Neuromodulators are special chemicals in the brain that help control how signals are sent between nerve cells. They do this in a few different ways:

1. Receptor Interaction:

   • Neuromodulators connect with specific spots on cell surfaces called G-protein-coupled receptors (GPCRs).
   • When they bind to these receptors, they can change how ions move in and out of the cell and affect the release of other important chemicals called neurotransmitters.

2. Second Messenger Systems:

   • When GPCRs are activated, they kick off a chain reaction involving second messengers, like cAMP, IP3, and calcium.
   • These systems can change the way signals are sent at about 80% of the connections between nerve cells (synapses).

3. Synaptic Plasticity:

   • Neuromodulators are key players in processes called long-term potentiation (LTP) and long-term depression (LTD).
   • It's estimated that around 40% of the changes in how synapses work in the brain are influenced by neuromodulators.

Together, these processes help adjust how well nerve cells communicate and how easily they can get excited.