How much variability is there in normal, healthy brains, and when do variations in specific circuit components result in the circuit dysregulation that is thought responsible for many psychiatric and neurological disorders? These questions will be studied in a small motor circuit, the crustacean stomatogastric ganglion, in which it is possible to identify and record from all of the circuit neurons. The variability in the expression f genes for voltage-dependent ion channels and receptors will be measured in every identified cell type in the circuit, and correlations among them explored. Channel and receptor gene expression will be compared across cells, and between somata and the neuropil. Voltage-clamp experiments will be used to determine whether membrane currents correlate with the expression of the genes thought to encode the proteins responsible for those currents. Channel and receptor correlations in specific identified neurons will be studied subsequent to perturbations by temperature acclimation and removal of neuromodulatory inputs. Finally, a large data base of motor patterns will be created, analyzed, and made available to allow the study of variability of motor patterns and their response to perturbation across thousands of healthy animals.
The brain of every human being is different. To understand the differences between normal healthy brain, and those of individuals with psychiatric or neurological disorders, it is necessary to understand how much variability in circuit properties is consistent with 'good enough' circuit performance, and when changes in a specific circuit function will produce dysfunction. We will study this problem by measuring the ranges of specific circuit molecules in single neurons, across animals, under control conditions and in response to strong perturbations that can lead to circuit dysregulation.
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