[Frontiers In Bioscience, Landmark, 23, 1465-1486, March 1, 2018]

Up states-based developmental trajectories of the autistic cerebral cortex

Pavlos Rigas1

1Neurophysiology Lab, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Up and Down states of the cerebral cortex
3.1. Up and Down cortical states in vitro
3.2. The significance of Up and Down cortical states
4. The endophenotype
4.1. Spike and Wave Discharges: an endophenotype of epilepsy
4.1.1. Comparing ictogenesis in the cortex and studying mechanisms of epileptic activity
4.1.2. Screening for new antiepileptic drugs
5. Using spontaneous cortical Up and Down states to define critical periods for the development of autism
5.1. The Fmr1KO rodent model of autism
5.2. The developmental delay and heterochronicity of autism
5.3. Proposing a scheme for the neurobiological research of autism onset
5.3.1. Why record in vitro?
5.3.2. Why record in the interface chamber?The interface vs the submerged chamber
5.3.2.1. The submerged chamber pertains to intracellular rather than extracellular recordings
5.3.2.2. Space limitations of the submerged chamber
5.3.3. Why developmental trajectories?
5.3.4. The choice of ages
5.3.5. The choice of cortices
6. Conclusions
7. Acknowledgments
8. References

1. ABSTRACT

Autism is a severe neurodevelopmental disorder which affects information processing in the brain as the result of an abnormally developed cortex, brought about in ways that are poorly understood. The disorder is characterized by a very early onset, however, neurobiological studies at such young ages are often precluded in humans, thus, rendering respective research in appropriate animal models of the disease invaluable. The bulk of this research has focused mainly on how experimental models differ from normal rather than on when they begin to differ. However, understanding the neurobiology of autism at its onset is important for both describing and treating the disorder. Moreover, modelling human behaviours in animals is often very difficult. Therefore, in order for neurobiological research of autism to proceed it is essential to “decompose” the disorder into simpler, behavior-independent biological parameters. Here, I propose how network dynamics of local microcircuits may serve such a role in order to derive developmental trajectories of the cerebral cortex that will allow us to detect and investigate the disorder at its very beginning.

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Key Words: cerebral cortex, Up states, persistent activity, spontaneous, slow oscillations, development, autism, endophenotype, Review

Send correspondence to: Pavlos Rigas, Neurophysiology Lab, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece, Tel: 30 210 6597439, Fax: 30 210 6597545, E-mail: pavlosrigas@gmail.com