Faculty Bibliography

BACKGROUND: Fibers containing galanin (GAL) enlarge and hyperinnervate cholinergic basal forebrain (CBF) nucleus basalis (NB) neurons in late-stage Alzheimer's disease (AD), yet the physiological consequences of this phenomenon are unclear. OBJECTIVE: To determine whether GAL hyperinnervation of cholinergic NB neurons modulates the expression of genes critical to cholinergic transmission [e.g. acetylcholine (ACh) metabolism and ACh receptors] in AD. METHODS: Single-cell gene expression profiling was used to compare cholinergic mRNA levels in non-GAL-hyperinnervated NB neurons in tissue autopsied from cases classified as having no cognitive impairment (NCI) or late-stage AD (AD/GAL-) and in GAL-hyperinnervated (AD/GAL+) NB neurons from the same AD subjects. RESULTS: AD/GAL+ cells displayed a significant upregulation in choline acetyltransferase (ChAT) mRNA expression compared to NCI and AD/GAL- cells. CONCLUSION: GAL fiber hyperinnervation of cholinergic NB neurons upregulates the expression of ChAT, the synthetic enzyme for ACh, suggesting that GAL regulates the cholinergic tone of CBF neurons in AD

We consider the problem of transforming a signal to a representation in which the components are statistically independent. When the signal is generated as a linear transformation of independent Gaussian or non-Gaussian sources, the solution may be computed using a linear transformation (PCA or ICA, respectively). Here, we consider a complementary case, in which the source is non-Gaussian but elliptically symmetric. Such a source cannot be decomposed into independent components using a linear transform, but we show that a simple nonlinear transformation, which we call radial Gaussianization (RG), is able to remove all dependencies. We apply this methodology to natural signals, demonstrating that the joint distributions of nearby bandpass filter responses, for both sounds and images, are closer to being elliptically symmetric than linearly transformed factorial sources. Consistent with this, we demonstrate that the reduction in dependency achieved by applying RG to either pairs or blocks of bandpass filter responses is significantly greater than that achieved by PCA or ICA.