Synaptic noise improves detection of subthreshold signals in hippocampal CA1 neurons.

Stochastic resonance (SR) is a phenomenon whereby the detection of a low-level signal is enhanced in a nonlinear system by the introduction of noise. Studies of the effects of SR in neurons have suggested that noise could play a prominent role in improving detection of small signals. Most experimental SR research has focused on the role of noise in sensory neurons using physiological stimuli. Computer simulations show that signal detection in hippocampal neurons is improved by the addition of physiological levels of noise applied extracellularly to synaptic inputs. These results were confirmed experimentally. We now report that endogenous noise sources can also improve signal detection. The noise source was generated by modulating the random synaptic activity on the apical dendrites of CA1 cells in rat hippocampal slices using subthreshold cathodic current. Intracellular recordings of CA1 cells showed that even small increases of synaptic noise are able to greatly improve the detection of an independent, synaptic, subthreshold stimulus as predicted by the simulations. The noise variance in the CA1 cell was compared with the resting variance and with variance changes caused by several endogenous noise sources. In all cases, the increased noise variance was well within the physiological range. These results were supplemented and analyzed with a CA1 computer model. The improved signal detection with small amounts of endogenous noise suggests that the diverse inputs to CA1 are able to improve detection of subthreshold synaptic signals and could provide a means to modulate detection of specific inputs in the hippocampus.

Suppression of epileptiform activity by high frequency sinusoidal fields in rat hippocampal slices.

1. Sinusoidal high frequency (20-50 Hz) electric fields induced across rat hippocampal slices were found to suppress zero-Ca2+, low-Ca2+, picrotoxin, and high-K+ epileptiform activity for the duration of the stimulus and for up to several minutes following the stimulus. 2. Suppression of spontaneous activity by high frequency stimulation was found to be frequency (< 500 Hz) but not orientation or waveform dependent. 3. Potassium-sensitive microelectrodes showed that block of epileptiform activity was always coincident with a stimulus-induced rise in extracellular potassium concentration during stimulation. Post-stimulus inhibition was always associated with a decrease in extracellular potassium activity below baseline levels. 4. Intracellular recordings and optical imaging with voltage-sensitive dyes showed that during suppression neurons were depolarized yet did not fire action potentials. 5. Direct injection of sinusoidal current into individual pyramidal cells did not result in a tonic depolarization. Injection of large direct current (DC) depolarized neurons and suppressed action potential generation. 6. These findings suggest that high frequency stimulation suppresses epileptiform activity by inducing potassium efflux and depolarization block.

Stochastic resonance improves signal detection in hippocampal CA1 neurons.

Stochastic resonance (SR) is a phenomenon observed in nonlinear systems whereby the introduction of noise enhances the detection of a subthreshold signal for a certain range of noise intensity. The nonlinear threshold detection mechanism that neurons employ and the noisy environment in which they reside makes it likely that SR plays a role in neural signal detection. Although the role of SR in sensory neural systems has been studied extensively, its role in central neurons is unknown. In many central neurons, such as the hippocampal CA1 cell, very large dendritic trees are responsible for detecting neural input in a noisy environment. Attenuation due to the electrotonic length of these trees is significant, suggesting that a method other than passive summation is necessary if signals at the distal ends of the tree are to be detected. The hypothesis that SR plays an important role in the detection of distal synaptic inputs first was tested in a computer simulation of a CA1 cell and then verified with in vitro rat hippocampal slices. The results clearly showed that SR can enhance signal detection in CA1 hippocampal cells. Moreover, high levels of noise were found to equalize detection of synaptic signals received at varying positions on the dendritic tree. The amount of noise needed to evoke the effect is compared with physiological noise in slices and in vivo.

Surface charge and lanthanum block of calcium current in bullfrog sympathetic neurons.

The density of surface charge associated with the calcium channel pore was estimated from the effect of extracellular ionic strength on block by La3+. Currents carried by 2 mM Ba2+ were recorded from isolated frog sympathetic neurons by the whole-cell patch-clamp technique. In normal ionic strength (120 mM N-methyl-D-glucamine, NMG), La3+ blocked the current with high affinity (IC50 = 22 nM at 0 mV). La3+ block was relieved by strong depolarization in a time- and voltage-dependent manner. After unblocking, open channels reblocked rapidly at 0 mV, allowing estimation of association and dissociation rates for La3+: k(on) = (7.2 +/- 0.7) x 10(8) M(-1) s(-1), k(off) = 10.0 +/- 0.5 s(-1). To assess surface charge effects, La3+ block was also measured in low ionic strength (12.5 mM NMG) and high ionic strength (250 mM NMG). La3+ block was higher affinity and faster by two- to threefold in 12.5 mM NMG, with little effect of 250 mM NMG. The data could be described by Gouy-Chapman theory with a surface charge density of approximately 1 e-/3000-4000 A2. These results indicate that there is a small but detectable surface charge associated with the pore of voltage-dependent calcium channels.