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18/19 November 2022 - Teatro Olimpico, ROME
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From neonatology to the molecular based of the transduction from luminous impulse to nervous impulse

  • Spiga T.,
ABSTRACT

1. Introduction

In 1972 Massimo Fagioli wrote Death instinct and knowledge in which he states that the activation of nervous system, and therefore of human thought, must be credited to the first photon that hits the retina rather than to the first breath 1-2-3-4.

The studies reported in this abstract lay the molecular bases supporting the theory he postulated.

2. Embryology of the central nervous system (CNS) 

At the beginning of the 3rd week of gestation, the CNS appears as ectodermal thickening.Subsequently its lateral margins rise up to form neural folds. With further development, the lateral margins continue to rise and approach the midline and, at the end, joining together, generating neural tube. The fusion proceeds in a cranio-caudal direction. Final closure of cranial neuroporeoccurs on day 25 and, approximately two days later, the closure of caudal neuropore occurs5.The subplate is a transient compartment of fetal telencephalic wall and contains a population of neurons which play a key role in the normal development of the cerebral cortical structure and in its connectivity. In particular, it allows the connections that are essential to connect the CNS to the periphery6.

The functional maturation of the subplate at the 23rd -24th week corresponds to the age currently considered as the minimum threshold for the survival of premature babies. During the second trimester, the subplate significantly increases in thickness and complexity and, at birth, the infant’s brain has a near-adult number of neurons but an immature set of connections7.

The first respiratory action must necessarily be preceded by the elimination of the liquid from the lungs. This step begins prior to the first respiratory action making it possible and also requires anactive contraction of the diaphragm. This is controlled by multiple stimuli, all originating from different areas of the CNS, and involves many neural arches but also motor outputs to there spiratory and facial muscles. All these signals are integrated, modulated and transmitted to the effector organs from the brain8. The evidence of a series of neurological events that occur prior to the first breath opens the way for the primacy of the CNS at birth, which would cause the activation of all the procedures treated so far9.

Birth generates a transition between the fetal-state and the neonatal-state and the excitation of the aforementioned circuits is probably partly due to the activation of the noradrenergic system in the brain.

GABA plays an important role in the transition from fetal to neonatal life. The subplate induces differentiation towards the GABAergic line where GABA is considered the dominant excitatory neurotransmitter during intrauterine life. Shortly before birth, GABA becomes the main inhibitory neurotransmitter by completely modifying the brain’s electrical activity.The switch that changes GABA from fetal excitatory to neonatal inhibitory function is triggered by a mild retinal stimulation6.

3. Light and its retinal stimulation 

Humans has two different cell types for receiving light: rods and cones. In the process of vision are involved the GPCR rhodopsin, in the rods, and opsins, in the cones, which are activated by light10. In GPCRs, the external signal is a small molecule that binds to the receptor embedded in the membrane and causes a conformational change.

The protagonist responsible for the absorption of light, the 11-cis-retinal, is linked to each opsin.After the absorption of a photon, the 11-cis-retinal undergoes photoisomerization generating the 11-trans-retinal and induces a corresponding change in the opsin from its inactive to active conformation. The active form recruits and binds intracellular G proteins, activating the visual signal cascade that culminates in an electrical impulse to the visual cortex of the brain. The systemis so sensitive that it is able to detect a single photon11-12.

The photon energy is stored by the chromophore in its highly distorted, all-trans form, in the same binding pocket where it resides in the dark as 11-cis-retinal.

Photoisomerization is a very fast process that occurs in a time interval of 200 fs13. Production of the primary photoproduct of ground state rhodopsin within just 200 fs suggests a fast and efficient photo-activated unidirectional reaction allowing ultra-fast conversion of photon energy into chemical energy14. Photo transduction is a process in which photoreceptors of the retina convert the absorption of light into a nervous signal. From the isomerization of retinal, the transduction process starts with the activation of the intracellular pathway, which causes a change in the membrane potential.

Since rhodopsins are G protein-coupled receptors, the first event of signal transduction is the recognition of a G protein which is called transducin.

When rhodopsin is activated by light it binds to transducin, which in turn is linked to GDP. This energy is transduced through the conformational change of rhodopsin and a subsequent conformational change in transducin, which causes the release of GDP and the binding with GTP15.

The first event of signal transduction is the release of one of the transducin subunits which subsequently activates the signal pathway culminating in the visual cortex.

In the final phase there will be an all-trans retinal release accompanied by the modification of some fundamental proteins. All this process is aimed to preparing the opsin for binding to the 11-cis-retinal, regenerating the basal state of rhodopsin which, at this point, will be ready for a new phototransduction cycle.

4. Conclusions

On the basis of what is reported in this work, it can be seen that Massimo Fagioli’s intuition is endorsed by neonatology and molecular biology and it is now almost certain that the first event that activates the nervous system, and therefore human thought, is just the photon that hits retina.

Bibliography

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