Basal dendrites are a major target for synaptic inputs innervating cortical pyramidal neurons. At present little is known about signal processing in these fine dendrites. Here we show that coactivation of clustered neighbouring basal inputs initiated local dendritic spikes, which resulted in a 5.9 +/- 1.5 mV (peak) and 64.4 +/- 19.8 ms (half-width) cable-filtered voltage change at the soma that amplified the somatic voltage response by 226 +/- 46%. These spikes were accompanied by large calcium transients restricted to the activated dendritic segment. In contrast to conventional sodium or calcium spikes, these spikes were mediated mostly by NMDA (N-methyl-D-aspartate) receptor channels, which contributed at least 80% of the total charge. The ionic mechanism of these NMDA spikes may allow 'dynamic spike-initiation zones', set by the spatial distribution of glutamate pre-bound to NMDA receptors, which in turn would depend on recent and ongoing activity in the cortical network. In addition, NMDA spikes may serve as a powerful mechanism for modification of the cortical network by inducing long-term strengthening of co-activated neighbouring inputs.

We compared the transient increase of Ca

1. Calcium dynamics associated with a single action potential (AP) were studied in single boutons of the axonal arbor of layer 2Ï3 pyramidal cells in the neocortex of young (P14-16) rats. We used fluorescence imaging with two-photon excitation and Ca¥-selective fluorescence indicators to measure volume-averaged Ca¥ signals. These rapidly reached a peak (in about 1 ms) and then decayed more slowly (tens to hundreds of milliseconds). 2. Single APs and trains of APs reliably evoked Ca¥ transients in en passant boutons located on axon collaterals in cortical layers 2Ï3, 4 and 5, indicating that APs propagate actively and reliably throughout the axonal arbor. Branch point failures are unlikely to contribute to differences in synaptic efficacy and reliability in the connections made by layer 2Ï3 pyramidal cells. 3. AP-evoked Ca¥ transients in boutons were mediated by voltage-dependent Ca¥ channels (VDCCs), predominantly by the PÏQ-and N-subtypes. 4. Ca¥ transients were, on average, of significantly larger amplitude in boutons than in the flanking segments of the axon collateral. Large amplitude Ca¥ transients in boutons were spatially restricted to within û 3 ìm of axonal length. 5. Single AP-evoked Ca¥ transients varied up to 10-fold across different boutons even if they were located on the same axon collateral. In contrast, variation of Ca¥ transients evoked by successive APs in a given single bouton was small (coefficient of variation, c.v. û 0·21). 6. Amplitudes of AP-evoked Ca¥ signals did not correlate with the distance of boutons from the soma. In contrast, AP-evoked Ca¥ signals in spines of basal dendrites decreased slightly (correlation coefficient, r 2 = −0·27) with distance from the soma. Keywords:

The efficacy and short-term modification of neocortical synaptic connections vary with the type of target neuron. We investigated presynaptic Ca2+ and release probability at single synaptic contacts between pairs of neurons in layer 2/3 of the rat neocortex. The amplitude of Ca2+ signals in boutons of pyramids contacting bitufted or multipolar interneurons or other pyramids was dependent on the target cell type. Optical quantal analysis at single synaptic contacts suggested that release probabilities are also target cell-specific. Both the Ca2+ signal and the release probability of different boutons of a pyramid contacting the same target cell varied little. We propose that the mechanisms that regulate the functional properties of boutons of a pyramid normalize the presynaptic Ca2+ influx and release probability for all those boutons that innervate the same target cell.