Recruitment of neurons into neural ensembles based on dendritic plateau potentials

Prefrontal cortex plays a crucial role in advanced cognitive functions. Previous experimental observation has shown that glutamatergic inputs to the basal dendrites of cortical pyramidal neurons activate AMPA and NMDA receptors which can bring the dendrites into a long-lasting depolarized state: a dendritic plateau potential. These sustained depolarizations push the cell body towards spike threshold and reduce the membrane time constant. In such a ``Prepared'' state, the pyramidal cells can respond to other sparse synaptic inputs more quickly and easily, facilitating synchronization of firing. During the plateau depolarization, a neuron can tune into ongoing network activity and synchronize spiking with other neurons to provide a coordinated ``Active'' state (robust firing of somatic action potentials), which would permit ``binding'' of signals through coordination of neural activity across a population. Under this scenario, Active cells are recruited from cells in the Prepared state, and therefore the transient Active ensemble is embedded in the longer-lasting Prepared ensemble of neurons. We hypothesize that ``embedded ensemble encoding'' may be an important organizing principle in networks of neurons, explaining how electrical signaling endows central nervous system with capacity to form large number of neural ensembles. Also, embedded ensemble encoding pulls together two concepts (rate coding vs. temporal coding) that are typically seen to be in opposition. We have developed a morphologically-detailed model reconstructed from a cortical Layer 5 prefrontal pyramidal neuron in the NEURON simulator. Both synaptic AMPA/NMDA and extrasynaptic NMDA inputs are placed on basal dendrites to model the induction of plateau potentials (Fig. 1a–d). The active properties of the cell are tuned to match the amplitude and duration of experimentally observed plateau potentials utilizing voltage-sensitive dyes in dendrites and whole-cell patch recording in soma (Fig. 1e). In addition, the effects of input location, receptor conductance, calcium-activated potassium channels and voltage-activated calcium channels are explored in detail. These findings help us to better understand the implications of dendritic plateaus at the cellular and network level. In the future, this detailed individual cell model can be used to develop cortical meso-scale network models for exploring the hypotheses pertaining to the recruitment of neurons into neural ensembles.Fig. 1Modeling of the glutamate evoked dendritic plateau potentials