Finally, the strength of a dendritic spike on a particular dendritic branch has been shown to undergo activity- and experience-dependent plasticity (Losonczy et al., 2008; Makara et al., 2009). However, the functional interaction of dendritic NA+ spikes and inhibitory GABAergic microcircuits is so far completely unknown. Therefore, it is important to resolve how dendritic spikes could maintain their specific signaling functions, while interacting with an activity-dependent inhibitory micronetwork. The central question of this study is how linear and nonlinear excitatory signals in CA1 dendrites are controlled by recurrent inhibition. We coactivated excitation and inhibition by simultaneously

Selleck Selisistat using branch-targeted microiontophoresis of glutamate together with either selective electrical stimulation of CA1 recurrent inhibitory microcircuits or local GABA microiontophoresis. We demonstrate that correlated excitatory input on highly excitable dendritic branches can resist recurrent inhibitory control by initiating strong dendritic spikes, whereas inputs on other branches are subjected to powerful and dynamic regulation by inhibition. Selleckchem Ivacaftor Moreover, potentiation of branch excitability serves to achieve effective coupling of branch input to precisely triggered action potential output, independent of recurrent inhibition. To examine the interaction of dendritic excitation and inhibition

it is necessary to evoke spatially defined excitation. We achieved this tuclazepam by using glutamate microiontophoresis locally on dendritic branches of CA1 pyramidal neurons (Figure 1A;

Figures S2A and S2B available online; see also Experimental Procedures). Systematically increasing the iontophoretic current caused somatic EPSPs (iEPSPs) of increasing amplitude, which ultimately triggered action potentials (Figure 1B). The iEPSPs initially increased linearly in all branches, but a subset of basal and apical oblique dendrites exhibited supralinear dendritic spikes (Figure 1C). Supralinear events were not observed when microiontophoretic stimulation was applied to apical tuft dendrites (n = 42 branches; Figure S3). In the somatic recording, the dendritic spike manifested as a fast spikelet riding on the iEPSP followed by a slower NMDA receptor and voltage gated Ca2+ channel dependent component (Losonczy and Magee, 2006). The fast spikelet could be easily detected as a sudden increase of the first derivative of the voltage signal (ΔV/Δt; Figure 1C, lower traces). The latencies of the fast spikelet components did not differ significantly between weak (median latency 4.5 ± 2.6 ms SD; n = 186 dendritic spikes) and strong dendritic spikes (median latency 3.9 ± 2.2 ms SD, n = 185 dendritic spikes; p > 0.05; Mann-Whitney test, data not shown); yet, weak dendritic spikes showed higher temporal jitter (F-test, data not shown).