In the first part of this thesis, chapter 2, we review the mammalian visual system and the technologies for interfacing living neuronal networks.
Inchapter 3we study a state-of-the-art model of the early visual pathway to both develop a framework for the virtual connectome and to answer the question whether random wiring of the afferent visual pathway alone suffices to generate (i) feature selectivity and (ii) determine the functional architecture of the primary visual cortex. We find that weak orientation selectiv-ity can be generated in the random wiring scheme, but to obtain the specific layout observed across various mammalian species, the common design242, random wiring is insufficient. Self-organization of recurrent connections during development determining the preferred orientations remains the most likely candidate.
Next, in chapter 4, we will develop and assess two distinct approaches to construct an in vitro surrogate cortex. We first assess the viability of what we call virtual networks, realized by closed loop optogenetic connections162,348 between islands of individual neurons grown on multielectrode arrays (MEAs). Virtual networks are artificial neural networks with biological neurons as nodes. This approach seems promising because it allows in principle to construct arbitrary networks. We develop a protocol to yield≈60% populated islands on glass electrode arrays, but find that recording electrical activity is partially impaired by the required surface treatment of the glass chips. In the end, we observe only few islands with active electrodes.
Next, we design a system in which the local neuronal circuits are as realistic as possible. We find that cortical cultures can be set up with the same cell density and cellular content as the
input layer of sensory cortex. As these cultures are easier to produce on a large scale and show rich spontaneous activity, resembling the spontaneous activity in the young neocortex, our sec-ond strategy was to wire this surrogate cortex to a virtual sensory pathway. We implemented the virtual sensory pathwayin silico and interfaced the living neurons by a custom build digital phase-only holographic projection system.
Inchapter 5, we show details of the in silico visual pathway and its interface to the surro-gate cortex. We also find a generic scaling law for the layout of the early visual system which allows us to transform the visual pathway of a cat into that of a mouse. We connect these differ-ent pathways to the same target circuit of living neurons, providing for an internal control, and find that shrinking the visual system leads to a substantial loss of orientation selectivity in the afferent input, while surprisingly the total fraction of tuned cells changes little. The orientation bias of neurons in the limit of homogeneous inputs is generated by the recurrent network alone.
These cells are mostly simple cells with a small fraction of complex and direction tuned cells.
We also find cells with receptive fields composed of excitatory and inhibitory subregions, and these receptive fields have a typical spatial scale of≈1 mm, consistent with the generic scaling laws which we extracted earlier. Consistent with simple cells, the tuning can be predicted from the receptive field. The spatial arrangement of spontaneously tuned cells resembles a sparse salt and pepper pattern. This diversity of responses suggests that even in this most generic case, a recurrent circuit is sufficient to spontaneously generate a basic level of orientation selectivity.
Inchapter 6we will present a new method to manipulate the circuits in the surrogate cor-tex. The surrogate cortex is based on neuronal circuits generated in the absence of any input and the processes by which neurons wire into circuits are most likely partially activity dependent.
One way to manipulate the circuit’s connectome is thus by controlling the prevalent activity patterns during the course of circuit formation. In this chapter, we therefore ask whether the local circuits can be configured differently by supplying external inputs during development. We discover that external inputs during development change the collective dynamics of the surro-gate cortex massively. This chapter concludes the synthetic neurobiology part of this thesis.
Inchapter 7we further test the random wiring hypothesis using experimental data from cat and primate retinal ganglion cell mosaics. We compare it with an ensemble of bespoke ganglion cell mosaics that can theoretically seed iso-orientation domains in the visual cortex and find that the currently available data puts a strong quantitative constraint on the random wiring hypothesis and the idea that the layouts of domains are already encoded in the geometry of the retina. Considering the specificity and ubiquity of the common design, we next ask where the selective forces that favor the common design can break down. Using the reinvention of colorvi-sion among primates as natural experiment, we find a virtually identical layout of orientation domains in trichromatic macaque and color-blind owl monkeys, highlighting that orientation selectivity is truly a key player of functional cortical architecture, and likely orchestrates other functional aspects of the cortex.
In chapter 8 we reveal distortions in the peer review process, specifically showing that a scientist’s personal attributes matter. This chapter was originally motivated by personal obser-vations, and made rigorous by web-crawling the publicly available article web pages from the Frontiers Journal Series to obtain one of the largest datasets for the sociology of science available today including more than 175,000 individuals.
Finally, we review the content of this thesis inchapter 9together with an assessment of the merits of a synthetic neurobiology approach for the reconstitution of living neuronal circuits.
Chapter 2
Fundamentals
“Felix, qui potuit rerum cognoscere causas.”
Publius Vergilius Maro389: “Georgica”, Liber II, 490.
2.1 Content
Here, we review the building blocks of the early visual system and the currently available tech-nologies for interfacing living neuronal circuits. Its content serves as the foundation of the work in the following chapters. Reviewing these elements is critical to (1) construct thein vitro model of the visual pathway, (2) interpret our subsequent findings and (3) assess the potential merits of constructing a synthetic hybrid system of this specific sensory pathway.
The visual system is the paradigm of a sensory pathway and it is sequentially organized: A re-currently connected layer of neurons in the brain is processing the information arriving through the feed-forward neuronal pathway of retina and lateral geniculate nucleus, a thalamic process-ing station. Most importantly, we will introduce orientation selectivity, a key element of what is called the functional architecture of the visual cortex. It has recently been discovered that this functional architecture exhibits a set of quantitative layout rules, called the common design, that is likely to have been invented independently several times during mammalian evolution.