Faculty Bibliography

Increases in intracellular calcium concentration are required for the release of neurotransmitter from presynaptic terminals in all neurons. However, the mechanism by which calcium exerts its effect is not known. A low-sensitivity calcium-dependent photoprotein (n-aequorin-J) was injected into the presynaptic terminal of the giant squid synapse to selectively detect high calcium concentration microdomains. During transmitter release, light emission occurred at specific points or quantum emission domains that remained in the same place during protracted stimulation. Intracellular calcium concentration microdomains on the order of 200 to 300 micromolar occur against the cytoplasmic surface of the plasmalemma during transmitter secretion, supporting the view that the synaptic vesicular fusion responsible for transmitter release is triggered by the activation of a low-affinity calcium-binding site at the active zone

A potential specific to no-go reaction in go/no-go reaction time hand movement with discrimination between different colour light stimuli was recorded in the dorsal bank of the principal sulcus and the rostroventral corner of the prefrontal cortex of the both hemispheres in monkeys, called 'no-go potential'. The potential is composed of surface-negative, depth-positive deflections in the cortex at a latency of 85-150 ms from the onset of no-go visual stimulus. Behavioural and electrophysiological studies demonstrated that the no-go potential is related to decision or judgement not to move and to subsequent suppression of movement execution. The same kind of negative potential could be recorded from the human scalp on the same discriminative motor task. It spreads to both sides of the frontal region with its maximum in the vertex (Fz). Magneto-encephalographic studies suggested that electrical dipoles exist in the dorsolateral parts of the both cerebral hemispheres on the no-go reaction of the discrimination task using either hand

This article introduces a new experimental paradigm for the study of temporal lobe epilepsy. This approach utilizes the isolated guinea pig brain in vitro preparation, which generates a pattern of hypersynchronous neuronal activity similar to the peculiar 8-30 Hz rhythm characterizing stereoelectroencephalographic hippocampal recordings in human temporal lobe epilepsy. The present report describes an attempt to identify the functional events underlying the epileptiform activities observed in this preparation. Rhythmic epileptiform discharges (EDs), here defined as population spikes (PSs) recorded from somata or dendritic layers, were induced in the hippocampal formation of the isolated guinea pig brain maintained in vitro by tetanic stimulation of the entorhinal cortex (EC). Two patterns of EDs were distinguished by performing simultaneous field potential recordings along the dentate gyrus (DG), EC, CA1, and CA3. During stage 1, the first self-sustained EDs were isolated PSs occurring at a frequency of 2-3 Hz at all levels of the entorhinal-hippocampal loop, the only exception being the DG, where no signs of synchronized neuronal discharge could be found. Over the next 30-50 sec, the temporal organization of these EDs changed dramatically. During stage 2, at all levels of the entorhinal-hippocampal loop, EDs occurred in 0.3-0.5 sec trains of 16-25 Hz population spikes interrupted by 0.7-1.3 sec silent periods. The transition between stages 1 and 2 coincided with the occurrence of population spikes in the DG. Laminar analyses and multiple simultaneous field potential recordings revealed that the trains of EDs observed in stage 2 resulted from the repetitive, sequential activation of the hippocampal-entorhinal loop. In the transverse axis, the earliest event usually occurred in the CA3 region. Thereafter, population spikes occurred sequentially in the CA1 region, EC, DG, and back to the CA3 region. Intracellular recordings confirmed that the EDs recorded extracellularly resulted from the synchronous activation of the cells in phase with the locally recorded field potentials. Dentate granule cells, layer II entorhinal cells, as well as CA1 pyramids displayed large-amplitude EPSPs crowned by an isolated action potential phase locked to the locally recorded field potential. In contrast, the activity of CA3 pyramids consisted of typical paroxysmal depolarization shifts on which bursts of action potentials of decreasing amplitude were observed. These results suggest that reentrant loop activity in the hippocampal-entorhinal circuit represents the central event in the functional organization of hippocampal epileptic discharges

We have studied the effect of the purified toxin from the funnel-web spider venom (FTX) and its synthetic analog (sFTX) on transmitter release and presynaptic currents at the mouse neuromuscular junction. FTX specifically blocks the omega-conotoxin- and dihydropyridine-insensitive P-type voltage-dependent Ca2+ channel (VDCC) in cerebellar Purkinje cells. Mammalian neuromuscular transmission, which is insensitive to N- or L-type Ca2+ channel blockers, was effectively abolished by FTX and sFTX. These substances blocked the muscle contraction and the neurotransmitter release evoked by nerve stimulation. Moreover, presynaptic Ca2+ currents recorded extracellularly from the interior of the perineural sheaths of nerves innervating the mouse levator auris muscle were specifically blocked by both natural toxin and synthetic analogue. In a parallel set of experiments, K(+)-induced Ca45 uptake by brain synaptosomes was also shown to be blocked or greatly diminished by FTX and sFTX. These results indicate that the predominant VDCC in the motor nerve terminals, and possibly in a significant percentage of brain synapses, is the P-type channel