Frontiers in Systems Neuroscience (Mar 2014)
Interplay of dendritic non-linearities and network size mediate persistent activity in a PFC microcircuit model
Abstract
The ways in which neurons are embedded in a network to support various computations determines the functional output of the cortex. Recently, a number of in vivo studies have shown that dendritic integration in pyramidal neurons shapes neuronal function (Smith et al., 2013; Longordo et al., 2013) and that clusters of few reciprocally connected neurons are co-activated during behavioral tasks (Ko et al., 2011, 2013; Morishima et al., 2011). In the prefrontal cortex (PFC), such microcircuits are linked to persistent activity (prolonged spiking activity that exceeds stimulus presentation), which is the cellular correlate of working memory (Papoutsi et al., 2013). However, the effect of dendritic integration on the functional output of such small microcircuits has remained unexplored. In this work, we investigate the contribution of nonlinear dendritic properties to the induction and coding of upcoming state transitions in PFC microcircuits. Towards this goal we used a heavily constrained biophysical model of a layer 5 PFC microcircuit consisting of 7 pyramidal neurons and 2 interneurons implemented in the NEURON simulation environment. All neuron models are biophysically detailed but morphologically simplified and validated regarding their intrinsic, synaptic and connectivity properties (Papoutsi et al., 2013). Our results show that the non-linear integration of synaptic inputs at the basal dendrites of pyramidal neurons, mediated by the induction of NMDA spikes, is imperative for the emergence of the persistent state in the microcircuit: if synaptic drive is sufficient to induce NMDA spikes, the minimum network size required for persistent activity induction can be reduced down to 2 cells. In addition, slow synaptic mechanisms, such as the NMDA and GABAB currents, determine the ability of a given stimulus to induce persistent firing in the microcircuit model. On the other hand, the necessity for NMDA spikes disappears when persistent activity depends on larger scale networks (of the order of hundreds of neurons) with relaxed conductivity delays. Overall, this study zooms out from dendrites to cell assemblies and suggests that there is a tradeoff between dendritic non-linearities and network properties (size/connectivity) in mediating the short-memory function of the PFC.
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