Spontaneous Synaptic Potentials

The spontaneous electrical activity of the brain can be measured by electroencephalography (EEG), a technique that has been widely employed to study neurotoxic effects of chemicals both in humans and in experimental animals. EEG waves represent summated synaptic potentials generated by the pyramidal cells of the cerebral cortex (Misra 1992). These potentials are the responses of cortical cells to rhythmical changes arising from thalamic nuclei. The signals recorded can be separated into frequency bands—faster waves exceeding 13 Hz, and slower ones below 4 Hz. 

Hirst You can easily see spontaneous synaptic potentials if you make long recordings from a non-pressurized arteriole. The clamps are big enough to see this property in situ. I have never seen a STOC in an arteriole or a piece of longitudinal muscle of the intestine unless I have applied a non-physiological stimulant. 

In electrophysiological studies aimed at elucidating the mechanism of action of kappa agonists, U-50488 has been shown to depress excitatory post-synaptic potentials in a rat locus coeruleus preparation, which indicates that it acts presynaptically to inhibit transmitter release [38]. Also, in spinal cord slice preparations from the 9-16-day-old rat, U-69593 (9) produced a naloxone-reversible depression of spontaneous and electrically evoked activity in dorsal horn neurones [39],... 

Secretory cells often release vesicles spontaneously at a low rate whereas release rates increase when a stimulus arrives at the release site. For example, miniature synaptic potentials represent spontaneous release from the neuronal presynaptic terminal (Katz, 1966 Stevens, 1993). In contrast, sperm have only one secretory vesicle and, as discussed previously, cells that complete the acrosome reaction prior to egg contact are infertile. This problem may be circumvented, in part, by the fact that large numbers of sperm are produced by mammals, thereby minimizing the consequences of premature acrosome reactions in large populations. However,... 

Tyrosine phosphorylation plays an important role in synaptic transmission and plasticity. Evidence for this role is that modulators of PTKs and PTPs have been shown to be intimately involved in these synaptic functions. Among the various modulators of PTKs, neuro-trophins have been extensively studied in this regard and will be our focus in the following discussion (for details of growth factors, see Ch. 27). BDNF and NT-3 have been shown to potentiate both the spontaneous miniature synaptic response and evoked synaptic transmission in Xenopus nerve-muscle cocultures. Neurotrophins have also been reported to augment excitatory synaptic transmission in central synapses. These effects of neurotrophins in the neuromuscular and central synapses are dependent on tyrosine kinase activities since they are inhibited by a tyrosine kinase inhibitor, K-252a. Many effects of neurotrophins on synaptic functions have been attributed to the enhancement of neurotransmitter release BDNF-induced increase in neurotransmitter release is a result of induced elevation in presynaptic cytosolic calcium. Accordingly, a presynaptic calcium-depen-dent phenomenon - paired pulse facilitation - is impaired in mice deficient in BDNF. 

The fact that most serotonergic dorsal raphe neurons are dependent on extrinsic excitatory or facilitatory inputs to express their characteristic spontaneous activity may seem to contradict previous studies suggesting that these neurons may function as autonomous pacemakers (42) with an endogenous rhythm (31) attributable to the presence of pacemaker potentials (8). Such a contradiction exists only if one insists that endogenous rhythms and pacemaker potentials must, by definition, be totally autonomous, i.e., completely independent of all extrinsic synaptic or neurohumoral influences. Such a definition would seem too restrictive in view of the fact that some invertebrate neurons display pacemaker potentials only when certain afferent fibers are stimulated (38) or when exposed to certain neurohumoral substances (18,28). 

Even in the absence of drug therapy, individual seizures are usually self-limiting. Brain neurons are unable to sustain a high level of synaptic activity for more than a few minutes, and the seizure ends spontaneously. However, the uncontrolled recurrence of seizures is believed to cause further damage to the already injured neurons, and can be potentially harmful to healthy cells.15,36 In particular, seizures can cause structural and functional changes in neuronal pathways, resulting in impaired cerebral activity and increased susceptibility to additional seizures.22,36... 

Proctolin appears to potentiate synaptic transmission in the central nervous system of the cockroach P. americana (37). Bursts of spike activity in the ventral nerve cord of this insect were elicited by mechanical stimulation of the cereal organs. In the presence of micromolar proctolin, the peak frequency and the duration of bursts were slowly, but significantly, increased. Carbacol, by comparison, caused an immediate enhancement of spontaneous activity, but potentiation of bursts was not observed. Thus, it was concluded that proctolin might function as a neuromodulator in the terminal ganglion. 

The only published study on presynaptlc effects of the more potent ChE inhibitors is that of Abraham and Edery (49), who examined the effect of soman on synaptic transmission in rat diaphragm. In vitro, soman increased the frequency of MEPPs (an effect blocked by Mg ), caused muscle depolarization that reversed spontaneously, and Increased quantal content. It was suggested that the observed changes in transmitter release resulted from an effect on the action potential invading the nerve terminal, although no direct evidence was offered. 

Glaucine was found to affect synaptic transmission in a fairly complicated manner. The alkaloid reduced the amplitude of spontaneous miniature end plate potentials in the frog neuromuscular junction. At low concentrations, glaucine diminished the frequency of miniature potentials, but increased it when the concentration exceeded a certain value. Glaucine provokes muscle contracture if present at a relatively high concentration [250]. 

Thymoquinone. Thymoquinone (TQ) is the main constituent of the oil extracted from Nigella sativa seeds, with antioxidant and anti-inflammatory effects. Treatment with TQ efficiently attenuates APi 2-induced neurotoxicity, inhibits the mitochondrial membrane potential depolarization and ROS generation caused by Api 2, restores synaptic vesicle recycling inhibition, partially reverses the loss of spontaneous firing activity, and inhibits A(f aggregation in vitro [291],... 

In the first full report to evaluate the direct effects of ketones on neurons. Thio and colleagues examined the effects of direct ketone application on excitatory and inhibitory synaptic transmission in hippocampus slices or cultures (Thio et al., 2000). They found no effect of either p-OHB or AcAc on any aspect of synaptic function tested, including GABA- and NMDA-evoked inhibitory or excitatory currents, respectively (Fig. 2) CAl field excitatory postsynaptic potentials or spontaneous epileptiform discharges elicited by 4-aminopyridine. They concluded that ketones do not directly alter membrane excitability, as neither excitation nor inhibition was altered. Clearly, additional studies into ketone modulation of cortical excitability are urgently needed. 

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