From single neurons in culture to the behaving animal; A quest for general motifs in neuronal systems' form and function.

Amir Ayali1, and Eshel Ben Jacob2
1Dept of Zoology, 2School of Physics and Astronomy
Tel Aviv University, 69978 Tel Aviv, Israel

The ultimate goal of our work is shedding light on some of the most fundamental principles responsible for the superior information processing capabilities and elevated plasticity of the brain.

The rationale behind the first part of this study was that basic precursors of these much quested principles might already be recognizable in simple invertebrate ganglia and spontaneously constructed networks composed of dissociated ganglion cells. We followed the neuronal growth process in culture, from isolated neurons to fully connected two-dimensional networks. The mature networks were mapped into connected graphs and their morphological features were used to characterize them as “Small-World Networks”. Such morphology enables rapid flow of information while maintaining the necessary wiring at a minimum. As part of the mechanism leading for this specific wiring diagram, we suggested two phases in the process of neuronal development resulting from interactions between form- and function-related factors. In the first, neurons are "tuned" to make first contact with neighboring cells as soon as possible, to minimize the time of growth. After neuronal interconnections are formed; a second branching strategy is adopted, favoring higher efficiency in length and volume.

Next, we set to accompany this description of the network morphological development by a parallel schema for development of electrical activity. Utilizing advanced multi-electrode-array technology we obtained long term simultaneously recordings of the electrical activity of a number of neurons at different locations in the culture. We showed that as networks develop sporadic spontaneous firing of the single neurons change into network activity with extremely complex temporal ordering. Fully mature, highly clustered networks exhibited rich temporal organizations: Distinct neural bursting events, each with its own characteristic time width and firing rate. Some neurons demonstrated hierarchical temporal ordering of bursts with different levels of inter-neuron synchronization.

By characterizing the activity of a distinct population of neurons under progressive levels of structural and functional constraints - from in vitro networks to the intact behaving animal - we demonstrated common motifs and identified trends of decreasing self-regulated complexity with increasing constraints. This important principle was supported and even better demonstrated by our recent results. We showed that the motor output of single unit oscillator in a complex system of coupled oscillators, the lamprey spinal cord, is characterized by high information capacity, i.e non-random variability or self regulated complexity. This endogenous high capacity is not always evident however, as it is restricted by morphological and functional constraints. It was experimentally revealed in vitro by blocking inter-segmental connections or by the appropriate modulatory conditions.

Hence, the potential of the elements of the nervous system to react with adaptive changes to intrinsic or extrinsic inputs, usually referred to as neuronal plasticity, is dependent on the increased morphological and functional complexity of neuronal networks. This in turn is correlated with high information processing capabilities and is the basis for our extreme behavioral plasticity.