Could sustained neuronal activity promote the formation or stabilization of inhibitory autapses?

Hi,

I am a Mechatronics Engineering student with no formal training in neuroscience. While exploring biologically inspired homeostatic mechanisms, I developed a hypothesis concerning inhibitory autapses.

Full hypothesis manuscript (PDF)

My central hypothesis is:

In neuron classes capable of inhibitory self-innervation, sustained elevated activity may, when self-apposition geometry and the biological context are permissive, increase the probability that a new self-contact forms or stabilizes and subsequently matures into a functional inhibitory autapse. The resulting autapse could then contribute negative feedback to neuronal excitability.

I found evidence supporting several individual parts of this idea: inhibitory autapses can suppress repetitive firing, neuronal activity can influence inhibitory synaptic plasticity and structural remodeling, and autaptic synaptogenesis can depend on biological context.

However, I have not found direct experimental evidence showing the complete causal step:

sustained elevated activity → formation or stabilization of a new inhibitory autapse.

My questions are:

  1. Is this hypothesis biologically plausible?

  2. Is there existing literature that directly tests this activity-to-autapse formation relationship?

  3. What would be the most appropriate experiment to test it?

I have attached a short hypothesis manuscript with the relevant references and proposed experimental test.

As my background is in mechatronics rather than neuroscience, I may have overlooked important mechanisms or literature, so critical feedback would be very valuable.

Thank you.