Neurosciences Commons^™

Mirror Reversal And Visual Rotation Are Learned And Consolidated Via Separate Mechanisms: Recalibrating Or Learning De Novo?, Sebastian Telgen, Darius Parvin, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Motor learning tasks are often classified into adaptation tasks, which involve the recalibration of an existing control policy (the mapping that determines both feedforward and feedback commands), and skill-learning tasks, requiring the acquisition of new control policies. We show here that this distinction also applies to two different visuomotor transformations during reaching in humans: Mirror-reversal (left-right reversal over a mid-sagittal axis) of visual feedback versus rotation of visual feedback around the movement origin. During mirror-reversal learning, correct movement initiation (feedforward commands) and online corrections (feedback responses) were only generated at longer latencies. The earliest responses were directed into a nonmirrored …

Targeting The Small- And Intermediate Conductance Ca2+- Activated Potassium Channels: The Drug Binding Pocket At The Channel/Calmodulin Interface, Meng Cui, Guangrong Qin, Kunqian Yu, M. Scott Bowers, Miao Zhang

Pharmacy Faculty Articles and Research

The small- and intermediate-conductance Ca 2+ -activated potassium (SK/IK) channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca 2+ sensitivity of the SK/IK channels stems from a constitutively bound Ca 2+ -binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been …

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.

Brain Death Determination, Bethani Knipfer

Nursing Student Class Projects (Formerly MSN)

Patient MR was a seventeen year old female involved in a motor vehicle collision which resulted in a traumatic brain injury leading to declaration of brain death. The pathophysiology behind the traumatic brain injury, the concept and use of a brain tissue monitoring device, and the tests used in the declaration of brain death will be explored. When brain death is determined, the patient has the opportunity to become an organ donor. Thousands of people are waiting for organs to become available. This is a huge healthcare concern that may be decreased if the general public is more educated regarding …

Dopaminergic Therapy Affects Learning And Impulsivity In Parkinson's Disease., Nole M Hiebert, Ken N Seergobin, Andrew Vo, Hooman Ganjavi, Penny A Macdonald

Brain and Mind Institute Researchers' Publications

OBJECTIVE: The aim was to examine the effect of dopaminergic medication on stimulus-response learning versus performing decisions based on learning.

METHOD: To see the effect of dopaminergic therapy on stimulus-response learning and response selection, participants with Parkinson's disease (PD) were either tested on and/or off their prescribed dose of dopaminergic therapy during different testing days. Forty participants with PD and 34 healthy controls completed the experiment on consecutive days. On Day 1, participants learned to associate abstract images with spoken, "right" or "left" responses via feedback (Session 1). On Day 2, participants recalled these responses (Session 2) and indicated the …

Developmental Stress, Condition, And Birdsong: A Case Study In Song Sparrows., Kim L Schmidt, Elizabeth A Macdougall-Shackleton, Shawn P Kubli, Scott A Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

Sexual-selection theory posits that ornaments and displays can reflect a signaler's condition, which in turn is affected both by recent and developmental conditions. Moreover, developmental conditions can induce correlations between sexually selected and other traits if both types of traits exhibit developmental phenotypic plasticity in response to stressors. Thus, sexually selected traits may reflect recent and/or developmental characteristics of signalers. Here, we review data on the relationships between birdsong, a sexually selected trait, and developmental and current condition of birds from a long-term study of a population of song sparrows (Melospiza melodia). Field studies of free-living birds indicate that the …

Differences In Brainstem Level Encoding Of Am And Fm Signals In A Rat Model For Dyslexia, Stephen Anthony Chabot

Open Access Theses

Developmental dyslexia is a language learning disorder that affects a significant portion of the population. Many subjects who suffer from dyslexia show auditory processing deficits as children, some of which persist into adulthood, which impair their ability to learn one or more aspects of language. There is evidence that some types of training can correct the auditory processing deficits and bring the subject to a normal reading or speaking proficiency for their age group. One common rodent model for dyslexia is the cortical freeze lesion model. This model induces a lesion in the rat cortex similar to the microgyria present …

Dynamics Of Alpha Control: Preparatory Suppression Of Posterior Alpha Oscillations By Frontal Modulators Revealed With Combined Eeg And Event-Related Optical Signal, Kyle E. Mathewson, Diane M. Beck, Tony Ro, Edward L. Maclin, Kathy A. Low, Monica Fabiani, Gabriele Gratton

Publications and Research

We investigated the dynamics of brain processes facilitating conscious experience of external stimuli. Previously, we proposed that alpha (8–12 Hz) oscillations, which fluctuate with both sustained and directed attention, represent a pulsed inhibition of ongoing sensory brain activity. Here we tested the prediction that inhibitory alpha oscillations in visual cortex are modulated by top–down signals from frontoparietal attention networks. We measured modulations in phase-coherent alpha oscillations from superficial frontal, parietal, and occipital cortices using the event-related optical signal (EROS), a measure of neuronal activity affording high spatiotemporal resolution, along with concurrently recorded EEG, while participants performed a visual target detection …

“Me & My Brain”: Exposing NeuroscienceʼS Closet Dualism, Liad Mudrik, Uri Maoz

Psychology Faculty Articles and Research

Our intuitive concept of the relations between brain and mind is increasingly challenged by the scientific world view. Yet, although few neuroscientists openly endorse Cartesian dualism, careful reading reveals dualistic intuitions in prominent neuroscientific texts. Here, we present the “double-subject fallacy”: treating the brain and the entire person as two independent subjects who can simultaneously occupy divergent psychological states and even have complex interactions with each other—as in “my brain knew before I did.” Although at first, such writing may appear like harmless, or even cute, shorthand, a closer look suggests that it can be seriously misleading. Surprisingly, this confused …

Swimming Against The Tide: Investigations Of The C-Bouton Synapse, Adam S. Deardorff, Shannon H. Romer, Patrick M. Sonner, Robert E. W. Fyffe

Neuroscience, Cell Biology & Physiology Faculty Publications

C-boutons are important cholinergic modulatory loci for state-dependent alterations in motoneuron firing rate. m2 receptors are concentrated postsynaptic to C-boutons, and m2 receptor activation increases motoneuron excitability by reducing the action potential afterhyperpolarization. Here, using an intensive review of the current literature as well as data from our laboratory, we illustrate that C-bouton postsynaptic sites comprise a unique structural/functional domain containing appropriate cellular machinery (a “signaling ensemble”) for cholinergic regulation of outward K⁺ currents. Moreover, synaptic reorganization at these critical sites has been observed in a variety of pathologic states. Yet despite recent advances, there are still great challenges …

The Significance Of Dynamical Architecture For Adaptive Responses To Mechanical Loads During Rhythmic Behavior, Kendrick M. M. Shaw, David N. Lyttle, Jeffrey P. Gill, Miranda J. Cullins, Jeffrey M. Mcmanus, Hui Lu, Peter J. Thomas, Hillel J. Chiel

Faculty Scholarship

Many behaviors require reliably generating sequences of motor activity while adapting the activity to incoming sensory information. This process has often been conceptually explained as either fully dependent on sensory input (a chain reflex) or fully independent of sensory input (an idealized central pattern generator, or CPG), although the consensus of the field is that most neural pattern generators lie somewhere between these two extremes. Many mathematical models of neural pattern generators use limit cycles to generate the sequence of behaviors, but other models, such as a heteroclinic channel (an attracting chain of saddle points), have been suggested. To explore …

Sharp Emergence Of Feature-Selective Sustained Activity Along The Dorsal Visual Pathway., Diego Mendoza-Halliday, Santiago Torres, Julio C Martinez-Trujillo

Brain and Mind Institute Researchers' Publications

Sustained activity encoding visual working memory representations has been observed in several cortical areas of primates. Where along the visual pathways this activity emerges remains unknown. Here we show in macaques that sustained spiking activity encoding memorized visual motion directions is absent in direction-selective neurons in early visual area middle temporal (MT). However, it is robustly present immediately downstream, in multimodal association area medial superior temporal (MST), as well as and in the lateral prefrontal cortex (LPFC). This sharp emergence of sustained activity along the dorsal visual pathway suggests a functional boundary between early visual areas, which encode sensory inputs, …

Role Of Astrocyte Network In Edema After Juvenile Traumatic Brain Injury, Andrew Minoru Fukuda

Loma Linda University Electronic Theses, Dissertations & Projects

Juvenile traumatic brain injury (jTBI) is the leading cause of death and disability in young children and adolescents. Despite its lasting detrimental effects on the developing brain, no pharmacological treatment exists. One of the pathological hallmarks of jTBI is edema. Astrocytes play a key role in the edema process, and have been hypothesized that numerous astrocyte networks allow communication and propagation of edema and secondary injury spread. Two key astrocyte proteins are hypothesized to have a central role in the edema process: Aquaporin 4 (AQP4) and Connexin 43 (Cx43). AQP4 is expressed extensively in astrocyte endfeet, which surrounds the blood …

Cyclic Ovarian Hormone Modulation Of Supraspinal Δ9-Tetrahydrocannabinol-Induced Antinociception And Cannabinoid Receptor Binding In The Female Rat, Alexa A. Wakley, Alisha A. Mcbride, Linda K. Vaughn, Rebecca M. Craft

Biomedical Sciences Faculty Research and Publications

Estrous cycle-related fluctuations in delta-9-tetrahydrocannabinol (THC)-induced antinociception have been observed in the rat. The aim of this study was to determine which major ovarian hormone modulates the antinociceptive effects of i.c.v. THC, and whether hormone modulation of THC's behavioral effects could be due to changes in brain cannabinoid receptors (CBr). Vehicle (oil) or hormones (estradiol or progesterone, or both) were administered to female rats on days 3 and 7 post-ovariectomy. On the morning or afternoon of day 8 or day 9, vehicle or THC (100 μg) was administered i.c.v. Paw pressure, tail withdrawal, locomotor activity and catalepsy tests were conducted …

Stress-Induced Cocaine Seeking Requires A Beta-2 Adrenergic Receptor-Regulated Pathway From The Ventral Bed Nucleus Of The Stria Terminalis That Regulates Crf Actions In The Ventral Tegmental Area, Oliver Vranjkovic, Paul J. Gasser, Clayton H. Gerndt, David A. Baker, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

The ventral bed nucleus of the stria terminalis (vBNST) has been implicated in stress-induced cocaine use. Here we demonstrate that, in the vBNST, corticotropin releasing factor (CRF) is expressed in neurons that innervate the ventral tegmental area (VTA), a site where the CRF receptor antagonist antalarmin prevents the reinstatement of cocaine seeking by a stressor, intermittent footshock, following intravenous self-administration in rats. The vBNST receives dense noradrenergic innervation and expresses β adrenergic receptors (ARs). Footshock-induced reinstatement was prevented by bilateral intra-vBNST injection of the β-2 AR antagonist, ICI-118,551, but not the β-1 AR antagonist, betaxolol. Moreover, bilateral intra-vBNST injection of …

Modeling Of The Dorsal Gradient Across Species Reveals Interaction Between Embryo Morphology And Toll Signaling Pathway During Evolution, Priscilla Ambrosi, Juan Sebastian Chahda, Hannah R. Koslen, Hillel J. Chiel, Claudia Mieko Mizutani

Faculty Scholarship

Morphogenetic gradients are essential to allocate cell fates in embryos of varying sizes within and across closely related species. We previously showed that the maternal NF-κB/Dorsal (Dl) gradient has acquired different shapes in Drosophila species, which result in unequally scaled germ layers along the dorso-ventral axis and the repositioning of the neuroectodermal borders. Here we combined experimentation and mathematical modeling to investigate which factors might have contributed to the fast evolutionary changes of this gradient. To this end, we modified a previously developed model that employs differential equations of the main biochemical interactions of the Toll (Tl) signaling pathway, which …

Human Premotor Areas Parse Sequences Into Their Spatial And Temporal Features., Katja Kornysheva, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Skilled performance is characterized by precise and flexible control of movement sequences in space and time. Recent theories suggest that integrated spatio-temporal trajectories are generated by intrinsic dynamics of motor and premotor networks. This contrasts with behavioural advantages that emerge when a trained spatial or temporal feature of sequences is transferred to a new spatio-temporal combination arguing for independent neural representations of these sequence features. We used a new fMRI pattern classification approach to identify brain regions with independent vs integrated representations. A distinct regional dissociation within motor areas was revealed: whereas only the contralateral primary motor cortex exhibited unique …

Bdnf Maintains Adult Taste Innervation And Is Required For Taste Nerve Regeneration After Injury., Lingbin Meng

Electronic Theses and Dissertations

Brain derived neurotropic factor (BDNF) is required for the gustatory neuron survival,target innervation, and taste bud maintenance during development. However, whether BDNF has any function in the adult gustatory system in normal conditions or after nerve injury is unclear. To address these issues, I inducibly removed BDNF in all cells expressing BDNF in adult mice. In the experimental animals, Bdnf expression decreased to 5% of control mice in the lingual epithelium and geniculate ganglion (p< 0.01) at both two weeks and ten weeks after tamoxifen administration. I found no effect on taste bud morphology at four weeks following Bdnf gene deletion. However, ten weeks following Bdnf gene deletion, P2X3-positive and TUJ1-positive gustatory innervation to individual taste buds was reduced by nearly half (each with p < 0.01) and both taste bud volume and taste cell number decreased 30% (each with p< 0.01). These experiments demonstrate that BDNF is required for maintenance of normal levels of taste innervation and normal taste bud morphology in adulthood. In addition, taste cells expressing PLCß2 (phospholipase C ß2), a marker for taste cells that respond to sweet, bitter and umami, did not decrease after Bdnf gene deletion in the adult. Thus, the missing taste cells are of another type. This indicates that taste cell loss is not uniform across the various taste cell types, even if nearly all taste cell types receive the P2X3 and TUJ1 innervation. Since BDNF is required for initial innervation of the taste system and supports taste bud innervation and size in adulthood, it could also be required for nerve reinnervation after injury. To determine if Bdnf is still expressed following nerve section, the chorda tympani nerve (taste nerve) was sectioned and Bdnf level was detected with Real Time RT-PCR. Bdnf continued to be expressed at normal levels from two days to two months post-surgery in both geniculate ganglion and tongue epithelium. Therefore, BDNF could be involved with chorda tympani regeneration. To determine if this was the case, the Bdnf gene was deleted in adult inducible transgenic mice (under the control of a Ubiquitin promoter) two weeks before chorda tympani nerve section. Taste bud number was reduced by half in all genotypes at two weeks post-surgery (p < 0.01). For the remaining taste buds, gustatory innervation was nearly gone with only a little innervation from the trigeminal nerve remaining in the taste bud (p < 0.01). Taste bud volume (p < 0.01) and taste cell number (p< 0.01) were reduced by half for both control and experimental genotypes. Eight weeks post-surgery, taste bud number recovered in mice without Bdnf gene deletion, but did not recover in mice following Bdnf gene deletion (p < 0.01). Gustatory nerve innervation returned in 70% of the taste buds in control mice (p< 0.01). For those reinnervated taste buds, both taste bud volume and taste cell number increased to normal levels. However, in mice lacking the Bdnf gene, gustatory fibers only reinnervated 7.8% of the taste buds (p < 0.01); for most uninnervated taste buds, both taste bud volume and taste cell number remained small. These experiments demonstrate that BDNF is crucial for promoting regeneration of gustatory nerve fibers in adulthood. Following gustatory nerve section, considerable adult plasticity has been observed on the contralateral side including enlarged taste buds with more cells (Guagliardo and Hill, 2007). To determine if this anatomical change was associated with alter Bdnf expression. I examined Bdnf level in the geniculate ganglion and tongue epithelium on the contralateral side following chorda tympani nerve section. Results showed Bdnf expression increased two fold at two weeks post-surgery in geniculate ganglion on the contralateral side (p < 0.05), indicating BDNF may involve with the observed plastic changes. To determine if the increase in taste bud size was associated with increased innervation and/or regulated by BDNF, the Bdnf gene was then deleted in inducible knockout mice before nerve surgery, and taste bud size and amount of innervation were measured on the contralateral side. The results showed taste bud volume, taste cell number and a marker for nerve fibers all increased on the contralateral side in mice without Bdnf gene deletion at eight weeks post-surgery. This indicates that larger taste buds could be supported by increased TUJ1 positive fibers from trigeminal nerve. In addition, in mice lacking Bdnf, taste bud volume, taste cell number and innervation did not increase on the contralateral side after surgery, which indicates that Bdnf may contribute to larger taste buds on the contralateral side following nerve section by supporting increased innervation to the larger taste buds.

The Effect Of Acute Lps-Induced Immune Activation And Brain Insulin Signaling Disruption In A Diabetic Model Of Alzheimer's Disease, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive cognitive impairments and pathological hallmarks that include amyloid plaques, neurofibrillary tangles, and neuronal loss. Several well-known mutations exist that lead to early-onset familial AD (fAD). However, these cases only account for a small percentage of total AD cases. The vast majority of AD cases are sporadic in origin (sAD) and are less clearly influenced by a single mutation but rather some combination of genetic and environmental risk.

The etiology of sAD remains unclear but numerous risk factors have been identified that increase the chance of developing AD. Among these risk …

Alternating Current And Infrared Produce An Onset-Free Reversible Nerve Block, Emilie H. Lothet, Kevin L. Kilgore, Niloy Bhadra, Narendra Bhadra, Tina Vrabec, Yves T. Wang, Michael W. Jenkins, Hillel J. Chiel

Faculty Scholarship

Nerve block can eliminate spasms and chronic pain. Kilohertz frequency alternating current (KHFAC) produces a safe and reversible nerve block. However, KHFAC-induced nerve block is associated with an undesirable onset response. Optical inhibition using infrared (IR) laser light can produce nerve block without an onset response, but heats nerves. Combining KHFAC with IR inhibition [alternating current and infrared (ACIR)] produces a rapidly reversible nerve block without an onset response. ACIR can be used to rapidly and reversibly provide onset-free nerve block in the unmyelinated nerves of the marine mollusk Aplysia californica and may have significant advantages over either modality alone. …