Abstract
Analyzing the connectivity of neuronal networks, based on functional brain imaging data, has yielded new insight into brain circuitry, bringing functional and effective networks into the focus of interest for understanding complex neurological and psychiatric disorders. However, the analysis of network changes, based on the activity of individual neurons, is hindered by the lack of suitable meaningful and reproducible methodologies. Here, we used calcium imaging, statistical spike time analysis and a powerful classification model to reconstruct effective networks of primary rat hippocampal neurons in vitro. This method enables the calculation of network parameters, such as propagation probability, path length, and clustering behavior through the measurement of synaptic activity at the single-cell level, thus providing a fuller understanding of how changes at single synapses translate to an entire population of neurons. We demonstrate that our methodology can detect the known effects of drug-induced neuronal inactivity and can be used to investigate the extensive rewiring processes affecting population-wide connectivity patterns after periods of induced neuronal inactivity.
Highlights
The effects of drug-induced silencing of neuronal activity on the morphology and activity of single synapses have been studied for decades using the voltage-gated sodium channel blocker tetrodotoxin (TTX)[1,2,3,4]
Networks of neurons are studied across many different scales and are generally classified as anatomical, functional, or effective networks depending on the kind of relationship between network nodes that is described by the network edges[17]
Functional networks describe brain regions or cells that are simultaneously active during resting states[25,26] or a specific task[27,28] as for example shown by functional magnetic resonance imaging (MRI), electroencephalography[29,30], or magnetoencephalography[31,32]
Summary
The effects of drug-induced silencing of neuronal activity on the morphology and activity of single synapses have been studied for decades using the voltage-gated sodium channel blocker tetrodotoxin (TTX)[1,2,3,4]. TTX-induced synaptic inactivity induces growth of so-called active zones, characterized by larger numbers of docked vesicles, increased spontaneous release rates, and increases in the number of vesicles released upon a stimulus[7] Such alterations have been observed in the pathogenesis of tardive dyskinesia[8], glaucoma[9], neuropathic pain[10,11], and drug addiction[12,13,14] and withdrawal[15,16]. On the level of single cells, effective networks represent the actual propagation of action potentials They are the resulting information processing landscape based on synaptic (e.g. post-synaptic excitability) and cellular (e.g. dendritic spine density) characteristics. Effective connectivity has been investigated in the context of epilepsy[35,47] and Sanfilippo syndrome[48]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
