Where does the initial action potential come from?

Question

When talking about action potentials we say that previous neurons caused an action potential in this neuron and that this neuron's action potential caused the same in further neurons.

But what is the origin of the first-ever action potential? Maybe in a living organism, there are no action potentials initially because the brain is always "on" and some part of the brain can always initiate processes in an other. If that is the case then how is the brain turned "on" initially? If not, then how does the first action potential get triggered from the "resting state"?

Answer 1

The very first evoked spike is most likely triggered by spontaneous activity, as even neurons with no synaptic connections are able to fire action potentials (Luhmann et al. 2016). Later in life neurons can be excited by the external environment through sensory stimulation. At some point the central pattern generators also mature and, either by network synchronization or tuning of intrinsic neuronal properties, are able to maintain a self-sustained activity pattern.

The question is then what triggers spontaneous activity during development? It has to do with calcium signaling, both exogenous and from internal stores. The exogenous trigger is paracrine release of GABA and glutamate before the formation of synapses (Rosenberg and Spitzer 2011).

Answer 2

The first spikes are typically from sensory organs and arise from depolarization of the sensory cell by an external stimulus. This can happen in many different ways, but common for all sensory cells is that there are specialized ion channels that will open in response to the right stimulus (termed the adequate stimulus). Chemoreceptors, involved in taste and smell, have membrane channels that work in the same way as postsynaptic transmitter channels, except that they are triggered by whatever molecule or modecule-group they are sensitive to, rather than sensitive to transmitter molecules. Binding of the right molecule to the receptor channel (either directly, or indirectly through second-messenger systems) will lead to an influx of typically Ca, causing a depolarizing receptor potential, which triggers the action potential. Mechanoreceptors have membrane channels that respond by opening for Ca-influx simply by the physical deformation of the membrane (through an extremely diverse range of modifications and elaborate support structures). Sound-sensitive receptors, such as hair cells in vertebrate ears, are also mechanoreceptors, stimulated by the motion caused by sound waves. Photo-receptors typically work by second-messenger systems internally in the receptor cell, where absorption of a photon by a suitable photopigment results in a cascade that leads to release of second messengers, such as GTP, which then bind and trigger the opening of Ca channels. An interesting special case is electroreceptors, found in sharks, many fish and al few mammals. Here the depolarization of the receptor cell is directly caused by the adequate stimulus: the change in the electric field.