Dendritic Spikes Are Enhanced by Cooperative Network Activity in the Intact Hippocampus

Abstract

In vitro experiments suggest that dendritic fast action potentials may influence the efficacy of concurrently active synapses by enhancing Ca2+ influx into the dendrites. However, the exact circumstances leading to these effects in the intact brain are not known. We have addressed these issues by performing intracellular sharp electrode recordings from morphologically identified sites in the apical dendrites of CA1 pyramidal neurons in vivo while simultaneously monitoring extracellular population activity. The amplitude of spontaneous fast action potentials in dendrites decreased as a function of distance from the soma, suggesting that dendritic propagation of fast action potentials is strongly attenuated in vivo. Whereas the amplitude variability of somatic action potentials was very small, the amplitude of fast spikes varied substantially in distal dendrites. Large-amplitude fast spikes in dendrites occurred during population discharges of CA3-CA1 neurons concurrent with field sharp waves. The large-amplitude fast spikes were associated with bursts of smaller-amplitude action potentials and putative Ca2+ spikes. Both current pulse-evoked and spontaneously occurring Ca2+ spikes were always preceded by large-amplitude fast spikes. More spikes were observed in the dendrites during sharp waves than in the soma, suggesting that local dendritic spikes may be generated during this behaviorally relevant population pattern. Because not all dendritic spikes produce somatic action potentials, they may be functionally distinct from action potentials that signal via the axon.

The Properties and Implications of NMDA Spikes in Neocortical Pyramidal Cells

“…In the simulation, this question was first addressed by application of an inhibitory conductance with GABA A -type kinetics colocalized with focal excitatory input. The results revealed extremely sensitive control of NMDA events by colocalized inhibition, reminiscent of that reported for the control of dendritic Ca 2ϩ spikes in vitro (Miles et al, 1996;Tsubokawa and Ross, 1996;Kamondi et al, 1998). Even when the synaptic conductance driving the NMDA event was much larger, and with substantial densities of depolarizing Na ϩ and Ca 2ϩ currents in the dendritic membrane, a much smaller (in some cases exceeding 20-fold) inhibitory conductance could completely prevent the NMDA spike (Fig.…”

Synaptically Recruited Apical Currents Are Required to Initiate Axonal and Apical Spikes in Hippocampal Pyramidal Cells: Modulation by Inhibition

“…The number of simultaneously active inputs may vary enormously, and the degree of synchronization will decide whether a dendritic spike will be initiated, conducted in a continuous or pseudosaltatory way to the axon or simply backpropagated from there. The necessary degree of excitatory synchronization may be largely surpassed during some physiological electrographic patterns, as hippocampal sharp waves (e.g., Kamondi et al 1998). In any case, beyond the role of dendritic spikes, these results underscore the importance of subthreshold envelope-like currents.…”

Extracellular Calcium Modulates Persistent Sodium Current-Dependent Burst-Firing in Hippocampal Pyramidal Neurons

“…There is convincing evidence that the spike bursts (or "complex spikes") are generated intrinsically by slow, voltagegated membrane currents (Kandel and Spencer, 1961;Fujita, 1975;Nuñez et al, 1990;Kamondi et al, 1998). Such bursts are thought to play important roles in electrical signaling, in neuronal synchronization, and in the induction of long-term synaptic plasticity (for review, see Lisman, 1997).…”