Behavioral Neurobiology Commons^™

The Serotonin 1b Receptor In Psilocybin’S Therapeutic-Like Mechanisms: From Behavior To Network Reorganization, Sixtine Fleury

Dartmouth College Ph.D Dissertations

Mood disorders represent a substantial and growing global health crisis, with ~10 million adults in the US meeting criteria for a major depressive disorder (MDD). Current first-line treatments such as SSRIs require long-term daily administration and fail a significant proportion of patients, driving renewed interest in rapid-acting alternatives. Psilocybin, a serotonergic psychedelic, shows growing clinical evidence of efficacy in treating depressive and anxiety disorders, often producing therapeutic effects persisting weeks to months following a single dose. Yet, the neural mechanisms underlying these enduring effects remain poorly understood and have been largely attributed to the serotonin 2A receptor (5-HT2AR) based on …

Biomarkers That Could Explain Parasite-Induced Behavioral Alterations In The Golden Shiner (Notemigonus Crysoleucas) – Posthodiplostomum System, Laura D. Nicolas

All HCAS Student Capstones, Theses, and Dissertations

Trophically transmitted parasites require an intermediate host to be consumed and often manipulate host phenotype (i.e., morphology, physiology, and/or behavior) to increase predation risk by definitive hosts. Posthodiplostomum is a trematode with a complex life cycle involving snails as first hosts, fish as second intermediate hosts, and piscivorous birds as definitive hosts. In fish hosts, Posthodiplostomum infection has been linked to increased predation, suggesting suppression of antipredator behaviors. However, the specific physiological pathways remained unexplored and changes in the host’s neural, endocrine, and immune systems could be involved. Thus, I examined whether Posthodiplostomum infection intensity was associated with brain serotonin …

Behavioral And Neural Mechanisms Of Serotonin Modulation Of Impulsivity And Reward, Stephanie S. Desrochers

Dartmouth College Ph.D Dissertations

Despite its prevalence in many psychiatric disorders, such as attention deficit hyperactivity disorder, suicidal depression, schizophrenia, and aggression and motivational disorders, impulsivity and its biological bases remain poorly understood. Subdivisions of impulsivity, including impulsive action (reduced response inhibition) and impulsive choice (reduced delay of gratification), sometimes present in an uncorrelated manner. This complexity renders pathological impulsivity difficult to treat, as different underlying causes likely result in different phenotypic presentations, despite being placed under one umbrella term. In order to study the behavior and biology of one particular facet of impulsivity, this dissertation utilizes the serotonin 1B receptor (5-HT1BR; an inhibitory …

Circuits Underlying Serotonin Mediated Sex Differences In Fear Learning, Rebecca Ravenelle

Dissertations, Theses, and Capstone Projects

Post-traumatic stress disorder (PTSD) is a trauma-related disorder characterized by intense fearful memory formation. Women are twice as likely as men to develop PTSD, indicating there may be sex differences in the underlying neural circuits. Given that serotonin (5-HT) dysfunction is implicated in PTSD, and 5-HT modulates fear learning, we investigated whether there are sex differences in the modulation of fear learning by 5-HT. We administered the selective serotonin reuptake inhibitor (SSRI) citalopram (20mg/kg or 10m/kg, i.p.) once to male and female mice prior to auditory fear conditioning and tested the effects on fear memory the next day. We found …

The Development And Evaluation Of Novel Da Transport Inhibitors And Their Effects On Effort-Related Motivation: A Review, Mukund Desibhatla

Honors Scholar Theses

Depression is a debilitating disorder that can cause motivational deficits such as psychomotor retardation, anergia, apathy, and fatigue. Recent research indicates that these motivational deficits, and potential pathways of therapeutic intervention, can be studied in animal models involving rats and mice. Treatments with the VMAT-2 inhibitor tetrabenazine (TBZ) and cytokine interleukin-1ß (IL-1ß) can create a low-effort bias and impair effort-related motivation (Nunes et al. 2013, 2014). A number of high-affinity DA transport inhibitors such as d-amphetamine, methylphenidate, and cocaine can restore extracellular DA, albeit with the cost of undesirable effects such as high abuse liability. These observations have led researchers …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}

Post-Synaptic Mechanisms Of Early And Late Prepulse Inhibition In The Goldfish, Daniel Bronson

Dissertations, Theses, and Capstone Projects

Sensorimotor gating, or prepulse inhibition (PPI), attenuates the startle response during sensory processing by limiting sensory input to the startle circuit. In the goldfish startle circuit, a single action potential in the Mauthner-cell (M-cell) triggers the startle response. PPI in the M-cell is mediated by multiple post-synaptic mechanisms, including the activation of a tonic, shunting inhibition as well as a voltage-sensitive conductance, both of which briefly reduce M-cell excitability. However, the specific channels and pathways that modulate PPI are not fully known. This work further characterizes the post-synaptic conductances that mediate PPI by blocking voltage-gated and inward-rectifying potassium channels, antagonizing …

Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval

Dissertations, Theses, and Capstone Projects

The serotonergic system has been the major candidate in the pathophysiology of mood related disorders such as anxiety and major depressive disorder (MDD). Unfortunately, current antidepressant drugs are ineffective in 50% of the population and require chronic administration for a period of 3-6 weeks before the onset of therapeutic response. 5-HT4 receptor (5-HT₄R) agonists have emerged as potential candidates for fast antidepressant action, since an antidepressant response can be achieved after 3 days of pharmacological administration in rodents.

This dissertation aims to investigate the role of casein kinase 2 (CK2) as a regulator of 5-HT₄R expression …

Characterization Of G-Protein Coupled Receptors In Pain, Depression And Anxiety, Neil Lax

Electronic Theses and Dissertations

Chronic pain and major depressive disorder are widespread conditions in the world. Interestingly, these conditions often occur comorbidly, with each individual disease amplifying the symptoms of the other. A significant amount of preclinical research in pain and depression focuses on G-protein coupled receptors (GPCRs), implying that GPCRs may be useful in treating this comorbidity. Our efforts have sought to characterize several poorly understood GPCRs, including the serotonin receptor subtypes 2C and 7 (5-HT2CR and 5-HT7R) and metabotropic glutamate receptor 5 (mGluR5), along with more well-known GPCRs such as the mu opioid receptor (MOR), and the role that they play in …

A Touchscreen Assay To Probe The Role Of The Serotonergic System In Learning And Visual Information Processing, Jeffrey M. Dorsch, Alexandr Pak, Alexander A. Chubykin

The Summer Undergraduate Research Fellowship (SURF) Symposium

The neurotransmitter serotonin is involved in numerous processes in the brain such as behavior, learning, memory, mood, and neurodevelopment. Serotonin signaling is regulated by the serotonin transporter protein (SERT), which maintains normal serotonin levels. Mutations in the SERT gene are known to correlate with cognitive and behavioral deficits seen in psychiatric disorders, such as anxiety disorders, depression, and autism spectrum disorder. Researchers study these deficits using SERT knockout (KO) mice, a model that lacks functional SERT and displays changes in anxiety, learning, and motivation. We are interested in how the absence of SERT affects visual processing and learning. A popular …

Protein Kinase M Zeta-Mediated Ltp Maintenance In The Non-Human Primate Hippocampus: A Role For Stress And Serotonergic Signaling In Affective Processing, Sasha L. Fulton

Theses and Dissertations

Early-Life Stress (ELS) is associated with vulnerability to mood disorder, but it’s not well understood how ELS contributes to deficits in cognitive function. Atypical PKMzeta is critical for LTP maintenance and memory. The current study aims to characterize the ELS phenotype with respect to this key marker of hippocampal LTP.

Exploring The Relationship Between Behaviour And Neurochemistry In The Polyphenic Spider, Anelosimus Studiosus (Araneae: Theridiidae), Jennifer B. Price

Electronic Theses and Dissertations

The importance of social behaviour is evident in human society, but there are both costs and benefits associated with cooperation and sociality throughout the animal kingdom. At what point do the benefits outweigh the costs, and when do selective pressures favour sociality and colonization over solitude and independence? To investigate these questions, we have focused on an anomalous species of spider, Anelosimus studiosus, also known now as the northern social spider. Throughout its broad range, A. studiosus is solitary and aggressive, but recently, colonies of cooperative and social individuals have been observed at northern latitudes. This leads to two …

Day-Night Differences In Neural Activation In Histaminergic And Serotonergic Areas With Putative Projections To The Cerebrospinal Fluid In A Diurnal Brain, Alexandra Castillo-Ruiz, Andrew J. Gall, Laura Smale, Antonio A. Nunez

Faculty Publications

In nocturnal rodents, brain areas that promote wakefulness have a circadian pattern of neural activation that mirrors the sleep/wake cycle, with more neural activation during the active phase than during the rest phase. To investigate whether differences in temporal patterns of neural activity in wake-promoting regions contribute to differences in daily patterns of wakefulness between nocturnal and diurnal species, we assessed Fos expression patterns in the tuberomammillary (TMM), supramammillary (SUM), and raphe nuclei of male grass rats maintained in a 12:12 h light-dark cycle. Day-night profiles of Fos expression were observed in the ventral and dorsal TMM, in the SUM, …

Serotonin, Motivation, And Playfulness In The Juvenile Rat, Stephen M. Siviy, Loren M. Deron, Chelsea R. Kasten

Psychology Faculty Publications

The effects of the selective 5HT1A agonist 8-OH-DPAT were assessed on the play behavior of juvenile rats. When both rats of the test pair were comparably motivated to play, the only significant effect of 8-OH-DPAT was for play to be reduced at higher doses. When there was a baseline asymmetry in playful solicitation due to a differential motivation to play and only one rat of the pair was treated, low doses of 8-OH-DPAT resulted in a collapse of asymmetry in playful solicitations. It did not matter whether the rat that was treated initially accounted for more nape contacts or fewer …

Neurochemical Levels Correlate With Population Level Differences In Social Structure And Individual Behavior In The Polyphenic Spider, Anelosimus Studiosus., Jennifer Bryson Price

Electronic Theses and Dissertations

Anelosimus studiosus is a socially polyphenic spider. Individuals can be classified as social/tolerant or solitary/aggressive. These behavioral differences are associated with considerable variation in social structure. Here, we begin to examine the physiological differences that may underlie the behavioral dimorphism in this species and possible implications for the evolution of sociality. Octopamine is a neurotransmitter that has been found to elevate aggression in invertebrates. Serotonin has been shown, in some cases, to interact antagonistically with octopamine. We used High Pressure Liquid Chromatography with Electrochemical Detection to quantify levels of these neurochemicals among adult females from social (multi-female) and solitary (single-female) …

The Parallel Worm Tracker: A Platform For Measuring Average Speed And Drug-Induced Paralysis In Nematodes, Daniel Ramot, Brandon E. Johnson, Tommie L. Berry Jr., Lucinda Carnell, Miriam B. Goodman

All Faculty Scholarship for the College of the Sciences

Background

Caenorhabditis elegans locomotion is a simple behavior that has been widely used to dissect genetic components of behavior, synaptic transmission, and muscle function. Many of the paradigms that have been created to study C. elegans locomotion rely on qualitative experimenter observation. Here we report the implementation of an automated tracking system developed to quantify the locomotion of multiple individual worms in parallel.

Methodology/Principal Findings

Our tracking system generates a consistent measurement of locomotion that allows direct comparison of results across experiments and experimenters and provides a standard method to share data between laboratories. The tracker utilizes a video camera …

Bad Nature, Bad Nurture, And Testimony Regarding Maoa And Slc6a4 Genotyping In Murder Trials, Nita A. Farahany, William Bernet, Cindy L. Vnencak-Jones, Stephen A. Montgomery

Faculty Scholarship

Recent research—in which subjects were studied longitudinally from childhood until adulthood—has started to clarify how a child’s environment and genetic makeup interact to create a violent adolescent or adult. For example, male subjects who were born with a particular allele of the monoamine oxidase A gene and also were maltreated as children had a much greater likelihood of manifesting violent antisocial behavior as adolescents and adults. Also, individuals who were born with particular alleles of the serotonin transporter gene and also experienced multiple stressful life events were more likely to manifest serious depression and suicidality. This research raises the question …

Behavioural Genetics In Criminal Cases: Past, Present And Future, Nita A. Farahany, William Bernet

Faculty Scholarship

Researchers studying human behavioral genetics have made significant scientific progress in enhancing our understanding of the relative contributions of genetics and the environment in observed variations in human behavior. Quickly outpacing the advances in the science are its applications in the criminal justice system. Already, human behavioral genetics research has been introduced in the U.S. criminal justice system, and its use will only become more prevalent. This essay discusses the recent historical use of behavioral genetics in criminal cases, recent advances in two gene variants of particular interest in the criminal law, MAOA and SLC6A4, the recent expert testimony on …

Mechanism Of Triazolo-Benzodiazepine And Benzodiazepine Action In Anxiety And Depression: Behavioral Studies With Concomitant In Vivo Ca1 Hippocampal Norepinephrine And Serotonin Release Detection In The Behaving Animal, Patricia A. Broderick, Omotola Hope, Pierrot Jeannot

Publications and Research

1. Real time, in vivo microvoltammetric studies were performed, using miniature carbon-based sensors, to concurrently detect norepinephrine (NE) release and serotonin (5-HT) release, in 2 separate electrochemical signals, within CA₁ region of hippocampus in the freely moving and behaving, male, Sprague Dawley laboratory rat.

2. Concurrently, four parameters of open-field Behavior I.E. Ambulations, Rearing, Fine Movements and Central Ambulatory behavior (a measure of anxiety reduction behavior), were assayed by infrared photobeam detection.

3. Time course studies showed that the mechanism of action of the triazolobenzodiazepine (TBZD), adinazolam, (Deracyn®) is dramatically different from that of the classical benzodiazepine (BZD), diazepam …