Serotonin Modulates Spike Backpropagation and Associated [Ca²⁺]_iChanges in the Apical Dendrites of Hippocampal CA1 Pyramidal Neurons

Abstract

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.

Associative Long-Term Depression in the Hippocampus Is Dependent on Postsynaptic N-Type Ca2+Channels

“…Application of 1 M OH-DPAT reduced the dendritic Ca 2ϩ transients by 25.6 Ϯ 2.7% (n ϭ 5; 40 -100 m). This is consistent with the previously reported reduction of burst-induced Ca 2ϩ transients by 10 M 5-HT in CA1 pyramidal neurons (Sandler and Ross, 1999).…”

“…For 10 M 5-HT a slight reduction of the amplitude of the backpropagating action potentials was reported (Sandler and Ross, 1999). To distinguish between these possibilities, we blocked Na ϩ and K ϩ channels (see Materials and Methods) and examined Ca 2ϩ channels in isolation in the whole-cell voltage-clamp configuration using 2 mM Ba 2ϩ as charge carrier (Fig.…”

“…A 1 M concentration of OH-DPAT, which is thought to activate selectively 5-HT 1A receptors, did not affect the properties of the backpropagated spike within the first 200 m of the apical dendrite. In contrast, higher concentrations (30 M) of OH-DPAT and 5-HT induce a marked hyperpolarization of CA1 pyramidal cells by 5 and 14 mV, respectively (Andrade and Nicoll, 1987), which slightly decrease the amplitude of the backpropagated spike (Sandler and Ross, 1999). Furthermore, activation of muscarinic and adrenergic receptors regulates dendritic excitability via modulation of fast dendritic Na ϩ and K ϩ channels (Johnston et al, 1999).…”

The Role of Dendritic Filtering in Associative Long-Term Synaptic Plasticity

“…Serotonin acts through a different mechanism as it hyperpolarizes both the soma and apical dendrites (Sandler and Ross 1999). In this study, it was shown that serotonin has varying effects on back-propagating APs, depending on the neuronal compartment.…”

Measurement of Intracellular Calcium

“…The properties of bis-fura 2 that distinguish it from fura 2 are the following: 1) the emitted fluorescence intensity is about twice that of fura 2, which allows reduction of dye concentration; 2) the K d is larger than that of fura 2, which expands the measurable [Ca 2ϩ ] range especially in the range above 500 nM of Ca 2ϩ ; and 3) it has more negative charges, which facilitate better dye retention within the cytosol. One of disadvantages of bis-fura 2 is that it has been provided commercially only as a cellimpermeable form that requires invasive loading methods (337).…”