Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1995. / Includes bibliographical references (leaves 46-47). / by James Davis Thomas. / M.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2008. / Page 131 blank. / Includes bibliographical references. / As our understanding of the brain grows, neuroscientists find themselves increasingly in the role of cartographer. Thus far, cortical maps have been found primarily in early input and late output areas, however they may also occur in higher-level regions of the brain that perform more complex functions. An example of such a region is the objectselective ventral visual cortex (VVC) in humans. This region, which is involved in the high-level task of object recognition, is comprised of several functionally defined, category-selective subregions that are laid out with remarkable systematicity and consistency across individuals. In this thesis, I use fMRI to test several hypotheses about the nature of object representations and the dimensions along which object-selective cortex might be organized. In the first study, I find evidence supporting the existence of domain-specific regions. Results from the second set of studies suggest that temporal associations do not guide the overall organization of VVC, and also provide contradictory evidence against a long-standing hypothesis that the VVC is organized based on conceptual knowledge about objects and, specifically, the distinction between animate and inanimate objects. Instead, my results suggest that associations between objects and motor actions may play a role in the location of category selectivities for a subset of object classes. Results from a third set of studies demonstrate that computational demands for acuity or spatial integration cannot account for location biases in category-selective regions, and instead suggest that experience with objects at specific retinal locations may serve as an organizing dimension. Moreover, these studies reveal systematic differences in the amount of location information contained in category-selective regions on the ventral temporal versus lateral occipital surfaces. / (cont) In sum, the studies described in this thesis address several hypotheses about the large-scale organization of VVC, and, in doing so, advance our understanding of the principles that govern the layout of maps in higher-level, object-selective cortex. / by Rebecca Frye Schwarzlose. / Ph.D.

Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2014. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Cataloged from student-submitted PDF version of thesis. / Includes bibliographical references (pages 239-249). / The most fascinating function of the nervous system is its ability to generate consciousness, the subjective experience or qualia that distinguishes awake life from dreamless sleep. How consciousness is generated is an ancient philosophical question which has proven resistant to scientific analysis. While the human brain is known to generate consciousness, its complexity prevents acquisition of a mechanistic understanding of consciousness. Therefore, I chose to study the much simpler nervous system of the nematode Caenorhabditis elegans. I tested worms for a specific kind of learning, called trace conditioning, which correlates with conscious awareness in humans, under the assumption that if worms were able to trace condition, they might also be capable of conscious awareness. However, I was not able to show trace conditioning in worms, so the question of whether worms exhibit consciousness remains unresolved. In the process of using light in learning experiments, I noticed that worms stop feeding immediately after being exposed to short wavelength (UV) light. Curious about whether worms might actually have a subjective experience in response to light akin to primitive vision, I investigated the molecular and neural mechanisms that control this behavioral response. I identified the I2 pharyngeal neuron as a cellular light sensor required for the speed of feeding inhibition. Hydrogen peroxide elicited behavioral and cellular responses strikingly similar to those caused by light. The sensing of both light and hydrogen peroxide were mediated by the LITE-1 and GUR-3 proteins, both putative gustatory receptors, as well as by the conserved antioxidant enzyme peroxiredoxin PRDX-2. My results suggest that the LITE-1/GUR-3 family of receptors likely detects light through its generation of hydrogen peroxide or of another redox product. This is a novel mechanism by which light can be sensed. Additionally, by studying the worm's feeding response to light, I identified a pattern of neural function in which neurons appear to act independently to control sequential phases of a behavior. In the first phase, light rapidly inhibited feeding, with the I2 neuron sensing light and releasing glutamate likely onto pharyngeal muscle, where it was received by the AVR-15 glutamate-gated chloride channel. In the second phase, the inhibition of feeding was maintained via a circuit that included the extrapharyngeal neuron RIP and pharyngeal neurons I1 and MC. Finally, in the third phase, light stimulated pharyngeal contractions via the M1 neuron. These three circuits appear to be independent. I conclude that what initially appeared to be a simple reflex is instead a sequence of behavioral responses coordinated by independent neural circuits, suggesting a motif I term "parallel temporal tiling." Although I am still uncertain about whether worms have a subjective experience of light, this research will serve as a foundation for future work aimed at this very question. / by Nikhil Bhatla. / Ph. D. in Neuroscience

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1993. / Includes bibliographical references (p. 197-209). / by Neal Jay Pearlmutter. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2014. / Cataloged from PDF version of thesis. Vita. / Includes bibliographical references (pages 123-143). / Working memory is the ability to hold information "online" over a delay in order to perform a task. This kind of memory is thought to be encoded in the brain by persistent neural activity that outlasts the presentation of a stimulus. Interestingly, patients with schizophrenia, a heritable neurological disorder, perform poorly in working memory tasks that require the retention of a target in space, indicating that persistent neural activity related to spatial locations may be impaired in the disease. At the biophysical level, NMDA receptors and dopamine receptors have been continually implicated in supporting persistent activity during spatial working memory. Perhaps relatedly, drugs that target the dopamine system are regularly used in the treatment of schizophrenia, and drugs that target NMDARs induce schizophrenia-like symptoms in healthy individuals. In this thesis, I seek to further examine the possible connection between NMDA receptors, the dopamine system, and schizophrenia-related working memory deficits. We find that homocysteine, a dopamine breakdown product that is upregulated in the blood of schizophrenia patients, strongly impacts NMDAR currents by reducing channel desensitization and altering peak amplitude. Additionally, we find that the dopamine system itself, which is traditionally studied in areas like striatum and prefrontal cortex, is organized in a behaviorally relevant pattern in the superior colliculus (SC), a brain region that shows persistent activity during spatial working memory tasks. The electrophysiological affects of dopamine on the SC suggest that dopamine dysregulation could have previously unexplored effects on spatial attention, sensorimotor integration, and working memory. / by Andrew D. Bolton. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1992. / Includes bibliographical references (leaves 172-177). / by Jacob Feldman. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 81-93). / The frontal-striatal reward network is involved in many reward-related behaviors, including decision-making and those related to psychiatric disease. One important class of decisions involves the conflict between immediate rewards and delayed gratification. Temporal discounting preferences reflect how a person makes decisions that involve tradeoffs over time. A fundamental question is how people vary and what accounts for this variation in temporal discounting preferences, both behaviorally and neurobiologically. In addition, psychiatric diseases, such as social anxiety, are associated with deficits in behaviors that involve social reward. Here I report two experiments that provide evidence for two major factors that contribute differences in temporal discounting preferences: personality traits and the underlying frontal-striatal reward network, both during task and at rest. Finally, I report underlying differences in the organization of the frontal-striatal reward network in social anxiety disorder. In the first study, I investigated the frontal-striatal reward network that underlies personality traits and the association of personality with temporal discounting preferences. Higher neuroticism was associated with a greater preference for immediate rewards and greater impulsivity, and higher conscientiousness with a greater preference for delayed rewards and less impulsivity. Executive-control and reward regions in the frontal-striatal reward network were more activated when higher conscientiousness participants selected a smaller-sooner reward and, conversely, when higher neuroticism participants selected a larger-later reward. Both cases involved choices that went against predispositions implied by personality. In the second study, I investigated how restingstate intrinsic functional brain organization (functional connectivity) of the frontal-striatal reward network varies with temporal discounting preferences. Increased patience and decreased impulsivity were associated with stronger functional connectivity between the nucleus accumbens and prefrontal executive control regions, including the dorsolateral prefrontal cortex. These findings reveal that the intrinsic strength of the frontal-striatal network is associated with differences in temporal discounting preferences. In the third network in social anxiety disorder. There was decreased functional connectivity between the nucleus accumbens and other reward regions, including the ventromedial prefrontal cortex, and decreased functional connectivity between the ventromedial prefrontal cortex and executive control regions of the prefrontal cortex. Taken together, these results indicate that the frontal-striatal reward network is associated with individual differences in reward-related behavior. / by Joshua Manning. / Ph. D.

Thesis (Ph. D. in Neuroscience)--Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2013. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Neuronal communication requires a spatially organized synaptic apparatus to coordinate neurotransmitter release from synaptic vesicles and activation of postsynaptic receptors. Structural remodeling of synaptic connections can strengthen neuronal communication and synaptic efficacy during development and behavioral plasticity. Here, I describe experimental approaches that have revealed how the actin cytoskeleton participates in transynaptic signaling to control synapse assembly. I also describe my studies on how regulation of endocytic trafficking controls synaptic growth during neuronal development. To identify regulators of synapse assembly, I carried out a large-scale EMS mutagenesis screen of the second chromosome. From this screen I identified a mutation in actin 57B that disrupts synaptic morphology and presynaptic active zone organization. Actin 57B is one of six actin genes in Drosophila and is expressed in body wall muscle during larval development. The isolated allele harbors a point mutation disrupting a highly conserved amino acid present throughout the actin family. Homozygous mutant larvae show impaired alignment and spacing of presynaptic active zones. Additionally, disruption of the organization of the postsynaptic density is observed, with mislocalization of the Spectrin cytoskeleton and the PSD-homolog Disc-Large. Phallodin staining reveals a severe disruption of postsynaptic actin surrounding presynaptic boutons, with the formation of aberrant large actin swirls. Based on these results, we hypothesize that the loss of a synaptic interaction mediated by actin 57B leads to disruption of postsynaptic cytoskeletal organization and dysregulation of signals required to organize presynaptic active zones. Additionally, I present data that provide new insights into the mechanisms controlling synaptic growth signaling during transit through the endocytic pathway. Nervous Wreck (Nwk) is a presynaptic F-BAR/SH3 protein that regulates synaptic growth signaling in Drosophila. Here, I show that Nwk acts through a physical interaction with Sorting Nexin 16 (SNX16). SNX16 promotes synaptic growth signaling by activated BMP receptors, and live imaging in neurons reveals that SNX16-positive early endosomes undergo transient interactions with Nwkcontaining recycling endosomes. We identify an alternative signal termination pathway in the absence of Snx16 that is controlled by ESCRT-mediated internalization of receptors into the endosomal lumen. Our results define a presynaptic trafficking pathway mediated by SNX116, NWK and the ESCRT complex that functions to control synaptic growth signaling at the interface between endosomal compartments. Together, these experiments have expanded our understanding of the molecular mechanisms that control synaptic growth and assembly, highlighting the role of the postsynaptic actin cytoskeleton and the presynaptic endosomal trafficking pathway as key regulators. / by Aline D. Blunk. / Ph.D.in Neuroscience

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2001. / Includes bibliographical references (leaves 129-142). / The Words-and-Rules theory (WR) posits that different mental processes underlie regular and irregular past tense formation: regular forms are rule-generated ('add -ed'), whereas irregular forms are retrieved from memory. These mental processes are hypothesized to engage distinct neural mechanisms. The goal of the present thesis was to localize and differentiate the neural substrates of regular and irregular past tense generation. Two neuroimaging techniques, magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) were used to test healthy, right-handed subjects who were native speakers of English in a past tense production paradigm, in addition to a lexical access study. The results indicate that there is a dissociation in both the time course of activation and brain areas involved for the regular vs. the irregular past tense formation. / by Jaemin Rhee. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2006. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Includes bibliographical references (p. 87-100). / Despite decades of evidence for functional plasticity in the adult brain, the role of structural plasticity in its manifestation remains unclear. cpg15 is an activity-regulated gene encoding a membrane-bound ligand that coordinately regulates growth of apposing dendritic and axonal arbors and the maturation of their synapses. Here we compare cpg15 expression during normal development of the rat visual system, with that seen in response to dark rearing, monocular retinal action potential blockade, or monocular deprivation. Our results show that: (1) cpg15 expression in visual cortex correlates with the electrophysiologically mapped critical period for development of eye-specific preference in the primary visual cortex. (2) Dark rearing elevates adult levels of expression. (3) A component of cpg15 expression is activity-dependent after the peak of the critical period. (4) At the peak of the critical period, monocular deprivation decreases cpg15 expression more than monocular TTX blockade. And (5) cpg15 expression is robust and regulated by light in the superficial layers of the adult visual cortex. / (cont.) This suggests that cpg15 is an excellent molecular marker for the visual system's capacity for plasticity and predicts that neural remodeling normally occurs in the extragranular layers of the adult visual cortex. To examine the extent of neuronal remodeling that occurs in the brain on a daily basis, we used a multi-photon based microscopy system for chronic in vivo imaging and reconstruction of entire neurons in the superficial layers of the rodent cerebral cortex. Here, we show the first unambiguous evidence of dendrite growth and remodeling in adult neurons. Over a period of months, neurons could be seen extending and retracting existing branches, and in rare cases adding new branch tips. Neurons exhibiting dynamic arbor rearrangements were GABA positive non-pyramidal interneurons, while pyramidal cells remained stable. These results are consistent with the idea that dendritic structural remodeling is a substrate for adult plasticity and suggest that circuit rearrangement in the adult cortex is restricted by cell type-specific rules. / by Wei-Chung Allen Lee. / Ph.D.