The first systematic analysis of synaptic potentials in the CNS was in the early 1950s by Eccles and associates, who recorded intracellularly from spinal motor neurons. When a microelectrode enters a cell, there is a sudden change in the potential recorded by the electrode, which is typically about −60 mV (Figure 21–3A). This is the resting membrane potential of the neuron. Two types of pathways—excitatory and inhibitory—impinge on the motor neuron.
When an excitatory pathway is stimulated, a small depolarization or excitatory postsynaptic potential (EPSP) is recorded. This potential is due to the excitatory transmitter acting on an ionotropic receptor, causing an increase in cation permeability. As additional excitatory synapses are activated, there is a graded summation of the EPSPs to increase the size of the depolarization (Figure 21–3A, spatial summation, middle). When a sufficient number of excitatory synapses are activated, the excitatory post-synaptic potential depolarizes the postsynaptic cell to threshold, and an all-or-none action potential is generated. Alternatively, if there is a repetitive firing of an excitatory input, the temporal summation of the EPSPs may also reach the action potential threshold (Figure 21–3A, right).
When an inhibitory pathway is stimulated, the postsynaptic membrane is hyperpolarized owing to the selective opening of chloride channels, producing an inhibitory postsynaptic potential (IPSP) (Figure 21–3B, middle). However, because the equilibrium potential for chloride (see Chapter 14) is only slightly more negative than the resting potential (~ −65 mV), the hyperpolarization is small and contributes only modestly to the inhibitory action. The opening of the chloride channel during the inhibitory postsynaptic potential makes the neuron “leaky” so that changes in membrane potential are more difficult to achieve. This shunting effect decreases the change in membrane potential during the excitatory postsynaptic potential. As a result, an EPSP
FIGURE 21–3 Postsynaptic potentials and action potential generation. A shows the voltage recorded upon entry of a micro-electrode into a postsynaptic cell and subsequent recording of a resting membrane potential of −60 mV. Stimulation of an excitatory pathway (E1, left) generates transient depolarization called an excitatory postsynaptic potential (EPSP). Simultaneous activation of multiple excitatory synapses (E1 + E2, middle) increases the size of the depolarization, so that the threshold for action potential generation is reached. Alternatively, a train of stimuli from a single input can temporally summate to reach the threshold (E1 + E2, right). B demonstrates the interaction of excitatory and inhibitory synapses. On the left, a suprathreshold excitatory stimulus (E3) evokes an action potential. In the center, an inhibitory pathway (I) generates a small hyperpolarizing current called an inhibitory postsynaptic potential (IPSP). On the right, if the previously suprathreshold excitatory input (E3) is given shortly after the inhibitory input (I), the IPSP prevents the excitatory potential from reaching threshold.
that evoked an action potential under resting conditions fails to evoke an action potential during the IPSP (Figure 21–3B, right). A second type of inhibition is presynaptic inhibition. It was first described for sensory fibers entering the spinal cord, where excitatory synaptic terminals receive synapses called axoaxonic synapses (described later). When activated, axoaxonic synapses reduce the amount of transmitter released from the terminals of sensory fibers. It is interesting that presynaptic inhibitory receptors are present on almost all presynaptic terminals in the brain even though axoaxonic synapses appear to be restricted to the spinal cord. In the brain, transmitter can spill out of the synapse and activate presynaptic receptors, either on the same synapse (autoreceptors) or on neighboring synapses.