Neurosciences Commons^™

Calmodulin Enhances Ribbon Replenishment And Shapes Filtering Of Synaptic Transmission By Cone Photoreceptors., Matthew J. Van Hook, Caitlyn M. Parmelee, Minghui Chen, Karlene M. Cork, Carina Curto, Wallace B. Thoreson

Journal Articles: Pharmacology & Experimental Neuroscience

At the first synapse in the vertebrate visual pathway, light-evoked changes in photoreceptor membrane potential alter the rate of glutamate release onto second-order retinal neurons. This process depends on the synaptic ribbon, a specialized structure found at various sensory synapses, to provide a supply of primed vesicles for release. Calcium (Ca(2+)) accelerates the replenishment of vesicles at cone ribbon synapses, but the mechanisms underlying this acceleration and its functional implications for vision are unknown. We studied vesicle replenishment using paired whole-cell recordings of cones and postsynaptic neurons in tiger salamander retinas and found that it involves two kinetic mechanisms, the …

Adult Neurogenesis In The Four-Striped Mice (Rhabdomys Pumilio), Olatunbosun O. Olaleye, Amadi O. Ihunwo

Brain and Mind Institute

In this study, we investigated non-captive four-striped mice (Rhabdomys pumilio) for evidence that adult neurogenesis occurs in the adult brain of animal models in natural environment. Ki-67 (a marker for cell proliferation) and doublecortin (a marker for immature neurons) immunostaining confirmed that adult neurogenesis occurs in the active sites of subventricular zone of the lateral ventricle with the migratory stream to the olfactory bulb, and the subgranular zone of the dentate gyrus of the hippocampus. No Ki-67 proliferating cells were observed in the striatum substantia nigra, amygdala, cerebral cortex or dorsal vagal complex. Doublecortin-immunoreactive cells were observed in …

The Incentive Amplifying Effects Of Nicotine Are Reduced By Selective And Non-Selective Dopamine Antagonists In Rats, Matthew I. Palmatier, Marissa R. Kellicut, A. Brianna Sheppard, Russell W. Brown, Donita L. Robinson

ETSU Faculty Works

Nicotine is a psychomotor stimulant with ‘reinforcement enhancing’ effects — the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate …

Phosphate And Acidosis Act Synergistically To Depress Peak Power In Rat Muscle Fibers, Cassandra R. Nelson, Edward P. Debold, Robert H. Fitts

Biomedical Sciences Faculty Research and Publications

Skeletal muscle fatigue is characterized by the buildup of H⁺ and inorganic phosphate (P_i), metabolites that are thought to cause fatigue by inhibiting muscle force, velocity, and power. While the individual effects of elevated H⁺ or P_i have been well characterized, the effects of simultaneously elevating the ions, as occurs during fatigue in vivo, are still poorly understood. To address this, we exposed slow and fast rat skinned muscle fibers to fatiguing levels of H⁺ (pH 6.2) and P_i (30 mM) and determined the effects on contractile properties. At 30°C, elevated P_{i …}

Transcranial Magnetic Stimulation Of The Prefrontal Cortex In Awake Nonhuman Primates Evokes A Polysynaptic Neck Muscle Response That Reflects Oculomotor Activity At The Time Of Stimulation., Chao Gu, Brian D Corneil

Brain and Mind Institute Researchers' Publications

Transcranial magnetic stimulation (TMS) has emerged as an important technique in cognitive neuroscience, permitting causal inferences about the contribution of a given brain area to behavior. Despite widespread use, exactly how TMS influences neural activity throughout an interconnected network, and how such influences ultimately change behavior, remain unclear. The oculomotor system of nonhuman primates (NHPs) offers a potential animal model to bridge this gap. Here, based on results suggesting that neck muscle activity provides a sensitive indicator of oculomotor activation, we show that single pulses of TMS over the frontal eye fields (FEFs) in awake NHPs evoked rapid (within ∼25 …

Burning Pain Secondary To Clozapine Use: A Case Report., Bradley Linton, Rachel Fu, Penny A Macdonald, Hooman Ganjavi

Brain and Mind Institute Researchers' Publications

BACKGROUND: The first of the atypical antipsychotics introduced in the 1970s, clozapine remains the most efficacious neuroleptic to this day. However, serious and potentially fatal side effects have necessitated careful regular monitoring among prescribing clinicians. Some adverse effects (e.g. ischaemic bowel) remain under recognized, while newly identified adverse effects continue to be described in the literature.

CASE PRESENTATION: In this report, we describe a healthy 43-year old Caucasian male who experienced onset of a full body deep burning pain several months after the onset of treatment with clozapine. The pain worsened over time, ceased with cessation of treatment, and returned …

The Cost Of Moving Optimally: Kinematic Path Selection., Dinant A Kistemaker, Jeremy D Wong, Paul L Gribble

Brain and Mind Institute Researchers' Publications

It is currently unclear whether the brain plans movement kinematics explicitly or whether movement paths arise implicitly through optimization of a cost function that takes into account control and/or dynamic variables. Several cost functions are proposed in the literature that are very different in nature (e.g., control effort, torque change, and jerk), yet each can predict common movement characteristics. We set out to disentangle predictions of the different variables using a combination of modeling and empirical studies. Subjects performed goal-directed arm movements in a force field (FF) in combination with visual perturbations of seen hand position. This FF was designed …

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, …

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 …