Neuroscience and Neurobiology Commons^™

Controlling Feeding Behavior By Chemical Or Gene-Directed Targeting In The Brain: What’S So Spatial About Our Methods?, Arshad Khan

Arshad M. Khan, Ph.D.

Intracranial chemical injection (ICI) methods have been used to identify the locations in the brain where feeding behavior can be controlled acutely. Scientists conducting ICI studies often document their injection site locations, thereby leaving kernels of valuable location data for others to use to further characterize feeding control circuits. Unfortunately, this rich dataset has not yet been formally contextualized with other published neuroanatomical data. In particular, axonal tracing studies have delineated several neural circuits originating in the same areas where ICI injection feeding-control sites have been documented, but it remains unclear whether these circuits participate in feeding control. However, comparing …

Progressive Levels Of Physical Dependence To Tobacco Coincide With Changes In The Anterior Cingulum Bundle Microstructure, Wei Huang, Joseph R. Difranza, David N. Kennedy, Nanyin Zhang, Douglas M. Ziedonis, W. W. Sanouri A. Ursprung, Jean A. King

Douglas M. Ziedonis

BACKGROUND: The tobacco withdrawal syndrome indicates the development of neurophysiologic dependence. Clinical evidence indicates that neurophysiologic dependence develops through a set sequence of symptom presentation that can be assessed with a new 3-item survey measure of wanting, craving, and needing tobacco, the Level of Physical Dependence (PD). This study sought to determine if advancing neurophysiologic dependence as measured by the Level of PD correlates with characteristics of white matter structure measured by Fractional Anisotropy (FA).

METHODS: Diffusion-MRI based FA and diffusion tensor imaging probabilistic tractography were used to evaluate 11 smokers and 10 nonsmokers. FA was also examined in relation …

Moral Dilemma Judgment Revisited: A Loreta Analysis, Armando F. Rocha, Fábiot T. Rocha, Eduardo Massad

Armando F Rocha

Recent neuroscience investigations on moral judgment have provided useful information about how brain processes such complex decision making. All these studies so were fMRI investigations and therefore constrained by the poor resolution of this technique. Recent advances in electroencephalography (EEG) analysis provided by Low Resolution Tomogray (Loreta), Principal Component (PCA), Correlation and Regression Analysis improved EEG spatial resolution and make EEG a very useful technique in decision-making studies. Here, we reinvestigate previously fMRI study of personal (PD) and impersonal (ID) moral dilemma judgment, taking profit of these new EEG analysis improvements. Compared to the previous fMRI results, Loreta and PCA …

Synaptic And Systems Memory Consolidation In The Black-Capped Chickadee (Poecile Atricapillus), Matthew Barrett

Matthew J. Barrett

ABSTRACT Memory consolidation - the time-dependent stabilization of information- involves two processes: 1) synaptic consolidation and 2) systems consolidation. Synaptic consolidation uses a series of protein synthesis cascades that make lasting changes in the underlying neural architecture of a memory. Systems consolidation involves the reorganization of memory such that, with the passage of time, memory that is initially hippocampus-dependent can be retrieved and activated independent of the hippocampus. Black-capped chickadees (Poecile atricapillus) store and relocate food using hippocampus-dependent spatial memory. In Chapter 2 inhibition of protein synthesis by anisomycin, either 0 and 2 h or 4 and 6 h after …

Prolactin And Fmri Response To Skf38393 In The Baboon, Brad D. Miller, Lauren A. Marks, Jonathan M. Koller, Blake J. Newman, G Larry Bretthorst, Kevin J. Black

Kevin J. Black, MD

Background: This study’s goal was to provide dose-response data for a dopamine agonist in the baboon using standard methods (replicate measurements at each dose, across a range of doses), as a standard against which to subsequently validate a novel pharmacological MRI (phMRI) method. Dependent variables were functional MRI (fMRI) data from brain regions selected a priori, and systemic prolactin release. Necessary first steps included estimating the magnitude and time course of prolactin response to anesthesia alone and to various doses of agonist. These first steps (“time course studies”) were performed with three agonists, and the results were used to select …

Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass

Aaron P Blaisdell

Welcome to the first issue of the Journal of Evolution and Health! The Journal of Evolution and Health is the peer-reviewed, open-access journal of the Ancestral Health Society, a community of scientists, healthcare professionals, and laypersons who collaborate to understand health challenges from an evolutionary perspective.

Identifying Links In The Chain: The Dynamic Coupling Of Catecholamines, Peptide Synthesis, And Peptide Release In Hypothalamic Neuroendocrine Neurons, Alan Watts, Arshad Khan

Arshad M. Khan, Ph.D.

Compared to conventional neurons that use synaptic mechanisms to communicate with closely apposed targets, peptidergic neuroendocrine neurons release relatively large quantities of peptide into the vasculature to control neuroendocrine function at more distal sites. This means that maintaining adequate amounts of peptide for release through controlled biosynthesis is critical for their function. But the flexible and adaptive responses these neurons generate to many different challenges require synthesis and release must be coordinated in some way. How neuroendocrine—or in fact, any neuropeptide—neurons link appropriate levels of peptide biosynthesis with the patterns of action potentials that drive peptide release is unknown. Here …

Inwardly Rectifying Potassium Channels In Drosophila, Zhuo Luan, Hong-Sheng Li

zhuo luan

Inwardly rectifying potassium channels (Kir) are a special subset of potassium selective ion channels which pass potassium more easily into rather than out of the cell. These channels mediate a variety of cellular functions, including control of membrane resting potential, maintenance of potassium homeostasis and regulation of cellular metabolism. Given the existence of fifteen Kir genes in mammals, current genetic studies using mutant animals that lack a single channel may have missed many important physiological functions of these channels due to gene redundancy. This issue can be circumvented by using a simple model organism like Drosophila, whose genome encodes only …

Issues Related To Development Of New Antiseizure Treatments, Karen S. Wilcox, Tracy Dixon-Salazar, Graeme J. Sills, Elinor Ben-Menachem, H. Steve White, Roger J. Porter, Marc A. Dichter, Solomon L. Moshe, Jeffrey L. Noebels, Michael D. Privitera, Michael A. Rogawski

Michael A. Rogawski

This report represents a summary of the discussions led by the antiseizure treatment working group of the International League Against Epilepsy (ILAE)/American Epilepsy Society (AES) Working Groups joint meeting in London (London Meeting). We review here what is currently known about the pharmacologic characteristics of current models of refractory seizures, both for adult and pediatric epilepsy. In addition, we address how the National Institute of Neurological Disorders and Stroke (NINDS)-funded Anticonvulsant Screening Program (ASP) is evolving to incorporate appropriate animal models in the search for molecules that might be sufficiently novel to warrant further pharmacologic development. We also briefly address …

Enhanced Nicotine Self-Administration And Suppressed Dopaminergic Systems In A Rat Model Of Diabetes, Laura O'Dell

Laura Elena O'Dell

Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water. In order to examine the contribution of dopamine to our behavioral effects, dopamine transporter (DAT), D1 and D2 receptor levels were compared …

Alcohol-Induced Il-1beta In The Brain Is Mediated By Nlrp3/Asc Inflammasome Activation That Amplifies Neuroinflammation, Dora Lippai, Shashi Bala, Jan Petrasek, Timea Csak, Ivan Levin, Evelyn Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Alcohol-induced neuroinflammation is mediated by proinflammatory cytokines, including IL-1beta. IL-1beta production requires caspase-1 activation by inflammasomes-multiprotein complexes that are assembled in response to danger signals. We hypothesized that alcohol-induced inflammasome activation contributes to increased IL-1beta in the brain. WT and TLR4-, NLRP3-, and ASC-deficient (KO) mice received an ethanol-containing or isocaloric control diet for 5 weeks, and some received the rIL-1ra, anakinra, or saline treatment. Inflammasome activation, proinflammatory cytokines, endotoxin, and HMGB1 were measured in the cerebellum. Expression of inflammasome components (NLRP1, NLRP3, ASC) and proinflammatory cytokines (TNF-alpha, MCP-1) was increased in brains of alcohol-fed compared with control mice. Increased …

A Mechanistic Hypothesis Of The Factors That Enhance Vulnerability To Nicotine Use In Females, Laura O'Dell

Laura Elena O'Dell

Women are particularly more vulnerable to tobacco use than men. This review proposes a unifying hypothesis that females experience greater rewarding effects of nicotine and more intense stress produced by withdrawal than males. We also provide a neural framework whereby estrogen promotes greater rewarding effects of nicotine in females via enhanced dopamine release in the nucleus accumbens (NAcc). During withdrawal, we suggest that corticotropin-releasing factor (CRF) stress systems are sensitized and promote a greater suppression of dopamine release in the NAcc of females versus males. Taken together, females display enhanced nicotine reward via estrogen and amplified effects of withdrawal via …

Genetics In Non-Genetic Model Systems, Carlos Lois, James Groves

Carlos Lois

The past few decades have seen the field of genetic engineering evolve at a rapid pace, with neuroscientists now equipped with a wide range of tools for the manipulation of an animal's genome in order to study brain function. However, the number of species to which these technologies have been applied, namely the fruit fly, C. elegans, zebrafish and mouse, remains relatively few. This review will discuss the variety of approaches to genetic modification that have been developed in such traditional 'genetic systems', and highlight the progress that has been made to translate these technologies to alternative species such as …

Wandering Neuronal Migration In The Postnatal Vertebrate Forebrain, Benjamin Scott, Timothy Gardner, Ni Ji, Michale Fee, Carlos Lois

Carlos Lois

Most non-mammalian vertebrate species add new neurons to existing brain circuits throughout life, a process thought to be essential for tissue maintenance, repair, and learning. How these new neurons migrate through the mature brain and which cues trigger their integration within a functioning circuit is not known. To address these questions, we used two-photon microscopy to image the addition of genetically labeled newly generated neurons into the brain of juvenile zebra finches. Time-lapse in vivo imaging revealed that the majority of migratory new neurons exhibited a multipolar morphology and moved in a nonlinear manner for hundreds of micrometers. Young neurons …

Genetic Labeling Of Neuronal Subsets Through Enhancer Trapping In Mice, Wolfgang Kelsch, Alberto Stolfi, Carlos Lois

Carlos Lois

The ability to label, visualize, and manipulate subsets of neurons is critical for elucidating the structure and function of individual cell types in the brain. Enhancer trapping has proved extremely useful for the genetic manipulation of selective cell types in Drosophila. We have developed an enhancer trap strategy in mammals by generating transgenic mice with lentiviral vectors carrying single-copy enhancer-detector probes encoding either the marker gene lacZ or Cre recombinase. This transgenic strategy allowed us to genetically identify a wide variety of neuronal subpopulations in distinct brain regions. Enhancer detection by lentiviral transgenesis could thus provide a complementary method for …

Similarity Of Visual Selectivity Among Clonally Related Neurons In Visual Cortex, Gen Ohtsuki, Megumi Nishiyama, Takashi Yoshida, Tomonari Murakami, Mark Histed, Carlos Lois, Kenichi Ohki

Carlos Lois

Neurons in rodent visual cortex are organized in a salt-and-pepper fashion for orientation selectivity, but it is still unknown how this functional architecture develops. A recent study reported that the progeny of single cortical progenitor cells are preferentially connected in the postnatal cortex. If these neurons acquire similar selectivity through their connections, a salt-and-pepper organization may be generated, because neurons derived from different progenitors are intermingled in rodents. Here we investigated whether clonally related cells have similar preferred orientation by using a transgenic mouse, which labels all the progeny of single cortical progenitor cells. We found that preferred orientations of …

Increasing Heterogeneity In The Organization Of Synaptic Inputs Of Mature Olfactory Bulb Neurons Generated In Newborn Rats, Wolfgang Kelsch, Shuyin Sim, Carlos Lois

Carlos Lois

New neurons are added into the mammalian olfactory bulb throughout life, but it remains unknown whether the properties of new neurons generated in newborn animals differ from those added during adulthood. We compared the densities of glutamatergic synapses of granule cells (GCs) generated in newborn and adult rats over extended periods of time. We observed that, whereas adult-born GCs maintained stable cell-to-cell variability of synaptic densities soon after they integrated into the circuit, cell-to-cell variability of synaptic densities of neonatal-born GCs increased months after their integration. We also investigated whether the synaptic reorganization induced by sensory deprivation occurred differently in …

Coincident Generation Of Pyramidal Neurons And Protoplasmic Astrocytes In Neocortical Columns, Sanjay Magavi, Drew Friedmann, Garrett Banks, Alberto Stolfi, Carlos Lois

Carlos Lois

Astrocytes, one of the most common cell types in the brain, are essential for processes ranging from neural development through potassium homeostasis to synaptic plasticity. Surprisingly, the developmental origins of astrocytes in the neocortex are still controversial. To investigate the patterns of astrocyte development in the neocortex we examined cortical development in a transgenic mouse in which a random, sparse subset of neural progenitors undergoes CRE/lox recombination, permanently labeling their progeny. We demonstrate that neural progenitors in neocortex generate discrete columnar structures that contain both projection neurons and protoplasmic astrocytes. Ninety-five percent of developmental cortical columns labeled in our system …

Behavioral, Biochemical, And Molecular Indices Of Stress Are Enhanced In Female Versus Male Rats Experiencing Nicotine Withdrawal, Laura O'Dell

Laura Elena O'Dell

Stress is a major factor that promotes tobacco use and relapse during withdrawal. Although women are more vulnerable to tobacco use than men, the manner in which stress contributes to tobacco use in women versus men is unclear.Thus, the goal of this study was to compare behavioral and biological indices of stress in male and female rats during nicotine withdrawal. Since the effects of nicotine withdrawal are age-dependent, this study also included adolescent rats. An initial study was conducted to provide comparable nicotine doses across age and sex during nicotine exposure and withdrawal. Rats received sham surgery or an osmotic …

Effects On Pharmacological Properties Of Chimeric Α6Β2Β3* Achrs With Α3 Cytoplasmic Domain(S) And The Ml (Methionine To Leucine) Mutation At Position 211 Of Α6, Carson K. Ley

Carson K Ley

α6β2β3* acetylcholine receptors (AChRs) on dopaminergic neurons located in the brain are critical targets for drugs to treat nicotine addiction and Parkinson's disease. a6 and a3 are acetylcholine receptor (AChR) subunits closely related in sequence. a3 assembles efficiently with b2 subunits to form functional AChRs in Xenopus laevis oocytes, but a6 does not, presumably because specific chaperones needed for efficient expression are missing (Gotti et al., 2010). Chimeras of a6 with a3 assemble efficiently to form functional AChRs . To be useful and not misleading, it is vital that the chimeras incorporate only enough a3 sequence to insure efficient assembly …

Optogenetic Manipulation Of Neural Activity In Freely Moving Caenorhabditis Elegans, Andrew Leifer, Christopher Fang-Yen, Marc Gershow, Mark Alkema, Aravinthan Samuel

Christopher Fang-Yen

We present an optogenetic illumination system capable of real-time light delivery with high spatial resolution to specified targets in freely moving Caenorhabditis elegans. A tracking microscope records the motion of an unrestrained worm expressing channelrhodopsin-2 or halorhodopsin in specific cell types. Image processing software analyzes the worm's position in each video frame, rapidly estimates the locations of targeted cells and instructs a digital micromirror device to illuminate targeted cells with laser light of the appropriate wavelengths to stimulate or inhibit activity. Because each cell in an unrestrained worm is a rapidly moving target, our system operates at high speed ( …

Human-Specific Histone Methylation Signatures At Transcription Start Sites In Prefrontal Neurons, Hennady Shulha, Jessica Crisci, Denis Reshetov, Jogender Tushir, Iris Cheung, Rahul Bharadwaj, Hsin-Jung Chou, Isaac Houston, Cyril Peter, Amanda Mitchell, Wei-Dong Yao, Richard Myers, Jiang-Fan Chen, Todd Preuss, Evgeny Rogaev, Jeffrey Jensen, Zhiping Weng, Schahram Akbarian

Hsin-Jung Chou

Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes, but little is known about the role of cis-regulatory changes affecting transcription start sites (TSS). Here, we mapped in human, chimpanzee, and macaque prefrontal cortex the genome-wide distribution of histone H3 trimethylated at lysine 4 (H3K4me3), an epigenetic mark sharply regulated at TSS, and identified 471 sequences with human-specific enrichment or depletion. Among these were 33 loci selectively methylated in neuronal but not non-neuronal chromatin from children and adults, including TSS at DPP10 (2q14.1), CNTN4 and CHL1 (3p26.3), and other neuropsychiatric susceptibility …

The United States Undergraduate Neuroscience Curriculum: Neuroscience And Study Abroad, Eric Wiertelak

Eric Wiertelak

No abstract provided.

Developmental Increase In 3h-Muscimol Binding To The Γ-Aminobutyric Acida Receptor In Hypothalamic And Limbic Areas Of The Rat: Why Is The Ventromedial Nucleus Of The Hypothalamus An Exception?, Aline Davis, Margaret Mccarthy

Aline Davis

Using in vitro autoradiography to measure binding of the γ-aminobutyric acidA (GABAA) receptor agonist, muscimol, we examined male and female rats on postnatal days 1, 5, 10, and 20. There were no sex differences in muscimol binding in any hypothalamic or limbic regions examined. However, all regions exhibited a developmental increase in the density of binding, except the ventromedial nucleus (VMN) of the hypothalamus. We have previously shown that the adult VMN is the only hypothalamic nucleus containing an abundance of the α2 subunit of the GABAA receptor and lack of the α1 subunit. We hypothesize that the lack of …

Loss Of Steroidogenic Factor 1 Alters Cellular Topography In The Mouse Ventromedial Nucleus Of The Hypothalamus, Aline Davis, Marianne Seney, Nancy Stallings, Liping Zhao, Keith Parker, Stuart Tobet

Aline Davis

Knockout (KO) mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF-1) exhibit marked structural abnormalities of the ventromedial nucleus of the hypothalamus (VMH). In this study, we sought to determine the molecular mechanisms underlying the VMH abnormalities. To trace SF-1-expressing neurons, we used a SF-1/enhanced green fluorescent protein (eGFP) transgene. Although the total numbers of eGFP-positive cells in wild-type (WT) and SF-1 KO mice were indistinguishable, cells that normally localize precisely within the VMH were scattered more diffusely in adjacent regions in SF-1 KO mice. This abnormal distribution is likely due to the loss of SF-1 expression in VMH …

Human-Specific Histone Methylation Signatures At Transcription Start Sites In Prefrontal Neurons, Hennady P. Shulha, Jessica L. Crisci, Denis Reshetov, Jogender S. Tushir, Iris Cheung, Rahul Bharadwaj, Hsin-Jung Chou, Isaac B. Houston, Cyril J. Peter, Amanda C. Mitchell, Wei-Dong Yao, Richard H. Myers, Jiang-Fan Chen, Todd M. Preuss, Evgeny I. Rogaev, Jeffrey D. Jensen, Zhiping Weng, Schahram Akbarian

Jessica L Crisci

Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes, but little is known about the role of cis-regulatory changes affecting transcription start sites (TSS). Here, we mapped in human, chimpanzee, and macaque prefrontal cortex the genome-wide distribution of histone H3 trimethylated at lysine 4 (H3K4me3), an epigenetic mark sharply regulated at TSS, and identified 471 sequences with human-specific enrichment or depletion. Among these were 33 loci selectively methylated in neuronal but not non-neuronal chromatin from children and adults, including TSS at DPP10 (2q14.1), CNTN4 and CHL1 (3p26.3), and other neuropsychiatric susceptibility …

Breaking Down The Walls Between Neuroscience And Religious Ethics, Harlan Stelmach, Mohammed El Majdoubi

Harlan Stelmach

The Rat Formalin Nociception Assay: Examination Of Putative Analgesic Effects Of Traditional Medicines Yan Hu Suo, Wei Ling Xian, San Qi, And Xu Duan, Eric Wiertelak, E. Gaidis

Eric Wiertelak

No abstract provided.

The Intrinsic Severity Hypothesis Of Pharmacoresistance To Antiepileptic Drugs, Michael Rogawski

Michael A. Rogawski

Pharmacoresistance to antiepileptic drugs (AEDs) is a barrier to seizure freedom for many persons with epilepsy. For nearly two decades, pharmacoresistance has been framed in terms of factors affecting the access of AEDs to their molecular targets in the brain or the actions of the drugs on these targets. Shortcomings in this prevailing view led to the formulation of the intrinsic severity hypothesis of pharmacoresistance to AEDs, which is based on the recognition that there are neurobiologic factors that confer phenotypic variation among individuals with etiologically similar forms of epilepsy and postulates that more severe epilepsy is more difficult to …

Nu Rho Psi, The National Honor Society In Neuroscience, L. Achor, A. Mickley, Eric Wiertelak

Eric Wiertelak

No abstract provided.