive enough to detect the firing of individual neurons, but we have to run more tests to determine if it actually has this capability." The work was funded by National Institutes of Health grants R21 DA034446, R21 MH107713, R01 GM092914, National Science Foundation grant DBI-1450897 and a grant from the Vanderbilt Brain Institute.

Stevenson R.A.,Vanderbilt University | Stevenson R.A.,Vanderbilt Kennedy Center | Stevenson R.A.,Vanderbilt Brain Institute | Schlesinger J.J.,Vanderbilt Kennedy Center | And 2 more authors.
Anesthesiology | Year: 2013

Background: Anesthesiology requires performing visually oriented procedures while monitoring auditory information about a patient's vital signs. A concern in operating room environments is the amount of competing information and the effects that divided attention has on patient monitoring, such as detecting auditory changes in arterial oxygen saturation via pulse oximetry. Methods: The authors measured the impact of visual attentional load and auditory background noise on the ability of anesthesia residents to monitor the pulse oximeter auditory display in a laboratory setting. Accuracies and response times were recorded reflecting anesthesiologists' abilities to detect changes in oxygen saturation across three levels of visual attention in quiet and with noise. Results: Results show that visual attentional load substantially affects the ability to detect changes in oxygen saturation concentrations conveyed by auditory cues signaling 99 and 98% saturation. These effects are compounded by auditory noise, up to a 17% decline in performance. These deficits are seen in the ability to accurately detect a change in oxygen saturation and in speed of response. Conclusions: Most anesthesia accidents are initiated by small errors that cascade into serious events. Lack of monitor vigilance and inattention are two of the more commonly cited factors. Reducing such errors is thus a priority for improving patient safety. Specifically, efforts to reduce distractors and decrease background noise should be considered during induction and emergence, periods of especially high risk, when anesthesiologists has to attend to many tasks and are thus susceptible to error. © 2013, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.

Fougnie D.,Vanderbilt University | Asplund C.L.,Vanderbilt Brain Institute | Marois R.,Vanderbilt University
Journal of Vision | Year: 2010

An influential theory suggests that integrated objects, rather than individual features, are the fundamental units that limit our capacity to temporarily store visual information (S. J. Luck & E. K. Vogel, 1997). Using a paradigm that independently estimates the number and precision of items stored in working memory (W. Zhang & S. J. Luck, 2008), here we show that the storage of features is not cost-free. The precision and number of objects held in working memory was estimated when observers had to remember either the color, the orientation, or both the color and orientation of simple objects. We found that while the quantity of stored objects was largely unaffected by increasing the number of features, the precision of these representations dramatically decreased. Moreover, this selective deterioration in object precision depended on the multiple features being contained within the same objects. Such fidelity costs were even observed with change detection paradigms when those paradigms placed demands on the precision of the stored visual representations. Taken together, these findings not only demonstrate that the maintenance of integrated features is costly; they also suggest that objects and features affect visual working memory capacity differently. © ARVO.

Whyte A.,Vanderbilt Brain Institute | Jessen T.,Vanderbilt University | Varney S.,Vanderbilt University | Carneiro A.M.D.,Vanderbilt University
Neurochemistry International | Year: 2014

Dysfunctions in serotonin (5-hydroxytryptamine, 5-HT) systems have been associated with several psychiatric illnesses, including anxiety, depression, obsessive-compulsive disorders and autism spectrum disorders. Convergent evidence from genetic analyses of human subjects has implicated the integrin β3 subunit gene (ITGB3) as a modulator of serotonergic systems via genetic interactions with the 5-HT transporter gene (SLC6A4, SERT). While genetic interactions may result from contributions of each gene at several levels, we hypothesize that ITGB3 modulates the 5-HT system at the level of the synapse, through the actions of integrin αvβ3. Here we utilized a genetic approach in mouse models to examine Itgb3 contributions to SERT function both in the context of normal and reduced SERT expression. As integrin αvβ3 is expressed in postsynaptic membranes, we isolated synaptoneurosomes, which maintain intact pre- and post-synaptic associations. Citalopram binding revealed significant Slc6a4-driven reductions in SERT expression in midbrain synapses, whereas no significant changes were observed in hippocampal or cortical projections. Expecting corresponding changes to SERT function, we also measured 5-HT uptake activity in synaptoneurosomal preparations. Itgb3 single heterozygous mice displayed significant reductions in 5-HT Vmax, with no changes in Km, in midbrain preparations. However, in the presence of both Itgb3 and Slc6a4 heterozygozity, 5-HT uptake was similar to wild-type levels, revealing a significant Slc6a4 by Itgb3 genetic interaction in the midbrain. Similar findings were observed in cortical preparations, whereas in the hippocampus, most Vmax changes were driven solely by Slc6a4. Our findings provide evidence that integrin αvβ3 is involved in the regulation of serotonergic systems in some, but not all 5-HT synapses, revealing novel contributions to synaptic specificity within the central nervous system. © 2013 Elsevier Ltd. All rights reserved.

Loading Vanderbilt Brain Institute collaborators
Loading Vanderbilt Brain Institute collaborators