Life Sciences Commons^™

The Role Of Serotonin In The Estradiol-Dependent Selectivity Of Auditory Regions In Songbirds, Calista J. Henry

Electronic Thesis and Dissertation Repository

Breeding-typical levels of estradiol in songbirds has been shown to lead to selective auditory processing and induce a release of serotonin in auditory regions of the forebrain. These findings triggered the question of whether auditory discrimination is driven by estradiol directly, or by the associated release of serotonin. I treated non-breeding female white-throated sparrows (Zonotrichia albicollis) with either blank implants, 17β-estradiol, serotonin enhancer and blank implants, or serotonin antagonist and 17β-estradiol implants. Birds then heard male conspecific songs or control tones, and ZENK-immunoreactivity was quantified in the caudomedial nidopallium (NCM) and caudomedial mesopallium (CMM). While I did not …

Sex Differences In Mood And Anxiety-Related Outcomes In Response To Adolescent Nicotine Exposure, Tsun Hay Jason Ng

Electronic Thesis and Dissertation Repository

Nicotine dependence is causally linked to increased risk of mood/anxiety disorders in later life. Females are reported to experience a higher prevalence of anxiety/depressive disorders and challenges in smoking cessation therapies, suggesting a potential sex-specific response to nicotine exposure and mood/anxiety disorder risk. However, pre-clinical evidence of sex-specific responses to adolescent nicotine exposure is unclear. Thus, to determine any sex differences in anxiety/depressive-related outcomes, adolescent male and female Sprague Dawley rats received nicotine (0.4 mg/kg; 3x daily) or saline injections for 10 consecutive days, followed by behavioural testing, in-vivo electrophysiology and Western Blot analyses. Our results revealed that adolescent nicotine …

Disentangling The Role Of Parvalbumin-Expressing Interneurons In Stimulus-Response Learning And Cognitive Flexibility, Harleen Rai

Electronic Thesis and Dissertation Repository

Habits enable animals to efficiently navigate their surroundings while tending to more cognitively demanding environmental factors. One mechanism underlying habit is known as stimulus-response (S-R) learning, which takes place in the dorsolateral striatum (DLS). However, there is limited knowledge regarding the complex striatal microcircuits involved in S-R learning and cognitive flexibility. Recently, attention has turned toward the GABAergic Parvalbumin-expressing (PV) interneurons that can modulate striatal outputs. Here, we utilized chemogenetic techniques and touchscreen cognitive assessments to analyze the influence of PV neurons on S-R learning in mice. When PV neurons were inhibited, during the acquisition of a S-R and cognitive …

Recovery From Social Isolation In Drosophila: The Role Of Dopamine And The Autism-Related Gene Nlg3., Ryley T. Yost

Electronic Thesis and Dissertation Repository

Within a group, individuals establish their preferred distance from each other, or social space, a form of social behaviour. The resulting distance depends on the exchange of social cues from others that needs to be perceived and integrated within the organism’s neural circuitry. In humans, social spacing can be impaired in neuropsychiatric disorders such as autism and schizophrenia. When organisms are subject to social isolation, profound changes in social behaviour are observed in a variety of species from insects to mammals, including social space. However, the genetic and molecular mechanisms modulating a behavioural response to isolation and possible recovery remain …

Elucidating The Neural Circuitry Underlying Social Spacing In Drosophila Melanogaster Through The Lens Of Neuroligin 3, Abigail T. Bechard

Electronic Thesis and Dissertation Repository

Social interactions among animals can be complex, and abnormal social behaviours may result in negative fitness consequences for both the individual displaying them, and the entire group. To understand the neural basis of complex social behaviour, we can study simpler behaviours that precede and mediate them. Social spacing, the typical distance between individuals in a group, is an easily quantifiable behaviour in Drosophila melanogaster. Here, I investigated the neural circuitry underlying social spacing through the lens of Autism-candidate gene neuroligin 3. Based on the Nlg3 enrichment pattern in adult fly brains, I hypothesized that nlg3-expressing neurons, along …

The Express Sensorimotor Response Selects Visual Features Based On Instruction, David Youhanna Mekhaiel

Electronic Thesis and Dissertation Repository

In time-sensitive situations, orienting reflexes allow us to move rapidly in response to stimuli. The express sensorimotor response (ESR) is an orienting reflex presenting as a brief burst of muscle recruitment. Previous studies have identified commonalities between ESRs and express saccades, another orienting reflex.

In this study, we investigate if ESRs share in a characteristic of express saccades: preference for faces. In separate blocks, participants were instructed to reach toward one of two simultaneously appearing targets: a face and another image. Muscle activity in the pectoralis major muscle of the reaching arm was recorded using skin surface EMGs.

We …

Investigation Of Neurotransmitter’S Knockdown Effect On Drosophila Melanogaster Female Aggression, Asil N. El Galad

Undergraduate Student Research Internships Conference

Drosophila melanogaster (D. melanogaster) is a popular model organism in neurobiology. While aggression has been studied heavily in male drosophila, there's minimal research on aggression in female drosophila. Neurotransmitters influencing aggressive behaviour in female D. melanogaster are poorly understood. Various neurotransmitters such as dopamine, octopamine, and serotonin influence aggression in D. melanogaster Further investigation of the role of neurotransmitters on aggression is thus important. The purpose of our experiment is to observe the effect of the knockdown of dopamine, octopamine and glutamate on aggression in female D. melanogaster.

The Effects Of Prenatal Cannabis Exposure On The Basolateral Amygdala, Karen Kw Wong

Undergraduate Student Research Internships Conference

Clinical and preclinical studies indicate prenatal cannabis exposure (PCE) pathologically affects fetal brain development and may increase vulnerability to neuropsychiatric disorders, including schizophrenia and mood/anxiety disorders. In review research from our lab suggests that fetal exposure to Δ9-THC sex-selectively impairs mesocorticolimbic (MCL) circuit function. However, there is a distinct lack of focus on PCE models on the BLA. The BLA plays a central role within the MCL where it directly interacts with the VTA, PFC and HIPP. Importantly, our model exhibits significant VTA hyperdopaminergic activity, and sex-specific alterations to PFC/HIPP glutamate firing, alongside region- and sex-specific changes in dopamine (DA), …

The Effect Of Propionic Acid On The Habituation To Social And Non-Social Odour Cues In Adult Male Rats, Cashmeira-Dove P. Tyson

Electronic Thesis and Dissertation Repository

The enteric bacterial metabolite, propionic acid (PPA), elicits physiological and behavioural changes in rodents reminiscent of autism spectrum disorder (ASD). This includes abnormal sensory processing and social behaviour. ASD may contribute to social deficits through impaired habituation; therefore, the present study examined the effects of intraperitoneal PPA on the habituation to social and non-social odours. Adult male rats were injected daily with PPA or the vehicle control, and for 3 days, habituated to a conspecific odour or vanilla extract for 10 minutes. On day 4, rats were exposed to a novel conspecific odour or almond extract for 10 minutes to …

Assessing The Impact Of Lipopolysaccharide On Learning And Memory In Rats, Anahat Luthra

Undergraduate Student Research Internships Conference

The immune system and the central nervous system (CNS) have a bi-direction relationship, modulating one another.⁴ Proinflammatory cytokines released from CNS immune cells have an impact on cognitive processes such as learning and memory.¹ Liposaccharide (LPS), a cell wall component of Gram-negative bacteria, which is used to activate proinflammatory cytokine release has been found to impact learning and memory processes, such as in the anticipatory nausea paradigm (ANP).² Anticipatory nausea and vomiting is that which may occur before a chemotherapy treatment session begins in a patient who has had chemotherapy before. It is caused by triggers like …

Stimulus Duration Alters Temporal Sensitivity In Rat Model Of Audiovisual Perception, Juwairiya F. Ahmad

Undergraduate Student Research Internships Conference

The aim of this experiment was to investigate the effect of stimulus duration on the perceived temporal order judgement in Long Evans rats.

Neuroanatomical Characterization Of Fruitless P2 Neurons And Assessment Of Their Role In Female Mate Receptivity, William Yeung

Electronic Thesis and Dissertation Repository

In behaviourally isolated species, preferential mate choice for conspecifics over heterospecifics is a primary isolating barrier for reducing interspecific gene flow. Drosophila males court heterospecific females more frequently than females are sexually receptive to courting heterospecific males, emphasizing the importance of female mate preference in reproductive isolation. The neurogenetic bases of female mate preference have been elusive historically, but recent research identified the D. melanogaster fruitless (fru) P2 exon to influence both conspecific and heterospecific female receptivity. I have expanded on these findings by creating a transgenic line that expresses Gal4 under fru^P2 regulation. Driving a fluorescent …

The Functional And Structural Consequences Of Aberrant Microglial Activity In Major Depressive Disorder, Jasmine D. Cakmak

Electronic Thesis and Dissertation Repository

Major depressive disorder (MDD) is a highly debilitating neuropsychiatric illness which has been linked with increases in both peripheral and central inflammation, as well as with changes in connectivity. Although countless studies have investigated these two topics, the relationship between neuroinflammation and functional/structural connectivity has not been explored. Using [¹⁸F]FEPPA PET imaging, we measured translocator protein-related (TSPO) microglial activity in the subgenual anterior cingulate cortex (sgACC) and insula and confirmed significantly increased [¹⁸F]FEPPA uptake in depressed patients (N=12) compared to healthy controls (N=23). Using a seed-based ROI analysis of fMRI data, we found that patients show …

Investigating The Effects Of Maternal Immune Activation On Sensory Processing: Timing, Immune Mechanisms, And Gene-Environment Interactions, Faraj Haddad

Electronic Thesis and Dissertation Repository

Maternal infection during the first or second trimester of pregnancy poses a risk factor for the child to have neurodevelopmental disorders like autism spectrum disorder (ASD) and schizophrenia. Various clinical and preclinical studies have shown that the maternal immune response to infection, also known as maternal immune activation (MIA), can disrupt fetal brain development.

Over the past two decades, MIA has been studied in rodents using the Polyinosinic Polycytidylic acid (Poly I:C) rodent model. Poly I:C has a molecular pattern resembling viruses that can induce a robust immune response. Following exposure to Poly I:C MIA, rodent offspring exhibit many brain …

Investigation Of The Hsp90 Co-Chaperone, Sti1, In Cellular Resilience And Neurodegenerative Diseases, Rachel E. Lackie

Electronic Thesis and Dissertation Repository

In neurodegenerative diseases, certain proteins misfold and form toxic aggregates that cause brain matter atrophy, leading to decline in motor and/or cognitive functions. To maintain cellular proteostasis and survival, molecular chaperones regulate protein maturation and help to prevent aberrant protein aggregation. The molecular chaperone Hsp90 regulates hundreds of proteins and interestingly, several of those are misfolded in neurodegenerative diseases. Stress inducible-phosphoprotein-1 (STI1, STIP1), an Hsp90 co-chaperone, orchestrates client protein transfer between chaperones Hsp70 and Hsp90 through physical interactions with both chaperones. Notably, previous work in yeast, worms, and mouse neurons all showed that STI1 protects organisms against stressors and amyloid-like …

Cholinergic Modulation Of Behaviour, Ornela Kljakic

Electronic Thesis and Dissertation Repository

The cholinergic system is one of the most influential and essential signalling systems in the body. In the brain, cholinergic neurons innervate many brain regions where they influence a wide variety of behaviours. However, the precise role of each cholinergic region on distinct types of behaviour is not well known. Furthermore, in recent years there has been evidence that many cholinergic neurons in the brain have a capacity for co-transmission. Yet the functional significance of secreting two classical neurotransmitters from the same neuron is still largely unidentified. In this thesis, we investigated how different cholinergic nuclei modulate behavioural functions. To …

Investigating Cognitive Impairment In Tdp-43 Mouse Models Of Ftd-Als Using Automated Touchscreens, Keon Coleman

Electronic Thesis and Dissertation Repository

TAR-DNA-binding protein 43 (TDP-43) misfolding and aggregation is a major pathological hallmark of frontotemporal dementia-amyotrophic lateral sclerosis (FTD/ALS). FTD/ALS is characterized by motor and cognitive impairment, with cognitive impairment frequently reported before the onset of classical motor symptoms. Yet, treatment for cognitive decline in FTD/ALS is lacking, and robust cognitive phenotypes related to TDP-43 proteinopathy have not been established for most mouse models of FTD/ALS. Herein, we used automated touchscreen technology to assess executive function (affected in FTD/ALS) in male TDP-43^Q331Klow and ^-G348C FTD/ALS transgenic mice. The touchscreen pairwise visual discrimination task revealed impairments in 4-5-month-old TDP-43^Q331Klow and …

Assessment Of Autistic-Like Behaviour Of Mice Lacking Atrx In Forebrain Glutamatergic Neurons, Nicole A. Martin-Kenny

Electronic Thesis and Dissertation Repository

Mutations in ATRX, which encodes a chromatin remodeling protein, have been identified in patients with autism and are associated with ATR-X syndrome, a genetic disorder characterized by cognitive deficits, developmental delays, and autistic-like behaviour. Despite the relationship between ATRX and autism, it is not yet known how mutations lead to autistic behaviour. To investigate this relationship, we generated two mouse models displaying distinct timing of Atrx inactivation in forebrain excitatory neurons. With these models, we performed behavioural paradigms to assess behaviour related to autism. Behavioural testing revealed that the conditional deletion of Atrx in differentiated forebrain neurons during …

The Role Of Histone Demethylases In Learning And Memory In The Mushroom Body Of Drosophila Melanogaster, Crystal Keung

Electronic Thesis and Dissertation Repository

Intellectual disability (ID) is a neurodevelopmental disorder associated with many epigenetic regulators and chromatin modifying enzymes like histone lysine methyltransferases (KMTs) and demethylases (KDMs). Here, I systematically investigate the role of 7 KDMs: Su(var)3-3, KDM2, Lid, CG2982, UTX, KDM4B, JHDM2, and 1 KMT: trr in the context of learning and memory using Drosophila melanogaster. Genetic knockdown of each gene in the mushroom body (MB) of flies are tested for short- and long-term memory impairment using courtship conditioning. Knockdown of 6 KDMs and trr resulted in memory loss. MB morphology was analyzed to determine potential cause of memory loss. …

The Role Of Adult Hippocampal Neurogenesis In Depression-Relevant Reward-Related Behaviours, Katrina Zmavc

Electronic Thesis and Dissertation Repository

The variability in the symptomatology of depressive disorders and antidepressant treatment response has led to an increased interest in the molecular, cellular, and circuit mechanisms of many aspects of affect. Evidence suggests a reduction in adult hippocampal neurogenesis (AHN) is associated with an increase in depression-like behaviour, though much of this evidence has been from studies using aversive tests (e.g., forced swim test). Here, I used touchscreen operant chambers, which allow for non-aversive and translational testing, to test the hypothesis that AHN plays a contributing role in emotion regulation. A panel of three touchscreen tests were chosen to assess different …

Assessing The Role Of Drosophila Melanogaster Neuroligin 3 On Social Spacing And Climbing Behaviour, J. Wesley Robinson

Electronic Thesis and Dissertation Repository

Autism spectrum disorders can be clinically defined in part by impairments of social interactions. Social interactions can be modeled in Drosophila melanogaster with behaviours such as social spacing. Here, I examined the effects of autism-related gene neuroligin 3 on fly social spacing. I hypothesized if neuroligin 3 is mutated or gene expression is targeted for knockdown, then flies will have altered social space in males and females at different ages. Using the social space assay, I found that different mutations to neuroligin 3 change the fly’s behavior, in a mutation and sex-specific manner. Using an antibody against Nlg3, I localized …

Optimization Of The Touchscreen-Based Visuomotor Conditional Learning Task In Mice, Oren Princz-Lebel, David I. Wasserman, Miguel Skirzewski, Penny A. Macdonald, Lisa M. Saksida, Tim J. Bussey

Western Research Forum

The translational gap between animal models and clinical trials is a longstanding, yet largely unresolved, limitation in the study of cognition. This discrepancy is largely due to the differences in how cognition is assessed in animal models compared to those in clinical populations. In the stimulus-response (S-R) learning literature, for example, the techniques used to assess the acquisition of habitual behaviour differ greatly across species, leading to poor cross-species translation and often conflicting results. As a result, we set out to optimize a S-R learning task in mice using the touchscreen-based operant technologies. Similar to human studies, this touchscreen technique …

Cognition And The Brain Of Brood Parasitic Cowbirds., David F Sherry, Mélanie F Guigueno

Psychology Publications

Cowbirds are brood parasites. Females lay their eggs in the nests of other species, which then incubate the cowbird eggs and raise the young cowbirds. Finding and returning to heterospecific nests presents cowbirds with several cognitive challenges. In some species, such as brown-headed cowbirds (Molothrus ater), females but not males search for and remember the locations of potential host nests. We describe recent research on sex differences in cognition and the hippocampus associated with this sex difference in search for host nests. Female brown-headed cowbirds perform better than males on some, but not all, tests of spatial memory and females …

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit

Electronic Thesis and Dissertation Repository

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …

Characterizing The Sensorimotor Properties Of A Rapid Visuomotor Reach Movement On Human Upper Limb Muscles, Chao Gu

Electronic Thesis and Dissertation Repository

Humans and other primates rely heavily on vision as a primary sensory input to drive our upcoming volitional motor actions. Our motor system makes so many of these visual-to-motor transformations that they become ubiquitous in our daily lives. However, a central question in systems neuroscience is how does the brain perform these transformations?

Reaching movements have been an ideal model for studying volitional motor control in primates. Broadly, these visually-guided reach movements contain three inherent sensorimotor components: an action selection component, a motor execution component, and a motor learning component. A core assumption is that as reach movements become more …

Cannabinoid Transmission In The Basolateral Amygdala Modulates Prefrontal Cortex And Ventral Hippocampal Activity, Brian J. Pereira

Electronic Thesis and Dissertation Repository

The cannabinoid system is important for maintaining neuron-to-neuron communication within the mammalian brain. One of the most commonly used substances to alter the cannabinoid system is cannabis. Individuals who are exposed to cannabis report having dissociable effects; both positive and negative. High amounts of THC have been commonly associated with the negative effects of cannabis, whereas CBD can be used to counter these. Pre-clinical evidence suggests that the combination of the two compounds can produce a therapeutic benefit for individuals who are susceptible to the effects of THC. The present study investigates whether the combination of THC+CBD can prevent electrophysiological …

Characterizing The Cognitive And Emotional Effects Of Delta-9-Tetrahydrocannabinol In Distinct Hippocampal Sub-Regions, Dinat Khan

Electronic Thesis and Dissertation Repository

The objective of this study is to determine the potential differential effects of THC in the DH or VH sub-regions, as well as the upstream effects on PFC neuronal activity and oscillations. Rodents used for electrophysiology were infused with THC or vehicle in the DH or VH regions, combined with PFC recordings. Additionally, a battery of behavioural paradigms was performed. Deficits in short-term memory when THC was infused into both regions was observed, however working memory was impaired with VH infusions only. This could be due to THC-induced dysregulation in the PFC, as beta oscillations were significantly decreased selectively in …

Behavioural And Anatomical Effects Of Unilateral Injection Of Botulinum Neurotoxin A In The Entopeduncular Nucleus Of A Parkinsonian Rat Model, Adrianna Tsang

Electronic Thesis and Dissertation Repository

Loss of dopamine in Parkinson’s disease is associated with glutamatergic hyperactivity of the subthalamic nucleus. Pharmacological and electrical therapies aimed to suppress this overactivity favourably alleviate parkinsonian motor symptoms. No study has explored the potential of botulinum neurotoxin A in the central nervous system beyond cholinergic blockage despite evidence of its ability to inhibit glutamate release. Thus, the present study investigates the effect of selective suppression of hyperactive glutamatergic input from the subthalamic nucleus to the entopeduncular nucleus by botulinum neurotoxin A in a parkinsonian model. Unilateral 6-hydroxydopamine lesioned rodents received microinfusions of botulinum neurotoxin A or vehicle into the …

Psychotropic Effects Of Cannabis Components On The Mesolimbic Dopaminergic System, Christopher Norris

Electronic Thesis and Dissertation Repository

The two most abundant phytochemical compounds in cannabis are cannabidiol (CBD) and ∆⁹-tetrahydrocannabinol (THC). THC is the primary psychoactive component of cannabis and is a partial CB₁ receptor (CB₁R) agonist. THC is believed to be responsible for the motivational and dependence-producing effects of cannabis and causes psychotomimetic and affective processing disturbances. Conversely, CBD, is non-psychoactive, acts as a 5-HT_1A receptor agonist, antagonizes CB₁Rs, and possesses both anti-psychotic and anxiolytic properties. The neural substrate believed to be responsible for many of the effects of cannabis is the dopaminergic, mesolimbic reward pathway which is …

Characterizing Mekk1: Candidate Behavioural Isolation Gene, Caryn Dooner

Electronic Thesis and Dissertation Repository

Behavioural isolation can occur due to divergence in aspects of courtship and mating, and can contribute to reproductive isolation. The purpose of this study is to determine how a gene, Mekk1, contributes to female rejection behaviour between D. melanogaster and D. simulans. Unique polymorphisms were identified within D. simulans Mekk1 that could contribute to behaviour, most of which are non-coding. Both transcripts of Mekk1 appear to be expressed at similar levels in D. simulans and D. melanogaster. These data also indicate that Mekk1 may be expressed in a specific region of the brain called the mushroom body, …