Neural analogs of associative learning in {\it Aplysia\/}: Experimental and theoretical approaches

A change in synaptic strength arising from the activation of two neuronal pathways at approximately the same time is a form of associative plasticity and may underlie classical conditioning. Previously, a cellular analog of a classical conditioning protocol has been demonstrated to produce short-term associative plasticity at the connections between sensory and motor neurons in Aplysia. A similar training protocol produced long-term (24 hour) enhancement of excitatory postsynaptic potentials (EPSPs). EPSPs produced by sensory neurons in which activity was paired with a reinforcing stimulus were significantly larger than unpaired controls 24 hours after training. To examined whether the associative plasticity observed at these synapses may be involved in higher-order forms of classical conditioning, a neural analog of contingency was developed. In addition, computer simulations were used to analyze whether the associative plasticity observed in Aplysia could, in theory, account for second-order conditioning and blocking. ^

Theoretical and experimental studies of linkage disequilibrium in human populations

Linkage disequilibrium (LD) is defined as the nonrandom association of alleles at two or more loci in a population and may be a useful tool in a diverse array of applications including disease gene mapping, elucidating the demographic history of populations, and testing hypotheses of human evolution. However, the successful application of LD-based approaches to pertinent genetic questions is hampered by a lack of understanding about the forces that mediate the genome-wide distribution of LD within and between human populations. Delineating the genomic patterns of LD is a complex task that will require interdisciplinary research that transcends traditional scientific boundaries. The research presented in this dissertation is predicated upon the need for interdisciplinary studies and both theoretical and experimental projects were pursued. In the theoretical studies, I have investigated the effect of genotyping errors and SNP identification strategies on estimates of LD. The primary importance of these two chapters is that they provide important insights and guidance for the design of future empirical LD studies. Furthermore, I analyzed the allele frequency distribution of 26,530 single nucleotide polymorphisms (SNPs) in three populations and generated the first-generation natural selection map of the human genome, which will be an important resource for explaining and understanding genomic patterns of LD. Finally, in the experimental study, I describe a novel and simple, low-cost, and high-throughput SNP genotyping method. The theoretical analyses and experimental tools developed in this dissertation will facilitate a more complete understanding of patterns of LD in human populations. ^