Which of the following would increase the likelihood of an action potential

• Neurons communicate with each other via electrical events called ‘action potentials’ and chemical neurotransmitters.
• At the junction between two neurons (synapse), an action potential causes neuron A to release a chemical neurotransmitter.
• The neurotransmitter can either help (excite) or hinder (inhibit) neuron B from firing its own action potential.
• In an intact brain, the balance of hundreds of excitatory and inhibitory inputs to a neuron determines whether an action potential will result.

Neurons are essentially electrical devices. There are many channels sitting in the cell membrane (the boundary between a cell’s inside and outside) that allow positive or negative ions to flow into and out of the cell.

Normally, the inside of the cell is more negative than the outside; neuroscientists say that the inside is around -70 mV with respect to the outside, or that the cell’s resting membrane potential is -70 mV.

This membrane potential isn’t static. It’s constantly going up and down, depending mostly on the inputs coming from the axons of other neurons. Some inputs make the neuron’s membrane potential become more positive (or less negative, e.g. from -70 mV to -65 mV), and others do the opposite.

These are respectively termed excitatory and inhibitory inputs, as they promote or inhibit the generation of action potentials (the reason some inputs are excitatory and others inhibitory is that different types of neuron release different neurotransmitters; the neurotransmitter used by a neuron determines its effect).

Action potentials are the fundamental units of communication between neurons and occur when the sum total of all of the excitatory and inhibitory inputs makes the neuron’s membrane potential reach around -50 mV (see diagram), a value called the action potential threshold.

Neuroscientists often refer to action potentials as ‘spikes’, or say a neuron has ‘fired a spike’ or ‘spiked’. The term is a reference to the shape of an action potential as recorded using sensitive electrical equipment.

A neuron spikes when a combination of all the excitation and inhibition it receives makes it reach threshold. On the right is an example from an actual neuron in the mouse's cortex. (Image: Alan Woodruff / QBI)

Synapses: how neurons communicate with each other

Neurons talk to each other across synapses. When an action potential reaches the presynaptic terminal, it causes neurotransmitter to be released from the neuron into the synaptic cleft, a 20–40nm gap between the presynaptic axon terminal and the postsynaptic dendrite (often a spine).

After travelling across the synaptic cleft, the transmitter will attach to neurotransmitter receptors on the postsynaptic side, and depending on the neurotransmitter released (which is dependent on the type of neuron releasing it), particular positive (e.g. Na+, K+, Ca+) or negative ions (e.g. Cl-) will travel through channels that span the membrane.

Synapses can be thought of as converting an electrical signal (the action potential) into a chemical signal in the form of neurotransmitter release, and then, upon binding of the transmitter to the postsynaptic receptor, switching the signal back again into an electrical form, as charged ions flow into or out of the postsynaptic neuron.

An action potential, or spike, causes neurotransmitters to be released across the synaptic cleft, causing an electrical signal in the postsynaptic neuron. (Image: By Thomas Splettstoesser / CC BY-SA 4.0)

Video: Action potentials in neurons

Concepts and definitions

Axon – The long, thin structure in which action potentials are generated; the transmitting part of the neuron. After initiation, action potentials travel down axons to cause release of neurotransmitter.

Dendrite – The receiving part of the neuron. Dendrites receive synaptic inputs from axons, with the sum total of dendritic inputs determining whether the neuron will fire an action potential.

Spine – The small protrusions found on dendrites that are, for many synapses, the postsynaptic contact site.

Membrane potential – The electrical potential across the neuron's cell membrane, which arises due to different distributions of positively and negatively charged ions within and outside of the cell. The value inside of the cell is always stated relative to the outside: -70 mV means the inside is 70 mV more negative than the outside (which is given a value of 0 mV).

Action potential – Brief (~1 ms) electrical event typically generated in the axon that signals the neuron as 'active'. An action potential travels the length of the axon and causes release of neurotransmitter into the synapse. The action potential and consequent transmitter release allow the neuron to communicate with other neurons.

Neurotransmitter – A chemical released from a neuron following an action potential. The neurotransmitter travels across the synapse to excite or inhibit the target neuron. Different types of neurons use different neurotransmitters and therefore have different effects on their targets. 

Synapse – The junction between the axon of one neuron and the dendrite of another, through which the two neurons communicate.

QBI research

QBI Laboratories working on neurons and neuronal communication: Professor Stephen Williams, Professor Pankaj Sah

QBI Laboratories working on synapses: Dr Victor Anggono, Professor Joseph Lynch, Professor Frederic Meunier

Postsynaptic conductance changes and the potential changes that accompany them alter the probability that an action potential will be produced in the postsynaptic cell. At the neuromuscular junction, synaptic action increases the probability that an action potential will occur in the postsynaptic muscle cell; indeed, the large amplitude of the EPP ensures that an action potential always is triggered. At many other synapses, PSPs actually decrease the probability that the postsynaptic cell will generate an action potential. PSPs are called excitatory (or EPSPs) if they increase the likelihood of a postsynaptic action potential occurring, and inhibitory (or IPSPs) if they decrease this likelihood. Given that most neurons receive inputs from both excitatory and inhibitory synapses, it is important to understand more precisely the mechanisms that determine whether a particular synapse excites or inhibits its postsynaptic partner.

The principles of excitation just described for the neuromuscular junction are pertinent to all excitatory synapses. The principles of postsynaptic inhibition are much the same as for excitation, and are also general. In both cases, neurotransmitters binding to receptors open or close ion channels in the postsynaptic cell. Whether a postsynaptic response is an EPSP or an IPSP depends on the type of channel that is coupled to the receptor, and on the concentration of permeant ions inside and outside the cell. In fact, the only factor that distinguishes postsynaptic excitation from inhibition is the reversal potential of the PSP in relation to the threshold voltage for generating action potentials in the postsynaptic cell.

Consider, for example, a neuronal synapse that uses glutamate as the transmitter. Many such synapses have receptors that, like the ACh receptors at neuromuscular synapses, open ion channels that are nonselectively permeable to cations. When these glutamate receptors are activated, both Na+ and K+ flow across the postsynaptic membrane. The reversal potential (Erev) for the postsynaptic current is approximately 0 mV, whereas the resting potential of neurons is approximately -60 mV. The resulting EPSP will depolarize the postsynaptic membrane potential, bringing it toward 0 mV. For the particular neuron shown in Figure 7.6A, the action potential threshold voltage is -40 mV. Thus, the EPSP increases the probability that the postsynaptic neuron will produce an action potential, defining this synapse as excitatory.

As an example of inhibitory postsynaptic action, consider a neuronal synapse that uses GABA as its transmitter. At such synapses, the GABA receptors typically open channels that are selectively permeable to Cl-. When these channels open, negatively charged chloride ions can flow across the membrane. Assume that the postsynaptic neuron has a resting potential of -60 mV and an action potential threshold of -40 mV, as in the previous example. If ECl is -70 mV, as is typical for many neurons, transmitter release at this synapse will inhibit the postsynaptic cell (because ECl is more negative than the action potential threshold). In this case, the electrochemical driving force (Vm - Erev) causes Cl- to flow into the cell, generating an outward PSC (because Cl- is negatively charged) and consequently a hyperpolarizing IPSP (Figure 7.6B). Because ECl is more negative than the action potential threshold, the conductance change arising from the binding of GABA keeps the postsynaptic membrane potential more negative than threshold, thereby reducing the probability that the postsynaptic cell will fire an action potential.

However, not all inhibitory synapses produce hyperpolarizing IPSPs. For instance, in the neuron just described, if ECl were -50 mV instead of -70 mV, then the synapse would still be inhibitory because the reversal potential of the IPSP remains more negative than the action potential threshold (-40 mV). Because the electrochemical driving force now causes Cl- to flow out of the cell, however, the IPSP is actually depolarizing (Figure 7.6C). Nonetheless, this depolarizing IPSP inhibits the postsynaptic cell because the cell's membrane potential is kept more negative than the threshold potential for action potential initiation. Another way to think about this peculiarity is that if another depolarizing input were to bring the cell's resting potential to -41 mV, just below threshold for firing an action potential, the opening of these GABA-activated channels would result in a hyperpolarizing current, bringing the membrane potential closer to -50 mV, the reversal potential for these channels. Thus, while EPSPs depolarize the postsynaptic cell, IPSPs can hyperpolarize or depolarize; indeed, an inhibitory conductance change may produce no potential change at all and still exert an inhibitory effect.

Although the particulars of postsynaptic action can be complex, a simple rule distinguishes postsynaptic excitation from inhibition: An EPSP has a reversal potential more positive than the action potential threshold, whereas an IPSP has a reversal potential more negative than threshold (Figure 7.6D). Intuitively, this rule can be understood by realizing that an EPSP will tend to depolarize the membrane potential so that it exceeds threshold, whereas an IPSP will always act to keep the membrane potential more negative than the threshold potential.