title: Effects of Neural Morphology and Input Distribution on Synaptic Processing by Global and Focal NMDA-Spikes.
abstract: Cortical neurons can respond to glutamatergic stimulation with regenerative N-Methyl-D-aspartic acid (NMDA)-spikes. NMDA-spikes were initially thought to depend on clustered synaptic activation. Recent work had shown however a new variety of a global NMDA-spike, which can be generated by randomly distributed inputs. Very little is known about the factors that influence the generation of these global NMDA-spikes, as well the potentially distinct rules of synaptic integration and the computational significance conferred by the two types of NMDA-spikes. Here I show that the input resistance (RIN) plays a major role in influencing spike initiation; while the classical, focal NMDA-spike depended upon the local (dendritic) RIN, the threshold of global NMDA-spike generation was set by the somatic RIN. As cellular morphology can exert a large influence on RIN, morphologically distinct neuron types can have dissimilar rules for NMDA-spikes generation. For example, cortical neurons in superficial layers were found to be generally prone to global NMDA-spike generation. In contrast, electric properties of cortical layer 5b cells clearly favor focal NMDA-spikes. These differences can translate into diverse synaptic integration rules for the different classes of cortical cells; simulated superficial layers neurons were found to exhibit strong synaptic interactions between different dendritic branches, giving rise to a single integrative compartment mediated by the global NMDA-spike. In these cells, efficiency of postsynaptic activation was relatively little dependent on synaptic distribution. By contrast, layer 5b neurons were capable of true multi-unit computation involving independent integrative compartments formed by clustered synaptic input which could trigger focal NMDA-spikes. In a sharp contrast to superficial layers neurons, randomly distributed synaptic inputs were not very effective in driving firing the layer 5b cells, indicating a possibility for different computation performed by these important cortical neurons.
authors.affiliation: Synaptic Physiology Section, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Alon
authors.initials: A
authors.lastname: Poleg-Polsky
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism; D062211:Spatio-Temporal Analysis; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D015221:Potassium Channels; D016202:N-Methylaspartate