Faculty Bibliography

Deep cerebral venous thrombosis is often a devastating condition associated with hemorrhagic infarction. We describe a patient who presented with acute micrographia and hypophonia as the sole manifestations of extensive deep venous sinus thrombosis

The relevance of gamma band oscillatory frequency (25-60Hz) in neuronal activity has been explored in contexts ranging from single cell recording to EEG and MEG. If activity in specific frequency bands is associated with the functional activation of each hemisphere (e.g. phonetic segmentation in the left versus prosodic analysis in the right), then the relevant frequency bands might be differentially salient in the two hemispheres during different functional states. Recent studies suggest that left regions are specialized for rapid temporal processing. We tested this hypothesis by performing EEG and MEG recordings during the presentation of auditory stimuli of varying spectral complexity, including speech and ripples (dynamic broadband stimuli). Ripples were constructed to approximate spectral and temporal aspects of speech. Whole-head MEG (Magnes 2500, 4D-Neuroimaging) and high-density EEG (ESI-128, Neuroscan Inc.) were used to acquire auditory evoked responses. Spectral analysis techniques provided estimates of the relevant frequency responses. High-frequency responses were robustly different for left and right regions, with gamma activity (25-60Hz) being more pronounced in left temporal cortex. The effect was observed in EEG and MEG recordings, and for both stimulus types. The data are consistent with the view that sensory input is recorded in specific frequency bands and on different time-scales by the two hemispheres, depending on the nature of the sensory input

Two-photon microscopy imaging was obtained from mammalian Purkinje cells in acute cerebellar slices using calcium green 1. Patch-clamp recordings demonstrated the expected ionic currents in response to glutamate iontophoresis directly onto the dendrites. This response was accompanied by an increase in transmembrane calcium influx as determined by the two-photon imaging of calcium green fluorescence. Furthermore, under these conditions both climbing and parallel fiber evoked synaptic currents were reduced in amplitude in accordance with the concept of long-term depression (LTD). However, glutamic iontophoresis also produced concomitant with LTD a swelling of the targeted dendrites. The increase in diameter was particularly clear in dendritic branchlets, as well as at dendritic bifucation points. Similar swelling responses were also obtained with high frequency activation of climbing fibers (i.e. higher than 10 Hz) indicating that the response could also be obtained following synaptic activation. The images were obtained at 5 min. intervals and demonstrated that the swelling could occur within a few minutes. Light and ultrastructural studies of slices, using calbinding staining in the presence and absence of calcium green dye injection, demonstrated that Purkinje cell dendritic swelling was mostly restricted to intracellular compartments, leaving the cytosol more or less intact. These results indicate that LTD may serve as a neuroprotective mechanism, reducing the likelihood of excitotoxicity by reducing glutamic responsiveness

Thalamocortical dysrhythmia (TCD) is a pathophysiological event postulated to underlie a range of neuropsychiatric disorders, including neurogenic pain (NP), tinnitus, Parkinson's disease, major depression, OCD and some forms of epilepsy. Patients suffering from this syndrome exhibit chronic and excessive theta (4-8 Hz) rhythmicity and increased coherence between high- and low-frequency thalamocortical oscillations. (Llinas et al, PNAS 1999) To determine the possibility of distinguishing between pain symptoms which emanate from TCD and those which derive from nociceptive activation, MEG was used to record 5 minutes of spontaneous brain activity from patients obtaining relief from epidural spinal cord stimulation (SCS), patients who failed SCS, patients with mild NP not requiring SCS and normal controls at baseline and during thermal (cold) pain stimulation. Analysis of patients who failed SCS showed significant increases in theta/alpha (8-12 Hz) power ratios and spectral amplitudes, together with abnormal levels of coherence between amplitudes at different frequencies. In contrast, there were no significant differences in spectral properties or coherence between controls and remaining patients or between baseline and thermal pain states in controls. These findings indicate that chronic pain may be generated either by TCD or via continuous nociceptive input, and that each has distinct mechanisms for its generation and responds to different therapeutic interventions. Thus, SCS is successful in peripheral pain but fails in NP

P.A. Rhodes1,2* and R. Llinas2, 1MRB, NIDDK, NIH, Bethesda, MD 20814; 2Dept. Physiology and Neuroscience, NYU Medical School, New York, NY 10016. The complexities of mammalian 6-layered neocortex make elucidation of its basic functions a daunting challenge. One seeks a model system which reflects its fundamental neural operations but with a simpler set of elements. We offer here an analysis supporting the conjecture that the cortex of the turtle pseudomys scripta provides a suitable model system. Principal cell dendritic morphology, intrinsic firing properties, spine form and distribution, feedforward inhibitory physiology, ACh and NE innervation, the laminar organization of corticocortical association, and many other features are common between turtle and mammalian neocortex, along with piriform cortex and dentate gyrus. One implication of the proposed homology concerns the nature of layer 1 input. In turtle cortex layer 1 conveys the feedforward relay, both from sensory thalamus and the corticocortical feedforward projection (Desan 1984). In mammalian piriform cortex and dentate gyrus layer 1 also conveys the feedforward relay of sensory information. In mammalian neocortex, however, layer 1 conveys inputs from higher to lower cortical areas, and so has heretofore been considered a secondary projection, modulating rather than driving cortical activity. The analogy with turtle cortex suggests an alternative view: neocortical layer 1, which appears to be quite effective in triggering layer 5 cell firing (Cauller and Connors 1992; Rhodes and Llinas 1999), may be a direct driver of cortical activity, with a role analogous to sensory input

The GTPase dynamin I is required for synaptic vesicle (SV) endocytosis. Our observation that dynamin binds to the SV protein synaptophysin in a Ca2+-dependent fashion suggested the possibility that a dynamin/synaptophysin complex functions in SV recycling. Here we show that disruption of the dynamin/synaptophysin interaction by peptide injection into the squid giant synapse preterminal results in a decrease in transmitter release during high-frequency stimulation, indicating an inhibition of SV recycling. Electron microscopy of these synapses reveals a depletion of SVs, demonstrating a block of vesicle retrieval after fusion. In addition, we observed an increase in clathrin-coated vesicles, indicating that the peptide does not block clathrin-dependent endocytosis. We conclude that the dynamin/synaptophysin complex functions in a clathrin-independent mechanism of SV endocytosis that is activated by the high Ca2+ concentration at SV release sites