Browsing by Subject "Prefrontal Cortex"

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    NMDA receptors underlie stress-induced dynamic changes in prefrontal cortical networks: plasticity and function.
    (2011-01) Parent, Marc-Alexander L.T.
    The prefrontal cortex (PFC) is a region in the frontal lobe of the cerebral cortex necessary for the proper execution of cognitive behaviors such as attention, memory, and the ordering of actions to accomplish a task. In rodents, lesions of the medial prefrontal cortex (mPFC) impact visiospatial working-memory (vsWM) functions. Neurons in the cerebral cortex are typically silent in alert animals but can become persistently active when brain networks engage them to participate in computations necessary to accomplish a task. During vsWM tasks, neurons in mPFC become persistently active for the delay period of a WM task. The persistent activation of neurons in mPFC by local networks during the delay period of a working memory task in vivo has been suggested to represent a basic neural substrate for maintenance of an internal representation. Stress can alter the performance of animals attempting working memory tasks, and its effects are dynamic over the span of days following a single exposure. Immediately following stress, vsWM is negatively affected and performance on a vsWM task is hindered, while four to twenty-four hours following exposure to stress, vsWM is enhanced. It has been hypothesized that plasticity in local mPFC glutamatergic networks in vivo, driven by stress-response mediators, alters AMPA- and NMDA-mediated neurotransmission as a function of the number of stress exposures and that this plasticity affects persistent, network-driven activity. A previous study has shown that both AMPA- and NMDA-mediated neurotransmission are upregulated twenty-four hours after exposure to mild FS stress (Yuen et al., 2009). The following doctoral thesis supports this conclusion and extends this work to quantify the effects of multiple stress exposures, over several days, on mPFC plasticity and describes a correlation between enhanced glutamatergic synaptic drive and changes in persistent activity. In animals exposed to multiple days of ten-minute, forced-swim stress, NMDA-mediated glutamatergic neurotransmission was upregulated relative to unstressed, naïve animals while AMPA-mediated neurotransmission and intrinsic cellular phenomena remained unaffected. Close examination of isolated NMDA currents from neurons in three-day stressed mice revealed a decrease in the decay rate of these currents relative to naive animals. This augmentation of NMDA-ergic tone yields greater charge entry that could potentially increase the impact of synaptic drive on neuronal activity as well as enhance synaptic integration. The upregulation of NMDA-mediated neurotransmission in three-day stressed animals was found to occur via the upregulation of the NR2B subunits at synaptic NMDA receptors. Together, a decrease in NMDA current decay rate via inclusion of NR2B subunits and the lack of evidence for stress-induced AMPA current modulation resulted in an increase in NMDA-to-AMPA ratio (NAR) at synaptic mPFC networks. These observed changes in glutamatergic neurotransmission, after a single or multiple exposures to forced swim, are paralleled by changes in persistent activity. Individual PA events were recorded from naïve, one-day and three-day stressed mice. PA events recorded from both stressed groups were increased in duration relative to naïve animals. These data support the conclusion that stress regulates glutamatergic neurotransmission in the mPFC, affecting the ability of neurons to remain persistently active.
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    Untangling theory as theoretical framework for understanding the functions of brain systems dedicated to economic decision-making
    (2020-08) Yoo, Seng Bum
    The long tradition of neuroscience has focused on dissecting systems and searching for the unique functional properties of each anatomical area. This tradition creates separate fields of study within systems neuroscience: the field of study of the visual system, that which studies the motor system, that which studies the memory system, etc. The field of value-based decision-making builds upon this tradition and successfully claims new territory in the prefrontal cortex (PFC). In fact, now neuroscience as a field has a very robust understanding of the prefrontal cortex. The dominant understanding in the field posits that the information in PFC is all abstract: like utility of certain objects or preferences (Padoa-Schioppa 2011). This position holds belief that no concrete information related to sensory or motor systems exists in the PFC. In parallel, more and more studies have subdivided the prefrontal cortex by anatomy and cytoarchitecture, assigning a unique functionality to each region (Wise 2012). However, is it really true that the value-based decision-making system is unique compared to the other systems of the brain? Is it true the PFC consists of hundreds or thousands of patches, each with its own unique functionality? If not, what can be the alternative? With the dissertation, we would like to discuss counterevidence against this widely believed framework of functional specialization. We will argue that the prefrontal cortex encodes non-abstracted variables like spatial information, and there are many similarities between the different brain regions in the prefrontal cortex that have largely been ignored. There can be many reasons why the field of neuroscience, specifically the study of value-based decision-making, has been biased towards a functional specialization framework. We hypothesize that this understanding is the result of more controlled, simplistic tasks with the aim of generating reductionist explanations. Using a high-dimensional and natural task paradigm where many sensorimotor variables change and affordances vary accordingly generates evidence counter to this view. We developed a task that mimics the hunting of animals where every agent must process changing information dynamically and interactively. Our result suggests that even a single brain area, the dorsal anterior cingulate cortex (dACC), encodes position and kinematic variables that influence the subject's instantaneous decision. We further sought to characterize the computations underlying the subject's performance. We found that the subject's behavior is well explained by the subject predicting the future position of the rewarding agent by an internal model. Furthermore, we find that dACC neurons represent positional and kinematic variables that would be critical for predicting the future. These results provide evidence against the claim that brain areas usually associated with value-based decision-making brain are dedicated solely to processing unique information related to abstract value. Instead, finding kinematic information about self and other agents suggests that information is distributed across brain areas. In addition, this outcome could provide insight about the benefits of continuous and naturalistic tasks. In the final section of this manuscript, we will define the necessary components of continuous decision-making and discuss the benefits of these task paradigms.
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    Which way do I go? Strategic representations in rat prefrontal cortex on spatial decision tasks
    (2014-10) Powell, Nathaniel
    The role of the Prefrontal Cortex (PFC) in animal behavior is both complex and subtle. This dissertation concerns the role of rat PFC on spatial decision- making tasks, particularly how it represents strategies or rules necessary to solve these tasks. First I review the current state of knowledge about the role of the rat PFC in regard to behavior and decision-making (Chapter 1). Then I describe the spatial decision-making tasks and electrophysiological recording techniques I used to explore the role of PFC in rats (Chapter 2). Using one of these tasks, I found overlapping populations of PFC neurons that simultaneously encoded mul- tiple relevant task parameters, including some cases in which mulitple parameters were encoded by single neurons (Chapter 3). I also describe the spatial firing properties of PFC neurons on these tasks and conclude that although these cells do not seem to directly represent space per se, there are important differences in both single-cell and population representations that corresponded to the ani- mal's location on spatial tasks (Chapter 4). Finally, using a population decoding approach that takes advantage of the spatially coded information in the cells, I identify transitions between different strategic representations in the PFC of an- imals performing these tasks. In general the transition between states occurred after animals received information that caused them to change their strategy but before the actual change in their behavior. Additionally, these transitions cannot be accounted for solely on the basis of changes to either sensory information or mo- tor output, which proves that these transitions between strategic representational states are cognitive processes (Chapter 5).