Network synchronization in hippocampal neurons

Abstract

Oscillatory activity is widespread in dynamic neuronal networks. The main paradigm for the origin of periodicity consists of specialized pacemaking elements that synchronize and drive the rest of the network; however, other models exist. Here, we studied the spontaneous emergence of synchronized periodic bursting in a network of cultured dissociated neurons from rat hippocampus and cortex. Surprisingly, about 60% of all active neurons were self-sustained oscillators when disconnected, each with its own natural frequency. The individual neuron's tendency to oscillate and the corresponding oscillation frequency are controlled by its excitability. The single neuron intrinsic oscillations were blocked by riluzole, and are thus dependent on persistent sodium leak currents. Upon a gradual retrieval of connectivity, the synchrony evolves: Loose synchrony appears already at weak connectivity, with the oscillators converging to one common oscillation frequency, yet shifted in phase across the population. Further strengthening of the connectivity causes a reduction in the mean phase shifts until zerolag is achieved, manifested by synchronous periodic network bursts. Interestingly, the frequency of network bursting matches the average of the intrinsic frequencies. Overall, the network behaves like other universal systems, where order emerges spontaneously by entrainment of independent rhythmic units. Although simplified with respect to circuitry in the brain, our results attribute a basic functional role for intrinsic single neuron excitability mechanisms in driving the network's activity and dynamics, contributing to our understanding of developing neural circuits.neuron | network | oscillator | synchrony | persistent Na current P eriodicity emerges as a key physiological characteristic at all levels of neuronal activity, from the dynamics of neurons at subthreshold potentials (1, 2), through rhythmic neuronal ensembles within local networks, and all of the way up to global oscillations measured by electroencephalography (EEG) (3). The range of observed frequencies is surprisingly wide, from the millisecond range typical for interspike intervals all of the way to several seconds in the case of slow EEG. Over the years, accumulating evidence and theory have attributed different mechanisms for the origin of each measured periodic activity. Within local networks, the role of known collective mechanisms for periodicity, such as the balance between excitatory and inhibitory neurons and recurrent network architecture (4-6), is often contrasted with single neuron contributions, for example, the role of pacemaker neurons in oscillatory network dynamics (7). Although the physiological properties of single neurons are diverse and well documented (2, 8), their role in emergent network oscillations was predicted theoretically (9), but has not been observed experimentally. This contribution may involve a subtle interplay between intrinsic excitability and network connectivity (10, 11).The connectivity and excitability together determi...

Vibrational Profiling of Brain Tumors and Cells

“…Interestingly, this correlates with reported high amplitude theta oscillations in the hippocampus of neonatal rat pups 57-60 which have been detected even as early as 2-days old 61. Similarly, synchronous bursting rates (1-10 Hz) have been reported in hippocampal cultures by our collaborators and other groups 62-64. Conversely, very little is reported on spontaneous synchronized cell firing within the cerebellum of newborn rat pups.…”

High sensitivity of spontaneous spike frequency to sodium leak current in a Lymnaea pacemaker neuron

“…Leak current is a functional component of the background conduction necessary to establish resting membrane potential or pacemaker potential (Hodgkin & Huxley, , ). It regulates network oscillation (Koizumi & Smith, ; Pang et al ., ; Zhao et al ., ; Penn et al ., ), cell excitability (Brickley et al ., ; Lutas et al ., ), and pacemaker activities (Hagiwara et al ., ; Liu et al ., ; Jackson et al ., ; Pena & Ramirez, ; Tazerart et al ., ; Ptak et al ., ; Khaliq & Bean, ; Koizumi et al ., ). There are both K + and Na + leak conductances in neurons, with the K + component playing a predominant role.…”

Role of human induced pluripotent stem cell-derived spinal cord astrocytes in the functional maturation of motor neurons in a multielectrode array system

“…Bursts were defined as activity with >4 spikes/0.1 sec. Hypersynchronous (or "network") bursts were defined when over 60% of active electrodes fired within one 20-ms bin, as previously described 17 . Spike trains were exported into an HDF5 format and further analyzed using MEAnalyzer 18 .…”