Neuroscience and Neurobiology Commons^™

Role Of Trp Channels In Mediating The Calcium Signaling Response Of Brain Endothelial Cells To Mechanical Stretch, Jonathan Berrout

Dissertations and Theses (Open Access)

Traumatic brain injury (TBI) often results in disruption of the blood brain barrier (BBB), which is an integral component to maintaining the central nervous system homeostasis. Recently cytosolic calcium levels ([Ca²⁺]i), observed to elevate following TBI, have been shown to influence endothelial barrier integrity. However, the mechanism by which TBI-induced calcium signaling alters the endothelial barrier remains unknown. In the present study, an in vitro BBB model was utilized to address this issue. Exposure of cells to biaxial mechanical stretch, in the range expected for TBI, resulted in a rapid cytosolic calcium increase. Modulation of intracellular and extracellular …

Novel Use Of Dual Anti-Inflammatory Therapy To Overcome Drug Resistance And Improve Functional Recovery Following Spinal Cord Injury, Jennifer Dulin

Dissertations and Theses (Open Access)

Over 1.2 million Americans are currently living with a traumatic spinal cord injury (SCI). Despite the need for effective therapies, there are currently no proven effective treatments that can improve recovery of function in SCI patients. Many therapeutic compounds have shown promise in preclinical models of SCI, but all of these have fallen short in clinical trials.

P-glycoprotein (Pgp) is an active transporter expressed on capillary endothelial cell membranes at the blood-spinal cord barrier (BSCB). Pgp limits passive diffusion of blood-borne drugs into the CNS, by actively extruding drugs from the endothelial cell membrane. Pgp can become pathologically up-regulated, thus …

Population Coding In Laminar Cortical Circuits, Bryan J. Hansen

Dissertations and Theses (Open Access)

One of the fundamental questions in neuroscience is to understand how encoding of sensory inputs is distributed across neuronal networks in cerebral cortex to influence sensory processing and behavioral performance. The fact that the structure of neuronal networks is organized according to cortical layers raises the possibility that sensory information could be processed differently in distinct layers. The goal of my thesis research is to understand how laminar circuits encode information in their population activity, how the properties of the population code adapt to changes in visual input, and how population coding influences behavioral performance. To this end, we performed …

Parkinson’S Disease: Molecular Mechanisms And Treatments, Delia Vahey

Senior Honors Theses

Parkinson’s disease is a motor system disorder that is caused primarily by the loss of dopamine-producing brain cells. The most affected brain structure is the pars compacta of the substantia nigra. This area of the brain is essential to the control of voluntary movement, and so its impairment leads to symptoms such as tremors, rigidity, and impaired balance. The neuronal protein alpha-synuclein has been shown to be heavily involved in the pathogenesis of the disease at the cellular level. The currently available treatments for PD mainly target dopamine regulation, and there been no cure developed for the disease at present. …

Effects Of Cannabidiol On Mk-801-Induced Locomotor Sensitization In Mice, Sara K. Cronin

Scripps Senior Theses

Previous research has shown that cannabidiol (CBD), a non-psychoactive compound in the hemp plant Cannabis sativa, may be useful in treating drug craving, one of the hallmarks of drug addiction. However, the neural mechanism by which CBD attenuates craving is poorly understood. Studies from other laboratories have shown that neuroplastic changes associated with brain NMDA glutamate systems may at least partially serve as a neural mechanism for craving. In the current study, the noncompetitive NMDA receptor antagonist MK-801 maleate was used to induce locomotor sensitization, a form of NMDA glutamate-mediated neuroplasticity, in mice to test the sensitization-attenuating potential of …

The Neurobiology Of Decision-Making And Responsibility: Reconciling Mechanism And Mindedness, Michael N. Shadlen, Adina L. Roskies

Dartmouth Scholarship

This essay reviews recent developments in neurobiology which are beginning to expose the mechanisms that underlie some elements of decision-making that bear on attributions of responsibility. These “elements” have been mainly studied in simple perceptual decision tasks, which are performed similarly by humans and non-human primates. Here we consider the role of neural noise, and suggest that thinking about the role of noise can shift the focus of discussions of randomness in decision-making away from its role in enabling alternate possibilities and toward a potential grounding role for responsibility.

Detection Of Sk2 Channels On Hippocampal Neurons, Jamie L. Maciaszek

Master's Theses

Calcium-activated small conductance potassium channels (SK) are crucial for synaptic plasticity, sleep, and learning and memory (Hammond, Bond et al. 2006; Cueni, Canepari et al. 2008; Lin, Lujan et al. 2008). Despite the recent progress on SK channel physiology, the precise spatial organization of SK channels in neurons has remained unknown. Such knowledge is critical as the subcellular distribution of SK channels is an important determinant of neuronal excitability. Currently, there are no techniques to image ion channel distribution quantitatively at the nanometer scale in living cells. Here, it is demonstrated that integration of natural toxins with single molecule atomic …

Electrical Advantages Of Dendritic Spines, Allan T. Gulledge, Nicholas T. Carnevale, Greg J. Stuart

Dartmouth Scholarship

Many neurons receive excitatory glutamatergic input almost exclusively onto dendritic spines. In the absence of spines, the amplitudes and kinetics of excitatory postsynaptic potentials (EPSPs) at the site of synaptic input are highly variable and depend on dendritic location. We hypothesized that dendritic spines standardize the local geometry at the site of synaptic input, thereby reducing location-dependent variability of local EPSP properties. We tested this hypothesis using computational models of simplified and morphologically realistic spiny neurons that allow direct comparison of EPSPs generated on spine heads with EPSPs generated on dendritic shafts at the same dendritic locations. In all morphologies …

Brainstorm: Of Princesses And Football Players, John J. Medina Ph.D.

Brainstorm

Sports-­related head injuries are getting a lot of press these days. Learning from injuries sustained by prize fighters, hockey players, and American football players, researchers are beginning to understand there are severe consequences to sustained trauma on the mental life of professional athletes — even amateur, Saturday­afternoon athletes. Sports officials could do well to remember the cautionary tale I am about to relate here.

The Effects Of Prenatal Exposure To Altered Melatonin Levels On Hippocampal Gene Expression In The Male Rat, Anna Uehara

Honors Theses

The stability of the circadian rhythm for mammals depends on the levels of serotonin and melatonin, neurohormones that signal for lightness and darkness, respectively. Disruption in the stability of neurohormones has been shown to be a critical factor in psychopathological disorders in humans. For example, altering levels of melatonin in utero through administration of melatonin or the melatonin receptor antagonist, luzindole, has been shown to cause changes in developmental growth and adult behavior in the male rat. Analysis of relative adult hippocampal gene expression with RT-PCR revealed differences in ARNTL expression that suggested abnormality in clock gene expression of the …

Chemoarchitecture Of Hindbrain Autonomic Nuclei: Contiguous Mapping And Distribution Of Six Biomarkers In The Adult Male Rat, Sarah D. Chenausky^, Arshad M. Khan*

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Angioarchitecture Of The Adult Rat Neuroendocrine Hypothalamus, Nicolas D. Silva^, Arshad M. Khan*

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Stress-Induced Activation Of Distinct Subpopulations Of Neurons In The Basolateral Amygdala Of The Rat, Juan M. Bolanos^, Jameel N. Hamdan, Victor M. Rosales, Kristin L. Gosselink*

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Chemoarchitecture Of The Lateral Hypothalamic Area: Contiguous Mapping And Distribution Of Six Biomarkers In The Adult Male Rat, Briana E. Pinales^, Nicole Dominguez, Arshad M. Khan*

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Ethanol Reward Conditioning In Drosophila Melanogaster, Isaac A. Moya^, Young-Cho Kim, Kyung-An Han*

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Data Sharing In Neuroimaging Research, Jean-Baptiste Poline, Janis L. Breeze, Satrajit Ghosh, Krzysztof Gorgolewski, Yaroslav O. Halchenko

Dartmouth Scholarship

Significant resources around the world have been invested in neuroimaging studies of brain function and disease. Easier access to this large body of work should have profound impact on research in cognitive neuroscience and psychiatry, leading to advances in the diagnosis and treatment of psychiatric and neurological disease. A trend toward increased sharing of neuroimaging data has emerged in recent years. Nevertheless, a number of barriers continue to impede momentum. Many researchers and institutions remain uncertain about how to share data or lack the tools and expertise to participate in data sharing. The use of electronic data capture (EDC) methods …

Validation On Sodium Channel Dependence By Electrical Stimulation-Induced Dopamine Release, Alice E. Hernandez ^, Mabel N. Terminel, Edward Castaneda *

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Neural Synchrony In The Zebra Finch Brain, Sydney Pia Goings

Scripps Senior Theses

I am interested in discovering the role of field potential oscillations in producing synchrony within the song system of the male zebra finch brain. An important function attributed to neural synchrony is sensorimotor integration. In the production of birdsong, sensorimotor integration is crucial, as auditory feedback is necessary for the maintenance of the song. A cortical-thalamic-cortical feedback loop is thought to play a role in the integration of auditory and motor information for the purpose of producing song. Synchronous activity has been observed between at least two nuclei in this feedback loop, MMAN and HVC. Since low frequency field potential …

Dysregulation Of System Xc- And Its Impact On Cocaine Seeking, Aric Madayag

Dissertations (1934 -)

Abnormal glutamate signaling in the brain, particularly in the nucleus accumbens core, contributes to compulsive cocaine-seeking behavior. In the nucleus accumbens, two distinct pools of glutamate exist. The synaptic pool stimulates excitatory postsynaptic receptors, leading to cocaine seeking. Cystine-glutamate exchange by system xc- contributes to the extrasynaptic pool and regulates neurotransmission by activating extrasynaptic receptors including inhibitory Group II metabotropic glutamate receptors, positioning this as an important mechanism for regulating nucleus accumbens activity. We and others have found decreased levels of cystine-glutamate exchange in animals withdrawn from chronic cocaine administration. In chapter 1, we describe studies directly implicating diminished system …

Cosmetic Neurology: Enhancement Of The Mind And Attention Deficit Hyperactive Disorder Medication Abuse Among College Students, Mary M. Huff

Senior Honors Theses

Cosmetic neurology is becoming increasingly popular, and it is not just sleep deprived, over worked college students who are interested. People are beginning to seek off-label prescriptions for medications that are typically used to treat disorders such as attention deficit hyperactive disorder (ADHD) or narcolepsy, while researchers are trying to create drugs used solely for mind enhancement purposes. Along with these drugs come many legal and ethical quandaries relating to the regulation of current use as well as the what ifs of future possibilities. A survey was conducted among college students regarding the diagnosis of ADHD, the abuse of ADHD …

A Drosophila Deg/Enac Subunit Functions Specifically In Gustatory Neurons Required For Male Courtship Behavior, E. Starostina, T. Liu, V. Vijayan, Zheng Zheng , '11, Kathleen King Siwicki, C. W. Pikielny

Biology Faculty Works

Detection of specific female pheromones stimulates courtship behavior in Drosophila melanogaster males, but the chemosensory molecules, cells, and mechanisms involved remain poorly understood. Here we show that ppk25, a DEG/ENaC ion channel subunit required for normal male response to females, is expressed at highest levels in a single sexually dimorphic gustatory neuron of most taste hairs on legs and wings, but not in neurons that detect courtship-inhibiting pheromones or food. Synaptic inactivation of ppk25-expressing neurons, or knockdown of ppk25 expression in all gustatory neurons, significantly impairs male response to females, whereas gustatory expression of ppk25 rescues the courtship behavior of …

Brainstorm: Of Sign Language And Combat Veterans, Part 2, John J. Medina Ph.D.

Brainstorm

In the last entry I talked about sign language, and I promised in this space to talk about combat veterans. This entry fulfills the promise (though I am also going to talk about business cards).

Integration Of Subthreshold And Suprathreshold Excitatory Barrages Along The Somatodendritic Axis Of Pyramidal Neurons, Hysell V. Oviedo, Alex D. Reyes

Publications and Research

Neurons integrate inputs arriving in different cellular compartments to produce action potentials that are transmitted to other neurons. Because of the voltage- and time-dependent conductances in the dendrites and soma, summation of synaptic inputs is complex. To examine summation of membrane potentials and firing rates, we performed whole-cell recordings from layer 5 cortical pyramidal neurons in acute slices of the rat’s somatosensory cortex. We delivered subthreshold and suprathreshold stimuli at the soma and several sites on the apical dendrite, and injected inputs that mimic synaptic barrages at individual or distributed sites. We found that summation of subthreshold potentials differed from …

Selective Serotonergic Excitation Of Callosal Projection Neurons, Daniel Avesar, Allan T. Gulledge

Dartmouth Scholarship

Serotonin (5-HT) acting as a neurotransmitter in the cerebral cortex is critical for cognitive function, yet how 5-HT regulates information processing in cortical circuits is not well understood. We tested the serotonergic responsiveness of layer 5 pyramidal neurons (L5PNs) in the mouse medial prefrontal cortex (mPFC), and found three distinct response types: long-lasting 5-HT_1A (1A) receptor-dependent inhibitory responses (84% of L5PNs), 5-HT_2A (2A) receptor-dependent excitatory responses (9%), and biphasic responses in which 2A-dependent excitation followed brief inhibition (5%). Relative to 5-HT-inhibited neurons, those excited by 5-HT had physiological properties characteristic of callosal/commissural (COM) neurons that project to the …

Vestibular And Attractor Network Basis Of The Head Direction Cell Signal In Subcortical Circuits, Benjamin J. Clark, Jeffrey S. Taube

Dartmouth Scholarship

Accurate navigation depends on a network of neural systems that encode the moment-to-moment changes in an animal's directional orientation and location in space. Within this navigation system are head direction (HD) cells, which fire persistently when an animal's head is pointed in a particular direction (Sharp et al., 2001a; Taube, 2007). HD cells are widely thought to underlie an animal's sense of spatial orientation, and research over the last 25+ years has revealed that this robust spatial signal is widely distributed across subcortical and cortical limbic areas. The purpose of the present review is to summarize some of …

Brainstorm: Of Sign Language And Combat Veterans, Part 1, John J. Medina Ph.D.

Brainstorm

Dr. McNeill has been researching the relationship between verbal and nonverbal communications for most of his career, a subject we began discussing last entry. His work is very relevant to our ongoing conversation about nature, nurture, and human behavior.

Brainstorm: Nature And Nurture And Dogs, John J. Medina Ph.D.

Brainstorm

It is easy to run across the intersection between nature and nurture in the everyday routines of life. You can even find it in a crisis, as the following true story relates.

A Parametric Investigation Of Pattern Separation Processes In The Medial Temporal Lobe, Sarah E. Motley

Theses and Dissertations

The hippocampus is thought to be involved in memory formation and consolidation, with computational models proposing the process of pattern separation as a means for encoding overlapping memories. Previous research has used semantically related targets and lures to investigate hippocampal responses to mnemonic interference. Here, we attempted to define the response function of the hippocampus and its inputs during pattern separation by parametrically varying target-lure similarity in a continuous recognition task. We also investigated the effect of task demands (intentional versus incidental encoding) on pattern separation processes. We collected functional magnetic resonance imaging (fMRI) data while participants were shown a …

Brainstorm: Of Weirds And Sushis And People Who Use Chopsticks, John J. Medina Ph.D.

Brainstorm

Understanding the contributions that nature and nurture make to a given behavior is tricky business, even for professionals in the field. The research world is littered with heroic, but ultimately unsuccessful, attempts to tease these apart.

Medial Pfc Damage Abolishes The Self-Reference Effect, Carissa Philippi, Melissa Duff, Natalie Denburg, Daniel Tranel, David Rudrauf

Psychology Faculty Works

No abstract provided.