Behavioral and electrophysiological abnormalities in two rat models of antiretroviral drug-induced neuropathy.

Painful peripheral neuropathy due to the antiretroviral therapy used to treat HIV is one of the most prevalent side effects occurring in at least 30% of patients living with this infection. We have evaluated the electrophysiological and behavioral effects of d4T and ddC on peripheral large and small nerve fibers in male rats treated with d4T (Sprague-Dawley, 50 mg/kg, twice within 1 week), ddC (Wistar, 50 mg/kg, 3 times per week for 3 weeks), or vehicle. The effect of the interventions was assessed using behavioral measures of mechanical sensitivity, conventional nerve conduction studies, and microneurographic single nerve C-fiber recordings.

Levetiracetam accelerates the onset of supply rate depression in synaptic vesicle trafficking.

Objective: To determine if levetiracetam (LEV) enhances the impact in excitatory presynaptic terminals of a rate-limiting mechanism in vesicle trafficking termed supply rate depression that emerges to limit synaptic transmission during heavy, epileptiform use.

Methods: The effect of LEV was measured with electrophysiologic assays of monosynaptic connections in ex vivo hippocampal slices from wild-type and synapsin knockout mice, and in primary cell culture neurons from wild-type and synaptic vesicle glycoprotein 2a (SV2a) knockout mice.

Results: LEV enhanced the impact of supply rate depression at Schaffer collateral synapses by shortening the time course for induction.

A new kinetic framework for synaptic vesicle trafficking tested in synapsin knock-outs.

At least two rate-limiting mechanisms in vesicle trafficking operate at mouse Schaffer collateral synapses, but their molecular/physical identities are unknown. The first mechanism determines the baseline rate at which reserve vesicles are supplied to a readily releasable pool. The second causes the supply rate to depress threefold when synaptic transmission is driven hard for extended periods.

Spontaneous electrical activity and behavior in the leech hirudo medicinalis.

In the absence of external stimuli, animals explore the environment by performing irregular movements, but the neuronal mechanisms underlying this arrhythmic motion are largely unknown. In this paper, we studied the relationship between the spontaneous neuronal activity in the leech (Hirudo medicinalis) and its behavior. We analyzed the electrical activity of isolated ganglia, chains of two connected ganglia, and semi-intact preparations.

Kinetic isolation of a slowly recovering component of short-term depression during exhaustive use at excitatory hippocampal synapses.

This study examines the kinetics of the longest lasting form of short-term depression at excitatory hippocampal synapses. After initial depletion of the readily releasable pool (RRP), continued 20-Hz stimulation was found to be fast enough to maximally drive presynaptic neurotransmitter exocytosis; maximal is defined here as the rate needed to maintain the RRP in a nearly empty steady state. Induction of depression proceeded in two distinct phases.

Augmentation controls the fast rebound from depression at excitatory hippocampal synapses.

Short-term plasticity occurs at most central chemical synapses and includes both positive and negative components, but the principles governing interaction between components are largely unknown. The residual Ca(2+) that persists in presynaptic terminals for several seconds after repetitive use is known to enhance neurotransmitter release under artificial, low probability of release conditions where depression is absent; this is termed augmentation. However, the full impact of augmentation under standard conditions at synapses where depression dominates is not known because of possibly complicated convolution with a variety of potential depression mechanisms.

On the dynamics of the spontaneous activity in neuronal networks.

Most neuronal networks, even in the absence of external stimuli, produce spontaneous bursts of spikes separated by periods of reduced activity. The origin and functional role of these neuronal events are still unclear. The present work shows that the spontaneous activity of two very different networks, intact leech ganglia and dissociated cultures of rat hippocampal neurons, share several features.

Statistics of decision making in the leech.

Animals continuously decide among different behaviors, but, even in invertebrates, the mechanisms underlying choice and decision are unknown. In this article, leech spontaneous behavior was tracked and quantified for up to 12 h. We obtained a statistical characterization, in space and time domains, of the decision processes underlying selection of behavior in the leech.

Quantitative characterization and classification of leech behavior.

This paper describes an automatic system for the analysis and classification of leech behavior. Three colored beads were attached to the dorsal side of a free moving or pinned leech, and color CCD camera images were taken of the animal. The leech was restrained to moving in a small tank or petri dish, where the water level can be varied.

Dynamics and reproducibility of a moderately complex sensory-motor response in the medicinal leech.

Local bending, a motor response caused by mechanical stimulation of the leech skin, has been shown to be remarkably reproducible, in its initial phase, despite the highly variable firing of motoneurons sustaining it. In this work, the reproducibility of local bending was further analyzed by monitoring it over a longer period of time and by using more intact preparations, in which muscle activation in an entire body segment was studied. Our experiments showed that local bending is a moderately complex motor response, composed of a sequence of four different phases, which were consistently identified in all leeches.

Synaptic integration in electrically coupled neurons.

Interactions among chemical and electrical synapses regulate the patterns of electrical activity of vertebrate and invertebrate neurons. In this investigation we studied how electrical coupling influences the integration of excitatory postsynaptic potentials (EPSPs). Pairs of Retzius neurons of the leech are coupled by a nonrectifying electrical synapse by which chemically induced synaptic currents flow from one neuron to the other.