Relationship Among EPSP, IPSP, Action Potentials, and Synaptic Decision Making

Sherrington's Inference of Inhibitory Synapses and Neuromuscular Control

  • Mechanism of Reflexive Inhibition:

    • When a flexor muscle is excited during a reflex contraction, the probability of excitation in the paired extensor muscle on the same limb simultaneously decreases.

    • Charles Sherrington inferred that a sensory input exciting a motor neuron connected to the flexor muscle simultaneously engaged an interneuron that inhibited the motor neuron connected to the extensor muscle.

  • Role of Interneurons:

    • Interneurons serve as critical computational relays that convert a single incoming excitatory signal into dual outputs: excitation to an agonist muscle and inhibition to an antagonist muscle.

Relationship Among EPSP, IPSP, and Action Potentials

  • Circuit Dynamics and Temporal Processing:

    • Neuronal circuits use specific wiring patterns to control the precise timing and duration of neural responses.

    • Microcircuit Example (Neural Wiring):

    • Neuron 1 forms a direct excitatory synapse with Neuron 3.

    • Neuron 1 also forms an excitatory synapse with Neuron 2.

    • Neuron 2 (an inhibitory interneuron) forms an inhibitory synapse with Neuron 3.

    • Temporal Sequence of Signals:

    • The excitatory message from Neuron 1 arrives at Neuron 3 first because it traverses only one synapse.

    • Signal transmission through any synapse causes a brief delay. Thus, the inhibitory message from Neuron 2 reaches Neuron 3 slightly later because it traverses two synapses.

    • Functional Outcome: Neuron 3 experiences a transient, brief excitation (excitatory postsynaptic potential or EPSP) that is rapidly halted by the delayed inhibitory postsynaptic potential (IPSP) from Neuron 2.

  • Characteristics of Inhibitory Neurons:

    • Inhibitory interneurons are typically small in size.

    • Their primary function in microcircuits is to regulate, curtail, and fine-tune the duration and timing of neural activity.

Synaptic Wiring Diagrams and Combinatorial Logic

Synaptic wiring diagrams determine postsynaptic responses by performing elementary combinatorial logic functions, operating in a manner analogous to biological logic gates.


Synaptic wiring diagrams illustrating neuronal circuit logic and connections

  • "A or B" Response Circuit:

    • Threshold: Cell X has an excitation threshold of 11 (Threshold=1\text{Threshold} = 1).

    • Inputs: Cell A contributes an excitatory value of +1+1; Cell B contributes an excitatory value of +1+1.

    • Function: An action potential in either Cell A (+1≥1+1 \ge 1) or Cell B (+1≥1+1 \ge 1) produces an EPSP sufficient to reach Cell X's threshold.

    • Output: Cell X fires an action potential if Cell A OR Cell B is active.

  • "A and B" Response Circuit:

    • Threshold: Cell X has an excitation threshold of 22 (Threshold=2\text{Threshold} = 2).

    • Inputs: Cell A contributes an excitatory value of +1+1; Cell B contributes an excitatory value of +1+1.

    • Function: Neither Cell A alone (+1<2+1 < 2) nor Cell B alone (+1<2+1 < 2) can depolarize Cell X to its threshold.

    • Spatial Summation: Simultaneous firing from both Cell A and Cell B combines their individual EPSPs (+1+1=+2+1 + 1 = +2) to reach the excitation threshold.

    • Output: Cell X fires an action potential only if Cell A AND Cell B are active together.

  • "A and B if not C" Response Circuit:

    • Threshold: Cell X has an excitation threshold of 22 (Threshold=2\text{Threshold} = 2).

    • Inputs: Cell A contributes +1+1, Cell B contributes +1+1, and Cell C contributes an inhibitory value of −1-1.

    • Function: Excitation from both Cell A and Cell B summates (+1+1=+2+1 + 1 = +2) to meet Cell X's threshold. However, if Cell C is active at the same time, its inhibitory input cancels out part of the depolarization (+1+1−1=+1+1 + 1 - 1 = +1), dropping the total potential below threshold.

    • Output: Cell X fires an action potential if Cell A AND Cell B are active, UNLESS Cell C is active.

Complexities of Synaptic Integration and Non-Additive Effects

  • Limitations of Classical Binary Models:

    • Historical models proposed by Sherrington and early mathematical neuroscientists treated synapses as simple binary (on/off) switches.

    • Biological synapses exhibit far greater operational complexity than simple binary logic.

  • Variability in Synaptic Duration and Nonlinear Summation:

    • Synapses vary greatly in the duration of their postsynaptic effects.

    • Synaptic inputs interact in complex, non-additive ways rather than simple linear arithmetic.

    • The combined physiological effect of two simultaneous synaptic inputs can be significantly greater than double (hyper-additive) or less than double (sub-additive) the effect of either synapse active individually (Silver, 2010).

Spontaneous Firing Rate and Modulation of Neural Activity

  • Concept of Spontaneous Firing Rate:

    • Most central nervous system neurons exhibit a spontaneous firing rate, generating a continuous, periodic stream of action potentials even in the total absence of external synaptic input.

  • Bidirectional Modulation:

    • EPSPs: Increase the frequency of action potential firing above the baseline spontaneous rate.

    • IPSPs: Decrease the frequency of action potential firing below the baseline spontaneous rate.

  • Quantitative Example:

    • Assume a neuron has a baseline spontaneous firing rate of 10 action potentials per second10\,\text{action potentials per second}.

    • A stream of incoming EPSPs can increase the overall firing frequency to 15 action potentials per second15\,\text{action potentials per second} or higher.

    • A preponderance of incoming IPSPs can suppress the overall firing frequency to 5 action potentials per second5\,\text{action potentials per second} or lower.

Module 3.1 In Closing: The Neuron as Decision Maker

  • Axonal Transmission vs. Synaptic Processing:

    • Transmission along an axon merely propagates an electrical signal from one anatomical location to another without modifying its content.

    • Synapses serve as the fundamental sites of dynamic computational processing and signal integration in the nervous system.

  • Synaptic Decision Integration:

    • EPSPs and IPSPs perform a cellular "decision-making" process by algebraically integrating incoming inputs to determine whether the postsynaptic cell's membrane potential will reach threshold and fire an action potential.

Stop & Check Questions and Discussion

  • Question 3: What was Sherrington's evidence for inhibition in the nervous system?

    • Answer: Sherrington observed that a reflex stimulus triggering contraction of a flexor muscle simultaneously caused relaxation/inhibition of the paired extensor muscle in the same limb. From this reciprocal innervation, he inferred that an axon sending an excitatory message to the flexor muscle also sent an inhibitory message to the extensor muscle via an interneuron.

  • Question 4: What ion gates in the membrane open during an EPSP? What gates open during an IPSP?

    • Answer: During an EPSP (excitatory postsynaptic potential), sodium (Na+\text{Na}^+) gates open in the membrane. During an IPSP (inhibitory postsynaptic potential), potassium (K+\text{K}^+) or chloride (Cl−\text{Cl}^-) gates open.

  • Question 5: Can an inhibitory message flow along an axon?

    • Answer: No. Only action potentials propagate along an axon. Inhibitory messages take the form of IPSPs (inhibitory postsynaptic potentials), which are local, graded potentials that decay over time and distance across the soma and dendrites.