Neuroscience and Neurobiology Commons^™

The Subplate And Its Role In The Gaba System In The Prefrontal Cortex, Gaeul Kyla Lee

Electronic Thesis and Dissertation Repository

During early brain development, the subplate relays thalamocortical afferents. Lesions to the subplate have been implicated in developmental abnormalities of cortical GABAergic circuits. This thesis examined the effects of subplate lesions in the prefrontal cortex of rats on the expression of GABA markers (parvalbumin and GAD67) and GABA synapse maturation [potassium-chloride cotransporter (KCC2) and sodium-potassium- chloride cotransporter (NKCC1)] with relevance to the characterization of a rat model for schizophrenia. Lesions were made on postnatal day 1 (P1). Lesioned and control rats were sacrificed between P5 and P90 and immunolabelled for parvalbumin, GAD67, KCC2, and NKCC1. We found decreased parvalbumin expression …

Role Of Cholinergic Receptors In Prefrontal Activity Of Nonhuman Primates During An Oculomotor Rule-Based Working Memory Task, Alex J. Major

Electronic Thesis and Dissertation Repository

The ability to flexibly react to our dynamic environment is a cardinal component of cognition and our human identity. Millions across the globe are affected by disorders of cognition, affecting their ability to live independently. Prefrontal cortex is required for optimal cognitive functioning, but its circuitry is often disrupted in conditions of impaired cognition. In addition, the cholinergic system is vital to optimal executive function, but this is disrupted in a number of conditions, including Alzheimer’s disease and schizophrenia. The actions of cholinergic receptors were explored in this project with local application of cholinergic compounds onto prefrontal neurons as rhesus …

Mechanisms Underlying Executive Function Deficits, Sagar Jayawantrao Desai

Electronic Thesis and Dissertation Repository

In our daily life, we come across situations where we meet unanticipated challenges, we must take certain decisions, pay attention, be flexible and inhibit impulsive actions to achieve goal directed behaviour. During these processes, we unknowingly use sets of interdependent cognitive processes collectively called ‘executive function’. Executive function is mainly regulated by the frontal lobe. Impaired executive function is associated with disorders such as schizophrenia, Alzheimer’s disease, autism and attention deficit hyperactivity disorder (ADHD).

In this thesis, we investigated neurotransmitters and interactions among them regulating executive function. Further, we investigated mechanisms underlying those interactions mediating executive function in rats using …

Muscarinic Attenuation Of Mnemonic Rule Representation In Macaque Dorsolateral Prefrontal Cortex During A Pro- And Anti-Saccade Task, Alex J. Major

Electronic Thesis and Dissertation Repository

Maintenance of context is necessary for execution of appropriate responses to diverse environmental stimuli. The dorsolateral prefrontal cortex (DLPFC) plays a pivotal role in executive function, including working memory and representation of abstract rules, and is modulated by the ascending cholinergic system through nicotinic and muscarinic receptors. Muscarinic receptors’ effect on local primate DLPFC neural activity in vivo during cognitive tasks remains poorly understood. Here we examined the effects of muscarinic receptor blockade on rule-related activity in the macaque prefrontal cortex by combining iontophoretic application of the general muscarinic receptor antagonist scopolamine with single-unit recordings while monkeys performed a rule-guided …

Investigating The Primate Prefrontal Cortex Correlates Of Cognitive Deficits In The Ketamine Model Of Schizophrenia, Kevin J. Skoblenick

Electronic Thesis and Dissertation Repository

The World Health Organization has classified schizophrenia as one of the five leading causes of disability worldwide. Afflicting almost 1% of the world’s population, the disease’s greatest impact stems from its reduction in patients’ cognitive faculties. In order to better study these impairments, a pharmacological model has been developed using the NMDA antagonist, ketamine. This disease model successfully recreates the cognitive dysfunction of schizophrenia, allowing researchers to search for associated electrophysiological changes.

In this project I examined the behavioural and neurophysiological effects of ketamine on non-human primates performing the anti-saccade task. Success in this task requires a degree of cognitive …

Spatial And State-Dependent Effects Of Transcranial Magnetic Stimulation Of Prefrontal Cortex In Non-Human Primates, Chao Gu

Electronic Thesis and Dissertation Repository

The indirect effects of transcranial magnetic stimulation (TMS) within a distributed neural network are still largely unknown. Here we propose to use the non-human primate (NHP) oculomotor system as an animal model for investigating the effects of TMS. Across three animals, single pulses of TMS to the prefrontal cortex (PFC), including the frontal eye fields (FEF), reliably evoked a contralateral head turning synergy, similar to what is seen following intracortical microstimulation. Furthermore, double pulses of TMS paired with the memory-guided saccade paradigm only evoked neck muscle activity preceding contralateral saccades, showing similar state-dependency as previously observed in human TMS studies. …

Flexibly Adapting To Emotional Cues: Examining The Functional And Structural Correlates Of Emotional Reactivity And Emotion Control In Healthy And Depressed Individuals, Steven G. Greening

Electronic Thesis and Dissertation Repository

The ability of emotionally significant stimuli to bias our behaviour is an evolutionarily adaptive phenomenon. However, sometimes emotions become excessive, inappropriate, and even pathological, like in major depressive disorder (MDD). Emotional flexibility includes both the neural processes involved in reacting to, or representing, emotional significance, and those involved in controlling emotional reactivity. MDD represents a potentially distinct form of emotion (in)flexibility, and therefore offers a unique perspective for understanding both the integration of conflicting emotional cues and the neural regions involved in actively controlling emotional systems.

The present investigation of emotional flexibility began by considering the functional neural correlates of …

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 …