Faculty Bibliography

Local hemodynamics of the cerebral cortex is the basis of modern functional imaging techniques, such as fMRIand PET. Despite the importance of local regulation of the blood flow, capillary level quantification of cerebral blood flow has been limited by the spatial resolution of functional imaging techniques and the depth penetration of conventional optical microscopy. Two-photon laser scanning microscopic imaging technique has the necessary spatial resolution and can image capillaries in the depth of the cortex. We have loaded the serum with fluorescein isothiocyanate dextran and quantified the flow of red blood cells (RBCs) in capillaries in layers 2/3 of the mouse somatosensory cortex in vivo. Basal capillary flux was quantified as approximately 28.9+/-13.6 RBCs/s (n=50, mean+/-S.D.) under ketamine-xylazine anesthesia and 26.7+/-16.0 RBCs/s (n=31) under urethane anesthesia. Focal interictal (epileptiform) activity was induced by local infusion of bicuculline methochloride in the cortex. We have observed that capillary blood flow increased as the cortical local field events developed into epileptiform in the vicinity of GABA receptor blockade (<300 microm from the administration site). Local blood flow in the interictal focus increased significantly (42.5+/-18.5RBCs/s, n=52) relative to the control conditions or to blood flow measured in capillaries at distant (>1mm from the focus) sites from the epileptic focus (27.8+/-12.9 RBCs/s, n=30). These results show that hyper-synchronized neural activity is associated with increased capillary perfusion in a localized cortical area. This volume is significantly smaller than the currently available resolution of the fMRI signal

Neuroleptics are generally highly effective in suppressing tics, but their many adverse effects limit their usefulness. Animal studies have shown that, compared with both typical and atypical neuroleptics, metoclopramide has effects that are regionally circumscribed to rat motor striatum. Based on this observation and two prior case reports, metoclopramide was openly prescribed and individually titrated to diminish tics in 10 patients with Tourette syndrome. All patients improved on the Yale Global Tic Severity Scale by an average of 55%. Although we did not observe frank extrapyramidal symptoms, including tardive dyskinesia, these data are not sufficient to support clinical recommendations because of many limitations, including the absence of systematic ratings of nontic abnormal movements. However, controlled clinical studies and additional basic investigations of metoclopramide are warranted

With the recent explosion in the characterization of different sensory systems, a general rule is emerging: only one type of sensory receptor molecule is expressed per receptor neuron. The visual system is no exception and, in most cases, photoreceptors express only one visual pigment per cell. However, the mechanisms underlying the exclusion of sensory receptors are poorly understood. As expression of a given receptor in a given cell is often stochastic, a decision must first be made to express one of the many receptors of the same family (i.e. one particular rhodopsin) and this expression must correlate with the silencing of the other receptors. Furthermore, the projection center for the receptors in the brain must be informed of the decision in order to process this information. Although cells can choose from up to hundreds of sensory receptors (e.g. in the olfactory system), they make almost no mistakes. Evidence has recently emerged that the exclusion mechanism involves the sensory receptor molecules themselves. Here, we describe the findings from various systems in mammals and Drosophila, and review evidence that in the simple visual system of the fly, rhodopsin molecules play an important role in sensory receptor exclusion.