Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1994. / Includes bibliographical references. / by Corinna E. Lathan. / Ph.D.

Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Social cognitive abilities undergo drastic changes throughout childhood. Theory of mind (ToM), the ability to reason about the mental states of others, is a core social cognitive ability that is crucial for navigating the social world. A majority of prior fMRI research on ToM has characterized the functional response in brain regions that are preferentially recruited to reason about the minds of others in adults. By contrast, a majority of prior developmental research on ToM has used behavioral methods to describe milestones in theory of mind acquisition in early childhood. The experiments described in this thesis draw heavily from these two approaches, in order to link them: what is the relationship between the development of functionally selective responses in ToM brain regions, and developmental changes in ToM reasoning in childhood? Chapter 1 describes two longitudinal fMRI experiments that test for developmental change and stable individual differences in neural and behavioral measures of ToM, and for predictive relationships between the two measures. Chapter 2 describes a large, cross-sectional study that measures the development of the cortical dissociation between brain regions that process minds (the ToM network) and those that process bodies (the Pain Matrix). Chapter 2 additionally provides insight into the neural correlates of passing the false-belief task - the best known developmental milestone in ToM reasoning. Chapter 3 uses a publicly available dataset in order to provide confirmatory evidence for the results described in Chapter 2, and clarifies the relationship between stimulus-driven functional responses, and inter-region correlations within and between ToM and pain brain regions. Chapter 4 characterizes ToM development, neurally and behaviorally, in children who have experienced delayed access to sign language. Finally, Chapter 5 provides a discussion of challenges and strategies in developmental cognitive neuroscience research. This interdisciplinary thesis has three broad goals: 1) to characterize kinds of neural change that support and/or predict behavioral improvements in theory of mind, 2) to gain novel insight into the nature of specific behavioral milestones in social reasoning, and 3) to better understand the impact of experience (e.g., linguistic input) on ToM development, behaviorally and neurally. / by Hilary L. Richardson. / Ph. D. in Neuroscience

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2006. / Includes bibliographical references. / Introduction: This thesis contains two main projects that I worked on during my graduate studies at MIT. Both address the subject matter of how neurons communicate, process, and pass information within the context of larger neuronal ensembles. The first project focuses on information transfer between two neurons during synaptic transmission. The project was spurred by an initial observation that neuronal communication through synapses in young and developing neuronal networks is only "half-hearted" in that signals propagate predominantly through only one type of synaptic receptor (the NMDA receptor), and bypass the principal signaling pathway present in mature synaptic transmission (AMPA receptor) (Malenka and Nicoll 1997). The possible cause of this abnormality was either that AMPA receptors were lacking on the postsynaptic side, or that something else in the process of synaptic transmission rendered them inoperable. / by Boris Krupa. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1997. / Includes bibliographical references (p. 92-105). / by Bradley R. Postle. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2004. / Includes bibliographical references. / Ras is an evolutionally conserved signaling molecule that has been implicated in a variety of cellular events, such as cell proliferation, differentiation, and survival. Recent studies also suggest roles of Ras in neuronal plasticity. I investigated the role of Ras in associative learning and memory in Drosophila. Flies carrying hypomorphic ras mutations were impaired in memory, with normal learning performance. The severity of the memory impairment correlated with molecular lesions in the ras gene. Studies on synaptic morphology at larval neuromuscular junctions revealed an increased number of presynaptic varicosities in the ras mutants. Flies carrying a dominant-negative or -active form of a ras transgene showed a learning impairment, when expression of the transgene occurred in the mushroom bodies (MBs), the center for the associative learning and memory. Acute induction of dominant-active ras expression also resulted in a learning impairment. Simple sensorimotor functions and overall MB morphology were normal in all the flies that showed learning or memory impairments. These results collectively suggest a direct role of Ras signaling in associative learning and memory in Drosophila. / (cont.) Here, I also present the results of characterization of a strong eye phenotype resulting from inhibition of Ras signaling. When a dominant-negative form of mammalian ras was expressed in the eye imaginal disc, flies developed eyes that are severely reduced in size. The phenotype was modified in a way sensitive to the level of Ras signaling. It was based on massive cell death resulting from inhibition of EGFR/Ras-dependent signaling pathways, including the MAPK and PI3-K pathways. Additional components such as Amnesiac and Rap appeared to modulate the signaling machinery associated with the phenotype. Oncogenic ras has been implicated in many types of tumors. This Ras-associated small eye phenotype may provide a new powerful tool to help develop therapeutic strategies for human cancers, as well as further understand the complexity of Ras signaling in basic biological events. / by Toshimasa Sakamoto. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1990. / Title as it appears in the M.I.T. Graduate List: The acquisition ofverbal categories. / Includes bibliographical references (p. 267-276). / by Karin J. Stromswold. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1994. / Includes bibliographical references (leaves 130-139). / by Marvin Myungwoo Chun. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2013. / Cataloged from PDF version of thesis. / Includes bibliographical references. / This thesis demonstrates that chronic immobilization stress administered to rats enhances fear learning and increases plasma acylated ghrelin. This effect is independent of the hypothalamus-pituitary-adrenal (HPA) axis since it was unaffected by prior bilateral adrenalectomy. Chronic exposure to a ghrelin receptor agonist, without stress, enhanced associational fear learning without altering HPA hormone levels. This effect was replicated by repeated direct infusions of a ghrelin receptor agonist in the basolateral amygdala (BLA), a brain region involved in emotional memory and altered by stress, suggesting a direct action of ghrelin at ghrelin receptors in the BLA. Administration of a ghrelin receptor inverse-agonist concurrent with stress exposure prevented stress-induced enhancement of fear learning. Other forms of chronic stress increase plasma acylated ghrelin as well, suggesting ghrelin is a novel mediator of long-term stress and a causal agent for stress-increased fear. Furthermore, this thesis identifies patterns in stress-induced feeding changes and body weight alterations that may offer an etiological explanation of the recruitment of the ghrelin pathway during periods of chronic stress. The final scientific chapter of this thesis describes a non-pharmacological intervention to enhance extinction of learned fear. In this work, optimization of extinction training yields resistance to spontaneous recovery of fear and demonstrates a weakening of potentiated synapses in the amygdala after optimal, but not suboptimal, behavioral extinction training. / by Retsina Michele Meyer. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2008. / 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. 197-216). / Human learners routinely make inductive inferences, or inferences that go beyond the data they have observed. Inferences like these must be supported by constraints, some of which are innate, although others are almost certainly learned. This thesis presents a hierarchical Bayesian framework that helps to explain the nature, use and acquisition of inductive constraints. Hierarchical Bayesian models include multiple levels of abstraction, and the representations at the upper levels place constraints on the representations at the lower levels. The probabilistic nature of these models allows them to make statistical inferences at multiple levels of abstraction. In particular, they show how knowledge can be acquired at levels quite remote from the data of experience--levels where the representations learned are naturally described as inductive constraints. Hierarchical Bayesian models can address inductive problems from many domains but this thesis focuses on models that address three aspects of high-level cognition. The first model is sensitive to patterns of feature variability, and acquires constraints similar to the shape bias in word learning. The second model acquires causal schemata--systems of abstract causal knowledge that allow learners to discover causal relationships given very sparse data. The final model discovers the structural form of a domain--for instance, it discovers whether the relationships between a set of entities are best described by a tree, a chain, a ring, or some other kind of representation. The hierarchical Bayesian approach captures several principles that go beyond traditional formulations of learning theory. / (cont.) It supports learning at multiple levels of abstraction, it handles structured representations, and it helps to explain how learning can succeed given sparse and noisy data. Principles like these are needed to explain how humans acquire rich systems of knowledge, and hierarchical Bayesian models point the way towards a modern learning theory that is better able to capture the sophistication of human learning. / by Charles Kemp. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2001. / Vita. / Includes bibliographical references (leaves 153-180). / Long term potentiation (LTP) of synaptic transmission at the CA3-CA1 hippocampal synapse is a model synaptic plasticity mechanism that may underlie hippocampal dependent learning and memory. Inhibition of post-synaptic calcium/calmodulin protein kinase II (CaMKII) has been shown to block LTP, and a global knockout of the highly expressed a isoform of CaMKII caused an impairment in LTP and hippocampus dependent learning. We examined the role of CaMKII in CA3-CA1 LTP by selectively deleting [alpha]-CaMKII in adult hippocampal CA1 or CA3 pyramidal cells using conditional gene targeting. With this approach, we could investigate the locus of change that underlies LTP expression, as both pre- (CA3) and post- (CA1) synaptic CaMKII dependent mechanisms have been implicated, and further examine how CaMKII dependent plasticity contributes to learning and memory in a background of normal brain development. CA3-CA1 LTP is reduced in CA1 [alpha]-CaMKII knockout mice, suggesting that post-synaptic CaMKII is required for normal LTP. These mice are strikingly reminiscent of the a-CaMKII global knockout mice, demonstrating comparable LTP impairments and abnormal behaviors. In contrast, CA3 [alpha]-CaMKII knockout mice have normal LTP at CA3-CA1 synapses, suggesting that CaMKII phosphorylation of pre-synaptic synapsin I is not required for LTP expression. Contextual and cued fear conditioning were also normal in CA3 mutants, demonstrating that one form of hippocampus dependent learning is intact. / (cont.) While several pre-synaptic short term plasticity mechanisms were unaffected in CA3 [alpha]-CaMKII knockout mice, repetitive stimulation protocols using short trains of stimuli of increasing frequency revealed enhanced frequency facilitation in mutants compared with controls. This suggests that CaMKII may be acting pre-synaptically as a negative regulator of neurotransmitter release during certain repetitive stimulation conditions, and as a "frequency detector" of calcium spikes, reaching higher levels of activation with increasing frequency of stimulation. Modulation of facilitation could be important to prevent synaptic terminals from depleting their vesicle stores during episodes of repetitive firing, or to maintain synaptic activity in an optimal range for information coding. / by Heather L. Hinds. / Ph.D.