Dendritic Nonlinearities Reduce Network Size Requirements and Mediate ON and OFF States of Persistent Activity in a PFC Microcircuit Model

Abstract

Technological advances have unraveled the existence of small clusters of co-active neurons in the neocortex. The functional implications of these microcircuits are in large part unexplored. Using a heavily constrained biophysical model of a L5 PFC microcircuit, we recently showed that these structures act as tunable modules of persistent activity, the cellular correlate of working memory. Here, we investigate the mechanisms that underlie persistent activity emergence (ON) and termination (OFF) and search for the minimum network size required for expressing these states within physiological regimes. We show that (a) NMDA-mediated dendritic spikes gate the induction of persistent firing in the microcircuit. (b) The minimum network size required for persistent activity induction is inversely proportional to the synaptic drive of each excitatory neuron. (c) Relaxation of connectivity and synaptic delay constraints eliminates the gating effect of NMDA spikes, albeit at a cost of much larger networks. (d) Persistent activity termination by increased inhibition depends on the strength of the synaptic input and is negatively modulated by dADP. (e) Slow synaptic mechanisms and network activity contain predictive information regarding the ability of a given stimulus to turn ON and/or OFF persistent firing in the microcircuit model. Overall, this study zooms out from dendrites to cell assemblies and suggests a tight interaction between dendritic non-linearities and network properties (size/connectivity) that may facilitate the short-memory function of the PFC.

Contribution of Apical and Basal Dendrites of L2/3 Pyramidal Neurons to Orientation Encoding in Mouse V1

“…Moreover, apical dendrite ablation eliminates the contribution of regenerative potentials on distal dendrites 30 , which have been observed during complex behavioral task in vivo 31 or L1 stimulation in vitro 32 . Our results suggest that neurons can still compute orientation tuning without those regenerative dendritic electrical events, favoring a feedforward model for orientation selectivity 33,34 . Computational modeling confirmed that basal dendritic input is dominant over a wide range of synaptic input parameters.…”

Calcium regulation of HCN channels supports persistent activity in a multiscale model of neocortex

“…In the current study, we see how a persistent activity attractor landscape can be formed by complementing the effects of mutual excitation with the multiple complementary effects of excitatory and inhibitory interactions across cortical layers (Papoutsi et al, 2013, Papoutsi et al, 2014, Nelson et al, 2003, Marder et al, 1996). By contrast, Wang’s “bump attractor” network model was based on localized connectivity in a single layer of integrate-and-fire neurons (Compte et al, 2000, Wang, 2001).…”

Structured connectivity exploits NMDA non-linearities to enable flexible encoding of multiple memoranda in a PFC circuit model

“…Dependent on the spatial arrangement of incoming inputs, the nonlinear integration properties of NMDARs can rapidly shift synaptic efficacies and enable the network to differentially integrate information for short periods of time (Buzsáki, 2010; Stokes, 2015). This is based on several lines of evidence indicating that NMDA receptors are important for PFC function (Lisman et al, 1998; Papoutsi et al, 2014; Wang, 1999; Wang et al, 2013). Furthermore, maximal exploitation of NMDA non-linearities is achieved by connecting subsets of neurons in a clustered, hyper-reciprocal manner, as evidenced in the PFC anatomy (Wang et al, 2006), and previously hypothesized to be beneficial for memory (Brunel, 2016).…”

“…adaptive coding (Stokes et al, 2013). In support of this hypothesis, NMDA-dependent dendritic non-linearities have been shown to underlie the expression of memory states in computational models of small cell assemblies (Papoutsi et al, 2014, 2017).…”