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Biomedical subjects

Rachel Chen

Publications and source records attributed to Rachel Chen.

3 recordsLinked to original sources

Complementation testing identifies genes mediating effects at quantitative trait loci underlying fear-related behavior.

Knowing the genes involved in quantitative traits provides an entry point to understanding the biological bases of behavior, but there are very few examples where the pathway from genetic locus to behavioral change is known. To explore the role of specific genes in fear behavior, we mapped three fear-related traits, tested fourteen genes at six quantitative trait loci (QTLs) by quantitative complementation, and identified six genes. Four genes, Lamp, Ptprd, Nptx2, and Sh3gl, have known roles in synapse function; the fifth, Psip1, was not previously implicated in behavior; and the sixth is a long non-coding RNA, 4933413L06Rik, of unknown function. Variation in transcriptome and epigenetic modalities occurred preferentially in excitatory neurons, suggesting that genetic variation is more permissible in excitatory than inhibitory neuronal circuits. Our results relieve a bottleneck in using genetic mapping of QTLs to uncover biology underlying behavior and prompt a reconsideration of expected relationships between genetic and functional variation.

Animals↗

Increased neuronal excitability, synaptic plasticity, and learning in aged Kvbeta1.1 knockout mice.

BACKGROUND: Advancing age is typically accompanied by deficits in learning and memory. These deficits occur independently of overt pathology and are often considered to be a part of "normal aging." At the neuronal level, normal aging is known to be associated with numerous cellular and molecular changes, which include a pronounced decrease in neuronal excitability and an altered induction in the threshold for synaptic plasticity. Because both of these mechanisms (neuronal excitability and synaptic plasticity) have been implicated as putative cellular substrates for learning and memory, it is reasonable to propose that age-related changes in these mechanisms may contribute to the general cognitive decline that occurs during aging. RESULTS: To further investigate the relationship between aging, learning and memory, neuronal excitability, and synaptic plasticity, we have carried out experiments with aged mice that lack the auxiliary potassium channel subunit Kvbeta1.1. In aged mice, the deletion of the auxiliary potassium channel subunit Kvbeta1.1 resulted in increased neuronal excitability, as measured by a decrease in the post-burst afterhyperpolarization. In addition, long-term potentiation (LTP) was more readily induced in aged Kvbeta1.1 knockout mice. Finally, the aged Kvbeta1.1 mutants outperformed age-matched controls in the hidden-platform version of the Morris water maze. Interestingly, the enhancements in excitability and learning were both sensitive to genetic background: The enhanced learning was only observed in a genetic background in which the mutants exhibited increased neuronal excitability. CONCLUSIONS: Neuronal excitability is an important determinant of both synaptic plasticity and learning in aged subjects.

Action Potentials↗

Characterization of polar organic compounds in the organic film on indoor and outdoor glass windows.

Organic films on an impervious surface (window glass) were sampled at paired indoor-outdoor sites in July 2000 and characterized for their paraffinic and polar organic compositions along an urban-rural transect. Four classes of polar compounds (C11-C31 aliphatic monocarboxylic, C6-C14 dicarboxylic, nine aromatic polycarboxylic, and five terpenoid acids) constituted between 81 and 95% (w/w) of the total organic fraction analyzed comprising n-alkanes (C10-C36), 46 PAH, 97 PCBs, and 18 OC pesticides. Concentrations of the polar compounds plus their precursors, n-alkanes, ranged from 8 to 124 microg m(-20 and were dominated by monocarboxylic acids (67-89%, w/w). On outdoor windows, n-alkanes, aromatic acids, and terpenoid acids decreased in concentration along the urban-rural transect. The carbon preference index values and the interpretations of individual compounds indicate that the main sources of n-alkanes were plant waxes followed by petrogenic sources; monocarboxylic and dicarboxylic acids were from plant waxes and animal fats. Results of principal component analysis showed closer correspondence between outdoor and indoor signatures than among locations. In outdoor films, these compounds are suggested to play an important role in mediating chemical fate in urban areas by air-film exchange and facilitating "wash-off" due to their surfactant-like properties. In indoor films, these compounds provide a medium for the accumulation of more toxic compounds.

Air Pollutants↗