It is well known the electricity can be used to fire neurons. But can it be used to inhibit neuronal firing? This is in the context of extracellular stimulation. In extracellular stimulation, it is known that there is a threshold for stimulation and a threshold for damage(electroporation). Is there a threshold in between these two which inhibits neuron firing without any damage? Please provide reference for your answer.
Yes, but maybe not how you think.
It is important to recognize that voltages refer to potential differences. When we say the "a cell is at -65mV" for example, we mean "The potential difference across the cell's membrane to the extracellular space is -65mV." When you stimulate electrically, you create a transient electric field, whereby the extracellular space is no longer effectively isopotential.
Let's imagine for the sake of some neuron that this field strength is on the order of 40 mV across the membrane. If this electric field is perpendicular to some neuronal process, the voltage across the membrane will be about -105mV on one side, and -25mV on the other side. The -25mV side is now depolarized enough to open voltage gated sodium channels, and some current is flowing into the cell. Once the shock has passed, positive current will continue to flow through those open channels and open more channels. It doesn't matter much that the other side is transiently at -105mV, all that matters is that you opened a bunch of voltage gated sodium channels which starts a positive feedback loop.
Therefore, transient electrical simulation will almost always be excitatory. There are two exceptions:
1) Neurochemical inhibition. If you excite a particular brain region that is specifically inhabited by inhibitory projection neurons, you will primarily excite those inhibitory cells and therefore cause excitation elsewhere. Of course, in this case, the electrical stimulation itself is still directly exciting cells, they just happen to have inhibitory effects elsewhere.
2) Depolarization block. If you continually stimulate the same population of neurons with a high-frequency stimulation, you can put neurons in a state called "depolarization block." Voltage-gated sodium channels have a chance to inactivate whenever they are activated. If you inactivate enough channels, there aren't enough available to produce an action potential. Therefore, if you can keep a cell pretty much constantly depolarized by continually stimulating, you can prevent action potential propagation because too many of the voltage gated channels in the axon initial segment are inactivated.
In practice, focal electrical stimulation of the brain can be used to prevent or abrogate seizures. There is a device marketed for this.
NeuroPace's Responsive Neurostimulation System (RNS), an electrical-stimulation implant with two leads, each containing four electrodes, placed in the brain at the seizure focus. The RNS detects electrical activity that denotes the start of a seizure and delivers direct electrical stimulation to interrupt the activity and normalize the area.
It is not immediately obvious to me why this would work. The linked review describes how this was first observed empirically. My understanding is that the electrical stimulation causes polarization such that the nerve cannot immediately fire again as part of the epileptic focus. Sort of like a counter burn if you are fighting a wildfire.
In the 1990s, Durand and colleagues demonstrated success in suppressing spontaneous inter- ictal bursts in vitro by providing responsive stimulation directly in the epileptogenic region. Their result sug- gested that the mechanism for suppression is an inhibi- tory polarization caused by the transmembrane currents generated by the applied pulse. These trials in animals laid the groundwork for responsive stimulation therapy for epilepsy.
Neuron activity can indeed be inhibited with the correct type of electrical input stimulus.
In fact you can play around with various electrical signalling stimuli yourself, and observe the results not just for a single neuron but the entire network, yourself:
The link above is a simulation environment that tried to emulate neuronal activity based on user defined signalling stimuli. Not only can you inhibit signals, but you can totally control macroscopic behaviors: e.g. excitation of entire regions of a prototypical neuronal pathway.