The Gatsby Charitable Foundation
The Foundation makes grants for charitable activity which it hopes may make life better for people, especially those who are disadvantaged. For details on Columbia’s Gatsby Initiative click here.
Columbia Award Recipients
Gatsby Initiative Pilot Project Summaries (February 1, 2008)
Balan, Puiu F, Ph.D.
“Neural basis of categorization and generalization in the prefrontal and parietal cortex”
Adaptation to a complex environment requires something beyond simple inventory of stimulus-response associations. It is known that monkeys, like humans, can detect common characteristics of events and store related events as categories. This ability for categorization may be critical for adaptive behavior by allowing organisms to generalize – that is, to rapidly evaluate the category membership of novel events, and use this evaluation to guide behavioral decisions. Categorization-related activity has been described in monkey prefrontal (PFC) and posterior parietal (PPC) cortices. However, it is not known whether and how these responses are functionally related to behavioral measures of categorization and whether they allow monkeys to generalize behavioral policies from familiar to novel exemplars. The experiments proposed here address these questions using a combination of behavioral training, computational modeling and simultaneous multi-neural recordings in PFC and PPC.
Bruno, Randy M., Ph.D.
“Determining the number and spatial distribution of thalamocortical synapses onto cortical neurons”
Sensory stimuli elicit robust cortical responses, which are initiated by the thalamocortical (TC) projection. On the basis of in vitro physiology experiments, it has been inferred that individual TC afferents establish many more synaptic contacts onto a post-synaptic cortical neuron than individual corticocortical axons do, explaining observations of greater TC efficacy. This innervation density hypothesis has, however, recently been called into question. Furthermore, other factors, such as the spatial organization of TC synapses and their electrotonic distances to the soma, may contribute to TC axons having greater efficacy than corticocortical axons. Current anatomical methods for identifying synapses arising from a pre-synaptic neuron (or population) onto a specific post-synaptic cell have significant limitations and are prohibitively timeconsuming. I propose to develop a faster, more comprehensive approach for determining the number and spatial distribution of various synaptic sources onto an individual post-synaptic cell. This method will be applied to individual TC connections to test both the innervation density and spatial organization hypotheses.
Fusi, Stefano, Ph.D. and Hen, René, Ph.D.
“A model of hippocampal neurogenesis to explain the novelty-detection paradox”
Since antidepressants exert their action through neurogenesis2, an investigation of the functional implications of neurogenesis could improve our understanding of depression, a profound mood disorder affecting as much as 16% of the U.S. population3. Overall, recent theoretical models of neurogenesis confirm observations that certain hippocampus-dependent behavioral measures improve with increased neurogenesis4. However, the laboratory of our coinvestigator has demonstrated behavioral paradoxes resulting from neurogenesis. For example, some hippocampus-dependent behaviors actually improve with the ablation of neurogenesis, including novelty detection5 and working memory interference6. Additionally, new neurons have unique cellular properties that have not been taken into account in prior models, including greater excitability and greater plasticity, relative to their mature counterparts4. Therefore, we propose a computational model of neurogenesis constrained by our experimental evidence for the behavioral costs and benefits of neurogenesis that will include the unique cellular characteristics of adult-born granule cells. This project is a collaboration between the laboratories of Assistant Professor Stefano Fusi and Professor Rene Hen.
"Characterization of the neuronal circuitry controlling locomotion in Drosophila"
Animal locomotion is in part dependent on central pattern generators (CPGs), which can produce rhythmic outputs of neuronal activity without input from higher centers in the brain. In general, however, the cellular basis of CPGs has not been defined. In an effort to characterize the neuronal circuitry underlying the coordination of walking in the adult fruit fly, we propose to map the motor neurons and interneurons that are required for locomotion. To accomplish this goal, we have developed a two-component transgenic expression system that allows the expression of markers or other transgenes in well-defined subsets of motor neurons and interneurons. Using this system, we will identify the subset of neurons required for leg movement in Drosophila. This approach provides a potentially powerful alternative to methods for mapping neuronal circuits that depend on the synaptic transfer of proteins, such as wheat germ agglutinin, between neurons.
Moore, Holly, Ph.D.
“Remodeling of Prefrontal Cortical-Amygdalar Circuits During Adolescence”
Abnormal function of the prefrontal cortical (PFC) and anteriomedial temporal lobe, including the amygdala (AMYG), has been implicated in affective and social deficits (negative symptoms) in schizophrenia and other psychiatric disorders.
Moreover, these structures have been shown in experimental animals to mediate affective behaviors that are relevant to these disorders (1). Importantly, emerging data suggests that PFC-AMYG circuits remodel during adolescence (2-3), a
period during or after which the affective and social deficits common to schizophrenia-related disorders emerge. Our laboratory has novel data showing that pruning of medial (m)PFC afferents to the AMYG occurs between adolescence and adulthood. Our findings are consistent with studies that suggest that pruning and increased specificity of inputs are key features of the maturation of the prefrontal and temporal cortex occuring as late as adolescence (4,5). However, how such “pruning” affects the innervation pattern and the function of limbic circuits remains unknown. The proposed studies will determine if the apparent pruning of the mPFC axons from the AMYG serves to enhance the topographical specificity of mPFC innervation and/or select specific sub-populations of neurons within the AMYG for long-term synaptic connectivity with mPFC afferents.
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Gatsby Initiative Pilot Project Summaries
