Synaptic Integration in Tuft Dendrites of Layer 5 Pyramidal Neurons: A New Unifying Principle

Abstract

Tuft dendrites are the main target for feedback inputs innervating neocortical layer 5 pyramidal neurons, but their properties remain obscure. We report the existence of N-methyl-D-aspartate (NMDA) spikes in the fine distal tuft dendrites that otherwise did not support the initiation of calcium spikes. Both direct measurements and computer simulations showed that NMDA spikes are the dominant mechanism by which distal synaptic input leads to firing of the neuron and provide the substrate for complex parallel processing of top-down input arriving at the tuft. These data lead to a new unifying view of integration in pyramidal neurons in which all fine dendrites, basal and tuft, integrate inputs locally through the recruitment of NMDA receptor channels relative to the fixed apical calcium and axosomatic sodium integration points.

Extracellular matrix inhibits structural and functional plasticity of dendritic spines in the adult visual cortex

“…3a). The short latency of the response (ranging from 4 to 8 ms) from the extracellular stimulus correlates with the timing of the NMDA postsynaptic spike evoked in L5 pyramidal neurons 29 and is consistent with a monosynaptic response. After obtaining a stable baseline, we delivered a y-burst followed by at least 60 min of further recording.…”

“…The apical tuft of L5 pyramidal cells receives a great number of synapses from horizontal connections running in L1 and 2. The activation of a relatively small number of synapses on different branches of the apical tuft is capable of activating an N-methyl-D-aspartate (NMDA) current in the dendrite that successfully propagates to the cell body 29 . Horizontal intracortical connections were stimulated with a 250 mm concentric electrode placed on the cortex surface.…”

On the functions, mechanisms, and malfunctions of intracortical contextual modulation

“…Calcium spikes are less likely if NMDAR channels are blocked, however, so any such contextual amplification would then be reduced or eliminated (e.g. Larkum et al, 2009;Larkum, 2013). Thus, evidence for this mechanism is in harmony with the evidence reviewed above for a major role of NMDARs in contextual modulation.…”

“…Larkum, Zhu, and Sakmann, 1999). The far-reaching implications of such mechanisms are only now becoming clear, however (Larkum et al, 2009;Larkum, 2013;Major, Larkum and Schiller, 2013;Jadi et al, 2014). In vitro studies of rat somatosensory cortex show that, in addition to the somatic sodium spike initiation zone that triggers axonal action potentials, Layer 5 pyramidal cells have an initiation zone at the base of the apical tuft.…”

Synaptic and extrasynaptic traces of long-term memory: the ID molecule theory

“…The interplay between N-methyl-D-aspartate (NMDA) receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and Mg 2+ ions results in responsiveness to spike coincidence and repetition (Larkum et al, 2009;Major et al, 2013;Palmer et al, 2014). Since a large class of surprising events is distinguished by nothing more than spike coincidence and repetition, these receptor systems make for highly effective surprise detectors.…”