Emergent Properties of in silico Synaptic Transmission in a Model of the Rat Neocortical Column

The cerebral cortex occupies nearly 80% of the entire volume of the mammalian brain and is thought to subserve higher cognitive functions like memory, attention and sensory perception. The neocortex is the newest part in the evolution of the cerebral cortex and is perhaps the most intricate brain region ever studied. The neocortical microcircuit is the smallest Œecosystem‚ of the neocortex that consists of a rich assortment of neurons, which are diverse in both their morphological and electrical properties. In the neocortical microcircuit, neurons are horizontally arranged in 6 distinct sheets called layers. The fundamental operating unit of the neocortical microcircuit is believed to be the Neocortical Column (NCC). Functionally, a single NCC is an arrangement of thousands of neurons in a vertical fashion spanning across all the 6 layers. The structure of the entire neocortex arises from a repeated and stereotypical arrangement of several thousands of such columns, where neurons transmit information to each other through specialized points of information transfer called synapses. The dynamics of synaptic transmission can be as diverse as the neurons defining a connection and are crucial to foster the functional properties of the neocortical microcircuit. The Blue Brain Project (BBP) is the first comprehensive endeavour to build a unifying model of the NCC by systematic data integration and biologically detailed simulations. Through the past 5 years, the BBP has built a facility for a data-constraint driven approach towards modelling and integrating biological information across multiple levels of complexity. Guided by fundamental principles derived from biological experiments, the BBP simulation toolchain has undergone a process of continuous refinement to facilitate the frequent construction of detailed in silico models of the NCC. The focus of this thesis lies in characterizing the functional properties of in silico synaptic transmission by incorporating principles of synaptic communication derived through biological experiments. In order to study in silico synaptic transmission it is crucial to gain an understanding of the key players influencing the manner in which synaptic signals are processed in the neocortical microcircuit - ion channel kinetics and distribution profiles, single neuron models and dynamics of synaptic pathways. First, by means of exhaustive literature survey, I identified ion channel kinetics and their distribution profiles on neocortical neurons to build in silico ion channel models. Thereafter, I developed a prototype framework to analyze the somatic and dendritic features of single neuron models constrained by ion channel kinetics. Finally, within a simulation framework integrating the ion channels, single neuron models and dynamics of synaptic transmission, I replicated in vitro experimental protocols in silico, to characterize the transmission properties of monosynaptic connections. These synaptic connections, arisin