Behavioral Neurobiology Commons^™

Investigating The Role Of Cortical Inhibition In Tinnitus, Krystal Beh

Electronic Thesis and Dissertation Repository

Subjective tinnitus is characterized as the perception of a phantom sound with no external acoustic source, and is often described as a “ringing in the ears” sensation. While evidence supports a central origin for tinnitus, the underlying neural mechanisms for this condition remain elusive. The studies presented in this thesis offer significant contributions to understanding the neural basis of tinnitus by (1) validating a behavioural paradigm that can successfully screen rats for transient noise-induced tinnitus without any indications of false-positives, and (2) demonstrating that a local loss of inhibition is sufficient to induce gain enhancement in the primary auditory cortex, …

Tracking Behavioural And Neuronal Responses To Social Pheromones: Insights From A Drosophila Model, Justin R. Croft

Electronic Thesis and Dissertation Repository

If eusociality evolved through modification of pre-social mechanisms for regulating personal reproduction, then even insects like Drosophila may be vulnerable to latent effects of 'queen' pheromone. Here, I test if male fruit flies respond to a eusocial queen bee pheromone. I found that male flies were attracted to queen bee pheromone, and pheromone-treated males raised the intensity of their courting towards conspecific females. These novel observations from Drosophila suggest that male flies have the capacity to respond to queen pheromone in a manner that is comparable to the native response from male (drone) bees. I therefore optimized a nuclear factor …

The Influence Of Estrogen On Sex Differences In Chemotherapy-Induced Nausea And Vomiting (Cinv), Danna L. Zevy

Electronic Thesis and Dissertation Repository

Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing events that affects the quality of life of cancer patients. Evidence suggests that females are more susceptible to CINV than males, but the mechanism remains unknown. The current thesis examined whether higher levels of circulating estrogens in females contributes to this sex difference. CINV was analyzed in a pediatric oncology population, where it was revealed female patients demonstrate increased delayed CINV relative to male patients, in the post-pubertal age group. CINV was also studied by examining the influence of the estrous cycle on anticipatory nausea (AN) in rats. This …

The Effect Of Age On Social Behaviour In Drosophila Melanogaster And The Progeny Of Aged Parents, Dova Brenman

Electronic Thesis and Dissertation Repository

Recent studies have linked neuropsychiatric disorders to older parents. These disorders often include changes in social behaviours like the social spacing between neighbouring individuals, which can be modeled in organisms such as Drosophila melanogaster. I investigated the effects of aging on the social space between neighbouring D. melanogaster and how aging impacts the next generation. To achieve this, I used the social space assay and found that individuals become less social with age and that this effect is passed on to the first generation only. Additionally, accelerating the physiological process of aging via increased rearing temperatures or exposure to …

The Role Of Cholinergic Neurotransmission In Sensory Filtering And Sensorimotor Gating, Erin Azzopardi

Electronic Thesis and Dissertation Repository

At every moment, our brain is bombarded with sensory information. How we filter and process sensory information is critical for daily functioning and cognition. Examples of sensory filtering include habituation (a progressive decrease in responding) and prepulse inhibition (PPI, gating of responding). Our aim is to understand the differential role acetylcholine (ACh) plays in these processes.

To study this we used both reflexive (acoustic startle response: ASR) and non-reflexive (locomotor) behaviours. PPI is hypothesized to occur via inhibitory cholinergic projections from the Pedunculopontine Tegmental Nucleus (PPT) to the startle pathway. The role of ACh in habituation of reflexive and non-reflexive …

The Role Of Forebrain Cholinergic Signalling In Regulating Hippocampal Function And Neuropathology, Mohammed Al-Onaizi

Electronic Thesis and Dissertation Repository

Cholinergic dysfunction has been associated with cognitive abnormalities in a variety of neurodegenerative and neuropsychiatric disorders, including Alzheimer’s Disease (AD). Cumulative use of drugs with anticholinergic activity is associated with increased risk for dementia and AD. Also, cholinergic function has been implicated in predicting the development of key neuropathological hallmarks seen in AD. However, the relationship between cholinergic dysfunction and conservation of cognitive ability as well as neuronal cell maintenance is not fully understood. Here, we tested how information processing and distinct molecular mechanisms associated with AD are regulated by cholinergic tone in genetically-modified mice in which cholinergic transmission was …

Cannabinoid Cb1 Transmission In The Mesolimbic Reward Pathway, Tasha Ahmad

Electronic Thesis and Dissertation Repository

Cannabinoid CB1 receptor (CB1R) transmission within the mesocorticolimbic system plays an important role in forming associative memories, and processing both positive and negative experiences. Opiates generally produce potent rewarding effects and previous evidence suggests that CB1 transmission may modulate the neural reward circuitry involved in opiate reward processing. The ventral tegmental area (VTA), medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and Nucleus Accumbens (NA) are all implicated in opiate-reward processing, contain high levels of CB1 receptors, and are all modulated by dopamine (DA). Although, CB1 transmission within these areas has been heavily implicated in associative memory and learning, the potential …

Developmental Stress And The Effects On Physiological And Cognitive-Behavioural Traits In European Starlings, Tara M. Farrell

Electronic Thesis and Dissertation Repository

Birdsong is a complex, learned vocalization that is a phenotypic expression of male quality. The developmental stress hypothesis describes how the cost to possessing a high quality song is paid in early development. Stressful early-life experiences have adverse effects on the development of the neural circuitry that regulates song learning and production, which results in a male advertising with a low quality song in adulthood. The purpose of this thesis was to test the developmental stress hypothesis in several respects in European starlings (Sturnus vulgaris). My objectives were to assess the long-term effects of developmental stress on (1) …

Neural And Behavioural Responses To Rewards And Losses In Early Development: A Functional Magnetic Resonance Imaging Study, Niki Hosseini-Kamkar

Electronic Thesis and Dissertation Repository

Functional magnetic resonance imaging (fMRI) was used to investigate the neural and behavioural correlates of learning from rewards and losses in children. Greater blood-oxygen-level dependent (BOLD) responses in the ventral striatum (VS) and the ventromedial prefrontal cortex (VMPFC) were found when participants received rewards compared to when they missed out on an opportunity to receive rewards. In contrast, greater BOLD responses in the anterior insula (AI) and the anterior cingulate cortex (ACC) were found when participants received losses compared to when they avoided losing. The BOLD response to rewards in the VS and VMPFC correlated positively with the tendency to …

Contribution Of The Dorsolateral Prefrontal Cortex To Attentional And Mnemonic Processes In Visual Search, Brandon Belbeck

Electronic Thesis and Dissertation Repository

A key characteristic of selective visual attention is that it may be deployed on the basis of our knowledge or goals of the task at hand. Here, we used cryogenic deactivation to investigate the contribution of the dorsolateral PFC to cognitive flexibility and working memory, as well as their relation to the deployment of attention. Macaque monkeys performed visual search tasks requiring them to foveate a target in an array of stimuli. These included a feature search, a constant-target conjunction search, a variable-target search and variable-target with delay search task, with each being more cognitively demanding than the last. Bilateral …

Abnormal Hippocampal Activation In Freely Behaving Mice Deficient For The Vesicular Acetylcholine Transporter, Shahin Moallem

Electronic Thesis and Dissertation Repository

Acetylcholine (Ach) has a fundamental role in cortical activation. The activation of the hippocampus, a cortex implicated in cognitive and sensorimotor functions, is characterized by an increase in power and frequency of oscillations in the theta (4-10 Hz) and gamma (30-100 Hz) frequency range. We studied hippocampal activation in two mutant mouse lines with deficiency in cholinergic functionality: VAChT KD^HET (HET), and VAChT^{Nkx2.1-Cre-flox/flox} (KO). We hypothesized that the mutant mice, relative to wild-type (WT) mice, will manifest abnormal theta and gamma oscillations during different behaviors, and in response to muscarinic cholinergic antagonist scopolamine hydrochloride and to the NMDA …

Dissociating The Psychoactive Effects Of Distinct Cannabis Compounds In The Mesocorticolimbic Circuitry, Jordan S. Zunder

Electronic Thesis and Dissertation Repository

The discovery of the endocannabinoid system propelled understanding of the mechanisms of action of cannabinoid compounds. While marijuana is the most widely used illicit substance in the world, the neuropsychopharmacological mechanisms that underlie the diffuse effects of cannabis in the brain remain poorly understood. This is because marijuana smoke represents a complex mixture of chemical components, possessing dissociable psychoactive properties. Clinical evidence suggests a functional dissociation between the two main pharmacological components of cannabis, Δ9- tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Using a combination of cortical microinfusions during two emotional learning paradigms, and single-unit in vivo electrophysiological recording, we investigated the …

Investigating The Multiple Hit Hypothesis Of Parkinson Disease Using Transgenic Lrrk2-R1441g Rats, Komal T. Shaikh

Electronic Thesis and Dissertation Repository

The ‘multiple hit’ hypothesis of Parkinson disease (PD) suggests that the combination of several risk factors leads to the development of PD. Here, we explore the interaction between two potential causes of PD; a genetic mutation in the leucine-rich repeat kinase 2 (LRRK2) gene and exposure to the neurotoxin, Paraquat. This project characterizes transgenic BAC rats expressing human LRRK2 bearing the familial PD mutation, R1441G. These rats were tested for PD-related deficits at 3, 6, 9 & 12 months. These rats were then exposed to intraperitoneal injections of Paraquat. We hypothesized that LRRK2^R1441G rats will show increased vulnerability …

Understanding The Role Of Cholinergic Tone In The Pedunculopontine Tegmental Nucleus, Kaie Rosborough

Electronic Thesis and Dissertation Repository

Genetically modified mice targeting the vesicular acetylcholine transporter (VAChT) gene have been used as a tool to better understand the role of ACh signaling in specific regions of the brain (Prado et al., 2006; Guzman et al., 2011; de Castro et al., 2009). VAChT stores acetylcholine (ACh) in synaptic vesicles, and changes in this transporter expression directly interferes with ACh release. Here, we use a mouse line with VAChT deletion in the pedunculopontine tegmental nucleus (PPT) to evaluate the consequences of decreased cholinergic signaling from the PPT in vivo. Based on the efferent connectivity from the PPT, our hypothesis is …

Associations Between Hypothalamic-Pituitary-Adrenal Axis System Gene Variants And Cortisol Reactivity In Preschoolers: Main Effects And Gene-Environment Interactions, Haroon I. Sheikh

Electronic Thesis and Dissertation Repository

Exposure to stressful events during early development has consistently been shown to produce long lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis, which may increase vulnerability to mood and anxiety disorders. Recently reported genetic association studies indicate that these disorders may be influenced, in part, by gene-environment interactions (GxE) involving polymorphisms within the corticotrophin-releasing hormone and monoaminergic system genes. However, little is known about how genetic variants and life stress work to shape children’s neuroendocrine reactivity and emerging symptoms. Therefore, the aim of this thesis is to examine main effects of candidate genes and GxE on the neuroendocrine stress response and …

Reaching For The Light: The Prioritization Of Conspicuous Visual Stimuli For Reflexive Target-Directed Reaching, Daniel K. Wood

Electronic Thesis and Dissertation Repository

The degree to which something stands out against the background of its environment communicates important information. The phenomenon of camouflage is a testament of the degree to which visual salience and probability of survival tend to overlap. Salient stimuli often elicit fast, reflexive movements in order to catch prey or avoid a predator. The overarching goal of the work presented in this thesis is to investigate how the physical salience of visual stimuli influence the programming and execution of reaching movements. I approached this question by recording kinematics and muscle responses during reaching movements. Broadly, this thesis investigates the effect …

Contribution Of Trpm2 To Memory Loss In An Alzheimer's Mouse Model, Megan M. Chen

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the progressive deterioration of memory and other intellectual abilities. Accumulation of amyloid-β (Aβ) peptide, the major contributor to the senile plaques central to AD, is thought to mediate neurotoxicity by inducing oxidative stress and calcium dysregulation. Transient Receptor Potential Melastatin type 2 (TRPM2) is a calcium permeable, non-selective cation channel activated under oxidative stress and ultimately induces cell death. The APPSWE/PSEN1ΔE9 double transgenic mouse model carries the human APPswe (Swedish mutations K594N/M595L) and PS1 mutations with a deletion in exon 9 (PS1-dE9), and is one of the most commonly used AD …

Dopamine Modulation Of Emotional Learning In The Medial Prefrontal Cortex, Nicole M. Lauzon

Electronic Thesis and Dissertation Repository

Dopamine (DA) transmission plays a critical role in the processing of emotionally salient information and in associative learning and memory processes. Within the mammalian brain, neurons within the medial prefrontal cortex (mPFC) are involved critically in the encoding, expression, and extinction of emotionally salient learned information. Within the mPFC, DAergic transmission is involved importantly in controlling attention related and motivational processes, particularly within the context of emotionally salient sensory information. Considerable evidence suggests differential roles for DA D₁-like versus D₂-like receptors, including the D₄-receptor subtype, in the regulation of neuronal activity and emotional processing …

Exploring The Neural Basis Of Top-Down Guided Action In Macaque Monkeys, Jessica M. Phillips

Electronic Thesis and Dissertation Repository

To thoroughly characterize any brain mechanism requires an appropriate animal model for invasive studies. An invaluable model system used toward a comprehension of cognitive neurophysiology is the macaque monkey. It is important to delineate similarities and limitations for this model in relation to the human brain and cognition. In this thesis, we have thus conducted three experiments to investigate putative generalizations between monkeys and humans regarding the neural processes associated with top-down action control in monkeys.

Our daily behaviour is largely comprised of automatic routine actions. The frequent repetition of certain behaviours in response to particular contexts can give rise …

Circadian Rhythms In Reward And Underlying Neural Circuits, Ricardo M. Baltazar

Electronic Thesis and Dissertation Repository

Studies suggest that the circadian timing system exerts an important influence on responses to rewarding stimuli. Diurnal rhythms in the rewarding value of amphetamine and mating behavior were observed, but differed in the pattern of their timing. Daily fluctuations in reward were correlated with oscillations in mesolimbic dopaminergic activity in both the nucleus accumbens (NAc) and ventral tegmental area (VTA), with a peak in NAc coinciding with the peak of sex reward, while the peak in the VTA associated with the peak in amphetamine reward. Also, rhythmic expression of the marker of neural activation, cFos, was observed in NAc, medial …

Characterization Of The Circadian Properties Of Runt-Related Transcription Factor 2 (Runx2) And Its Role In The Suprachiasmatic Nucleus, Meghan E. Reale

Electronic Thesis and Dissertation Repository

Circadian rhythms orchestrate physiological, behavioral and cognitive processes in order to anticipate and adapt organisms to key environmental cues. These endogenously driven oscillations are generated by a network of interlocked auto-regulatory transcriptional-translational feedback loops driven forward by the Bmal1/Clock heterodimer transcription factor. Given the ubiquitous and dynamic quality of circadian rhythms, the identification of factors involved in the coordination and regulation of the endogenous oscillations is central in broadening our understanding of biological timing systems. In an examination of gene expression in the mammalian central circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), revealed a previously unreported rhythmic expression of runt-related …

Sexual Reward And Depression, Andrea R. Di Sebastiano

Electronic Thesis and Dissertation Repository

Sexual behavior in male rats is a complex rewarding behavior and many neurotransmitters and neuropeptides play an important role in mediation of sexual performance, motivation and reward. The hypothalamic neuropeptide orexin has been shown play a key role in reward associated with food and drugs of abuse, but the role of this neuropeptide in control of sexual performance, motivation and reward is currently unclear. First, it was shown that orexin neurons in the hypothalamus are activated during sexual performance and reward. Next, using cell specific lesions of orexin neurons it was demonstrated that orexin is involved in arousal and anxiety, …

Fmri Reveals The Neural Correlates Of Real And Pantomimed Tool Use In Humans, Joseph Umberto Paciocco

Electronic Thesis and Dissertation Repository

Although functional magnetic resonance imaging (fMRI) can be used to study the neural mechanisms underlying greatly expanded cognitive functions in humans like tool use, surprisingly little fMRI research has been done on actual tool use. In fact, due to technical constraints, most fMRI studies have used pantomimed actions as a proxy for real use. However, human neuropsychology patients who are impaired at pantomiming often improve when handling a tool suggesting potential neural differences. We used fMRI to record brain activation while 13 right-handed participants performed one of two tasks, real or pantomime tool use with one of two tools, a …

Identification Of A Molecular Opiate-Addiction Memory Switch In The Basolateral Amygdala, Danika C.A. Lyons

Electronic Thesis and Dissertation Repository

The molecular mechanisms involved in acquiring opiate-related associative memories are largely unknown. One neural region implicated in the formation of opiate-related memories is the basolateral nucleus of the amygdala (BLA). Transmission through dopamine (DA) receptors within the BLA controls the formation of opiate-related reward memories (Lintas et al., 2011; Lintas et al., 2012). Specifically, transmission through DA D1 receptors controls opiate reward memory formation in animals that are previously naïve to opiate exposure. However, once opiate dependence and withdrawal are present, intra-BLA DA-mediated control of opiate reward memory processing switches to a DA D2 receptor substrate. These findings demonstrate a …

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

Electronic Thesis and Dissertation Repository

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 …

Effects Of Methamphetamine On Sexual Behavior, Karla S. Frohmader

Electronic Thesis and Dissertation Repository

Methamphetamine (Meth) is a highly addictive psychostimulant associated with enhanced sexual desire, arousal, and sexual pleasure. Moreover, Meth abuse is frequently linked with the practice of sexual risk behavior and increased prevalence of Human Immunodeficiency Virus (HIV). Currently, the neurobiological basis for this drug-sex nexus is unknown. Moreover, there is a lack of studies investigating the effects of Meth on sexual behavior and more importantly, compulsive sex-seeking behavior, under controlled experimental settings in animal models. First, using immuhistochemistry for mating- and Meth-induced neural activation it was demonstrated that Meth administration in male rats activates neurons in brain regions of the …