Biomedical Engineering Reference
In-Depth Information
After the initial stage of intense neurite formation, the neuronal cell bodies
start to aggregate into packed clusters. The clustering of cells is accompanied
by absorption of branches, as well as the formation of whole neurites, rear-
rangements of neurites, and fusion of parallel neurites. The somata can then be
observed to migrate along newly formed bundles toward one another. The
clustering of neurons is essential in maintaining the synchronous oscillatory
activity. This is a characteristic of both the brain circuits and can be observed
in vitro environments outside the brain.
In an in vitro environment, during the first week in culture, the neurons begin
to develop spontaneous activity. These activity patterns include complex
sequences of action potentials in isolation and in bursts that in vitro continue to
develop over the course of a month. Underlying these activity changes are
morphological changes of the neurons, allowing them to grow elaborate
dendritic and axonal arbors to form numerous synaptic connections. The glial
cells, if present in the dish, continue to divide and proliferate until limited by
contact inhibition or exogenous inhibitors of cell division. Glial cells provide
the necessary trophic factors for cultured neurons. There is also evidence that
direct contact between neurons and glial cells is crucial for neuronal survival
(potentially also playing a role in synaptic processing).
The final morphology of the neuronal networks is generated from two
opposing forces. There are benefits and drawbacks to the final morphology.
The formation of these networks is comprised of single neurons that grow
axons and highly branched dendritic trees to achieve maximum interconnected
networks. The benefit of this formation is that it allows information to flow and
eciently travel. The drawback with this formation is that developing extended
and vastly branched neurites has a high energetic cost. Hence, the structure of
the neuronal network results from interplay between these factors.
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The process
may be viewed as a small-scale illustration of what happens in the brain during
the continuous process of rewiring and establishing new connections. What
orchestrates such a complex and dynamic process is di
cult to imagine. What
we know today is that structural plasticity is directed by guiding molecules
released by target
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cells. External
stimulation generates new synaptic
connections between neurons.
Neuronal activity controls calcium influxes, directing the release of neuro-
trophic factors, movement of growth cones and synaptic differentiation. The
growth cone consists of filopodia and lamellipodia developed by F-actins and
microtubules. The cellular spatial organization inside the growth cone changes
continuously via external cues by the phenomenon of contact guidance.
9,10
The
membranes, which are the natural substrate for cells, possess a complex three-
dimensional (3D) topography, consisting of nanometer-sized features. These
features alter the cellular adhesion, which enables spreading, migration and
proliferation. The fact that this organization can occur in a Petri dish (in vitro
environment outside the brain) demonstrates that the presence of a distant
regulatory source is not necessary and that self-organizing abilities are
embedded in each growing cell. This explains the remarkable fluidity and
plasticity of the brain structure on a macroscopic scale.
