Inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release evoked by metabotropic agonists and backpropagating action potentials in hippocampal CA1 pyramidal neurons.

We examined the properties of [Ca(2+)](i) changes that were evoked by backpropagating action potentials in pyramidal neurons in hippocampal slices from the rat. In the presence of the metabotropic glutamate receptor (mGluR) agonists t-ACPD, DHPG, or CHPG, spikes caused Ca(2+) waves that initiated in the proximal apical dendrites and spread over this region and in the soma. Consistent with previously described synaptic responses (Nakamura et al., 1999a), pharmacological experiments established that the waves were attributable to Ca(2+) release from internal stores mediated by the synergistic effect of receptor-mobilized inositol 1,4, 5-trisphosphate (IP(3)) and spike-evoked Ca(2+). The amplitude of the changes reached several micromoles per liter when detected with the low-affinity indicators fura-6F, fura-2-FF, or furaptra. Repetitive brief spike trains at 30-60 sec intervals generated increases of constant amplitude. However, trains at intervals of 10-20 sec evoked smaller increases, suggesting that the stores take 20-30 sec to refill. Release evoked by mGluR agonists was blocked by MCPG, AIDA, 4-CPG, MPEP, and LY367385, a profile consistent with the primacy of group I receptors. At threshold agonist concentrations the release was evoked only in the dendrites; threshold antagonist concentrations were effective only in the soma. Carbachol and 5-HT evoked release with the same spatial distribution as t-ACPD, suggesting that the distribution of neurotransmitter receptors was not responsible for the restricted range of regenerative release. Intracellular BAPTA and EGTA were approximately equally effective in blocking release. Extracellular Cd(2+) blocked release, but no single selective Ca(2+) channel blocker prevented release. These results suggest that IP(3) receptors are not associated closely with specific Ca(2+) channels and are not close to each other.

Calcium-induced calcium release contributes to action potential-evoked calcium transients in hippocampal CA1 pyramidal neurons.

Calcium-induced calcium release (CICR) is a mechanism by which local elevations of intracellular calcium (Ca2+) are amplified by Ca2+ release from ryanodine-sensitive Ca2+ stores. CICR is known to be coupled to Ca2+ entry in skeletal muscle, cardiac muscle, and peripheral neurons, but no evidence suggests that such coupling occurs in central neurons during the firing of action potentials. Using fast Ca2+ imaging in CA1 neurons from hippocampal slices, we found evidence for CICR during action potential-evoked Ca2+ transients. A low concentration of caffeine enhanced Ca2+ transient amplitude, whereas a higher concentration reduced it. Simultaneous Ca2+ imaging and whole-cell recordings showed that membrane potential, action potential amplitude, and waveform were unchanged during caffeine application. The enhancement of Ca2+ transients by caffeine was not affected by the L-type channel blocker nifedipine, the phosphodiesterase inhibitor IBMX, the adenylyl cyclase activator forskolin, or the PKA antagonist H-89. However, thapsigargin or ryanodine, which both empty intracellular Ca2+ stores, occluded this effect. In addition, thapsigargin, ryanodine, and cyclopiazonic acid reduced action potential-evoked Ca2+ transients in the absence of caffeine. These results suggest that Ca2+ release from ryanodine-sensitive stores contributes to Ca2+ signals triggered by action potentials in CA1 neurons.

Serotonin modulates spike backpropagation and associated [Ca2+]i changes in the apical dendrites of hippocampal CA1 pyramidal neurons.

The effect of serotonin (5-HT) on somatic and dendritic properties was analyzed in pyramidal neurons from the CA1 region in slices from the rat hippocampus. Bath-applied 5-HT (10 microM) hyperpolarized the soma and apical dendrites and caused a conductance increase at both locations. In the dendrites (200-300 microm from the soma) trains of antidromically activated, backpropagating action potentials had lower peak potentials in 5-HT than in normal artificial cerebrospinal fluid. Spike amplitudes were about the same in the two solutions. Similar results were found when the action potentials were evoked synaptically with stimulation in the stratum oriens. In the soma, spike amplitudes increased in 5-HT, with only a small decrease in the peak potential. Calcium concentration measurements, made with bis-fura-2 injected through patch electrodes, showed that the amplitude of the [Ca2+]i changes was reduced at all locations in 5-HT. The reduction of the [Ca2+]i change in the soma was confirmed in slices where cells were loaded with fura-2-AM. The reduction at the soma in 5-HT, where the spike amplitude increased, suggests that the reduction is due primarily to direct modulation of Ca2+ channels. In the dendrites, the reduction is due to a combination of this channel modulation and the lowering of the peak potential of the action potentials.

Intrinsic response properties of bursting neurons in the nucleus principalis trigemini of the gerbil.

In trigeminal neurons, the spike rate, modulated by input parameters, may serve as a code for sensory information. We investigated intrinsic response properties that affect rate coding in neurons of nucleus principalis trigemini (young gerbils). Using the whole-cell recording technique and neurobiotin staining in slices, we found bursting behaviour in approximately 50% of the neurons. These neurons fired spike bursts, spontaneously, as well as at the onset of depolarizing, and offset of hyperpolarizing, current pulses. The spike rate within an initial burst was independent of stimulus strength, in contrast to single spike firing that occurred later in the response to current pulse injection. The spikes within a burst were superimposed on slow depolarizing humps. Under favourable conditions, these led to "plateau potentials", that lasted for hundreds of milliseconds at membrane potentials near approximately -20 mV. Occasionally, plateau potentials were spontaneous or evoked under control conditions: usually, they were evoked by current pulse injection during blockade of Ca2+ influx with Co2+ or Cd2+ in Ca(2+)-free extracellular media, or during blockade of K+ currents with tetraethylammonium. The plateau potentials recorded during internal Cs+ (132.5 mM) substitution of K+ had more positive amplitudes (near +20 mV). Despite relatively stable depolarization levels, the plateau potentials decreased in duration and decayed in amplitude during application of tetrodotoxin (0.6-1.8 nM). Higher tetrodotoxin concentrations (5-60 nM) eliminated the plateau potentials despite well-maintained, fast action potentials. A reduction of external [Na+] reduced the amplitudes of the spikes and plateau potentials. A hyperpolarization of long duration (> 3 s) followed a plateau potential, or a depolarizing response that was subthreshold for plateau generation. Tetrodotoxin application blocked this after-effect. We suggest that a persistent Na+ influx is a major contributor to the bursts and plateau potentials and that it mediates the hyperpolarization. Depending on Ca2+ influx, K+ conductances may regulate the amplitudes of these long-lasting depolarizations. A Ca2+ conductance, blockable by Ni2+, may support burst initiation in these neurons. In very young animals (P2-P9), we found only non-bursting neurons. Both bursting and non-bursting neurons with elongated dendritic fields showed inward rectification on hyperpolarization. The bursts in nucleus principalis trigemini neurons emphasize the onsets of stimulus transients, at the expense of using firing rate as a sensory code. Our studies describe neurons with a surprising ability to distort sensory signals, transforming depolarizing inputs into bursts of spikes by virtue of a Na(+)-conductance activation. The principal trigeminal nucleus also contains neurons with tonic firing ability, compatible with simple rate coding.

A model for detection of spatial and temporal edges by a single X cell.

When an inhibitory visual stimulus is turned off, an increased rate of spike discharge is evoked which we term the "rebound response". This response exists as a part of different cell responses from the retina to the cortex. The rebound response, with its temporal dependence on stimulus parameters, has not been previously considered in models. Here we present such a model, and also show its dependence on stimulus duration and its turning off rate. The rebound response enables detection of temporal changes when a visual stimulus involves spatial changes. The temporal change detection is affected by the actual stimulus duration, which can also be seen as a cell memory operation.