Cholinergic Modulation of Proteinoid Microsphere Networks as Prebiotic Depression Models

Area of Science:

• Origin of Life Research
• Neuroscience
• Physical Chemistry

Background:

• Mood disorders' molecular origins are complex and poorly understood.
• Proteinoid microspheres, cell-like structures from amino acids, exhibit spontaneous electrical activity.
• Nicotine, a cholinergic agonist, is linked to depression.

Purpose of the Study:

• To investigate the effect of nicotine on prebiotic neural network models (proteinoid microspheres).
• To characterize the electrochemical and dynamical changes induced by nicotine.
• To explore the physicochemical underpinnings of depression-like states.

Main Methods:

• Electrochemical characterization using impedance spectroscopy and cyclic voltammetry.
• Long-duration monitoring of microsphere electrical activity (>75 h).
• Equivalent circuit modeling and fractal dimension analysis.

Main Results:

• Nicotine induced a 'depressive' state, marked by hyperactive but low-fidelity spiking, not reduced activity.
• Degraded signal quality, increased firing frequency (52%), reduced amplitude precision, and phase-space expansion (1500-fold) were observed.
• Nicotine decreased membrane charge-transfer resistance, increased capacitance, and shifted dynamics from self-organized criticality to stochasticity.

Conclusions:

• Cholinergic modulation of excitability is a fundamental physicochemical interaction, not exclusive to evolved biological receptors.
• Depression may represent a breakdown in thermodynamic self-organization, shifting information processing from order to disorder.
• These physicochemical effects may represent a precursor to nervous system function and mood regulation, originating in the prebiotic era.