There is controversy concerning whether orthodromic action potentials originate from the apical or basal dendrites of CA1 pyramidal cells in vivo. The participation of the dendrites in the initialization and propagation of population spikes in CA1 of urethan-anesthetized rats in vivo was studied using simultaneously recorded field potentials and current source density (CSD) analysis. CSD analysis revealed that the antidromic population spike, evoked by stimulation of the alveus, invaded in succession, the axon initial segment (stratum oriens), cell body and approximately 200 microm of the proximal apical dendrites. Excitation of the basal dendrites of CA1, following stimulation of CA3 stratum oriens, evoked an orthodromic spike that started near the cell body or initial segment and then propagated approximately 200 microm into the proximal apical dendrites. In contrast, the population spike that followed excitation of the apical dendrites of CA1 initiated at the proximal apical dendrites, 50-100 microm distal to the cell body layer, and then propagated centripetally to the cell body and the proximal basal dendrites. A late apical dendritic spike may arise in the mid-apical dendrites (250-300 microm from the cell layer) and propagated distally. The origin or the pattern of propagation of each population spike type was similar for near-threshold to supramaximal stimulus intensities. In summary, population spikes following apical dendritic and basal dendritic excitation in vivo appeared to originate from different locations. Apical dendritic excitation evoked a population spike that initiated in the proximal apical dendrites while basal dendritic excitation evoked a spike that started near the initial segment or cell body. An original finding of this study is the propagation of the population spike from basal to apical dendrites in vivo or vice versa. This backpropagation from one dendritic tree to the other may play an important role in the synaptic plasticity among a network of CA3 to CA1 neurons.

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Spike backpropagation has been proposed to enhance dendritic depolarization and synaptic plasticity. However, relatively little is known about the inhibitory control of spike backpropagation in vivo. In this study, the backpropagation of the antidromic spike into the dendrites of CA1 pyramidal cells was studied by extracellular recording in urethane-anesthetized rats. The population antidromic spike (pAS) in CA1 following stimulation of the alveus was recorded simultaneously with a 16-channel silicon probe and analyzed as current source density (CSD). The pAS current sink was shown to sequentially invade the soma and then the apical and basal dendrites. When the pAS was preceded <400 ms by a conditioning orthodromic CA3 stimulus, the apical and basal dendritic spike sinks were reduced and delayed. Dendritic spike suppression was large after a high-intensity CA3 conditioning stimulus that evoked a population spike, small after a low-intensity CA3 conditioning stimulus, and weak after conditioning by another pAS. The late (150-400 ms latency) inhibition of the backpropagating pAS at the apical and basal dendrites was partially relieved by a GABA(B) receptor antagonist, CGP35348 or CGP56999A, given intracerebroventricularly (icv). CGP35348 icv also decreased the latency of the antidromic spike sinks at all depths. A compartment cable model of a CA1 pyramidal cell with excitable dendrites, combined with a model of extracellular potential generation, confirms that GABA(B) receptor activation delays a backpropagating spike and blocks distal dendritic spikes. GABA(B) receptor-mediated conductance increase and hyperpolarization, amplified by removing dendritic I(A) inactivation, contribute to conditioned dendritic spike suppression. In addition, the model shows that slow Na(+) channel inactivation also participates in conditioned spike suppression, which may partly explain the small dendritic spike suppression after conditioning with a weak orthodromic stimulus or another antidromic spike. Thus, both theory and experiment confirm an important role of the GABA(B) receptors in controlling dendritic spike backpropagation.

We hypothesize that endogenous cholinergic modulation of dendritic processing of hippocampal CA1 is layer specific, and it specifically enhances spike output resulting from basal as compared with the apical dendritic excitation. Laminar profiles of evoked field potentials were recorded in the CA1 area of urethane-anesthetized rats using multichannel silicon probes and analyzed as current source density. High-frequency stimulation of the pontis oralis (PnO) attenuated the midapical more than the basal or distal apical dendritic excitatory sink. Population spike (PS) and excitatory sink-PS potentiation resulting from basal dendritic excitation were facilitated, while the PS evoked by apical dendritic stimulation was attenuated by PnO stimulation. Perfusion of cholinergic agonist carbachol onto hippocampal slices in vitro also attenuated the apical more than the basal dendritic excitatory postsynaptic potentials. Excitatory sink attenuation and PS changes after PnO stimulation were blocked by systemic or local scopolamine and by intracerebroventricular (icv) M1 receptor antagonist pirenzepine but not by icv M2 receptor antagonist AFDX-116 or nicotinic antagonists. However, a hippocampal theta rhythm activated by PnO stimulation was blocked by systemic but not by local scopolamine. We conclude that endogenous acetylcholine mediates a stronger presynaptic inhibition of the midapical than basal and distal apical excitation mainly through M1 receptors.