Management of synchronized network activity by highly active neurons

Abstract

Increasing evidence supports the idea that spontaneous brain activity may have an important functional role. Cultured neuronal networks provide a suitable model system to search for the mechanisms by which neuronal spontaneous activity is maintained and regulated. This activity is marked by synchronized bursting events (SBEs)--short time windows (hundreds of milliseconds) of rapid neuronal firing separated by long quiescent periods (seconds). However, there exists a special subset of rapidly firing neurons whose activity also persists between SBEs. It has been proposed that these highly active (HA) neurons play an important role in the management (i.e. establishment, maintenance and regulation) of the synchronized network activity. Here, we studied the dynamical properties and the functional role of HA neurons in homogeneous and engineered networks, during early network development, upon recovery from chemical inhibition and in response to electrical stimulations. We found that their sequences of inter-spike intervals (ISI) exhibit long time correlations and a unimodal distribution. During the network's development and under intense inhibition, the observed activity follows a transition period during which mostly HA neurons are active. Studying networks with engineered geometry, we found that HA neurons are precursors (the first to fire) of the spontaneous SBEs and are more responsive to electrical stimulations.

Spontaneous Activity Characteristics of 3D “Optonets”

“…(1) Both culture types present early onset of sporadic activity [dominant up to day 7 in 2D cortical cultures, (Hinard et al, 2012) vs. day 8 in our data], and subsequently of synchronous activity bursts (day ≤ 6 for optonets vs. day 4 for 2D cultures Shein et al, 2008). (2) The rate of these periodic synchronized bursts peaked during days 17–23 vs. day 21 in 2D cultures (Kamioka et al, 1996).…”

“…This process is accompanied by spontaneous neuronal activity (Feller, 1999; Blankenship and Feller, 2010), which further stimulate neural connectivity and axonal branching (Katz and Shatz, 1996; Ruthazer and Cline, 2004; Uesaka et al, 2006). Spontaneous activity patterns of this sort have been characterized in 2D neural cell cultures using various methods, in studies which investigated the activity at the cellular level (using intracellular electrodes) and as a population (using extracellular electrodes; Marom and Shahaf, 2002; Wagenaar et al, 2005; Shein et al, 2008). High-density 2D cultures of dissociated cortical cells tend to exhibit spontaneous activity patterns that develop in a stereotyped manner.…”

“…3D cultures relevant for activity probing include networks embedded in a extracellular matrix (ECM)-like hydrogel scaffold (Irons et al, 2008; Iwashita et al, 2014) and 3D neuronal cultures devoid of ECM (Bosi et al, 2015), which can be probed using 3D electrode arrays (Musick et al, 2009) or optical (Pautot et al, 2008) approaches. Optical imaging methods, particularly calcium imaging (Cossart et al, 2005; Shein et al, 2008; Herzog et al, 2011; Dana et al, 2014), support neuronal population activity recording at cellular resolution, and avoid the spike sorting problem associated with extracellular electrodes. The optical alternative can also be used to show correlations between neuron activity and morphology (Cossart et al, 2005) and is particularly well suited for distributed 3D populations (Edelman and Keefer, 2005; Irons et al, 2008; Baker and Chen, 2012; Lai et al, 2012; Dana et al, 2014; Bosi et al, 2015; Ulloa Severino et al, 2016).…”

Synchronous Bursts on Scale-Free Neuronal Networks with Attractive and Repulsive Coupling

“…Interestingly, it was reported that chemical and electrical synapses perform complementary roles in the synchronization of interneuronal networks [18]. Indeed, synchronization, information transmission and signal sensitivity on complex networks are currently hot topics in theoretical neuroscience [19,20], as evidenced by several recent studies that are devoted to the explorations of this subject [21][22][23][24][25][26][27][28][29][30][31][32].…”

Capturing remote activation of epilepsy source?

“…However, despite the fact that the origin, stability, and the functional role of the regime of spontaneous, irregularly repetitive PSs have been intensively studied [42,51,52,55,[58][59][60][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78], some key aspects, including a mechanistic explanation of PSs initiation and the nucleation effect, are yet to be unraveled. Fortunately, there are two fostering factors.…”