An inhibitory interneuron synapses directly onto the soma of a pyramidal neuron, while another inhibitory synapse is located on a distal dendrite. All else being equal, which inhibitory synapse is more effective at suppressing neuronal firing, and why?
AThe distal dendritic synapse, because it intercepts excitatory inputs arriving from the dendritic tree before they summate
BThe somatic synapse, because it can shunt excitatory currents arriving from the entire dendritic tree before they reach the axon initial segment
CBoth synapses are equally effective, since inhibitory current magnitude depends only on chloride conductance
DThe somatic synapse, because the soma contains a higher density of GABA_A receptors than dendrites
Location matters enormously for inhibitory efficacy. An IPSC on the soma or axon initial segment is positioned to veto excitatory inputs arriving from the entire dendritic arbor — all those EPSCs must pass through the soma to reach the axon hillock, and the somatic IPSC provides a low-resistance shunt at exactly that bottleneck. A distal dendritic IPSC only affects inputs arriving from that dendritic branch. Shunting inhibition — where the increased conductance diverts excitatory current to the chloride reversal potential — is often more important than hyperpolarization per se, especially when the chloride equilibrium potential is near resting potential.
Question 2 Multiple Choice
A single EPSC at one synapse typically produces only a 0.5–1 mV depolarization at the soma. What does this imply about how a neuron decides to fire an action potential?
ANeurons rarely fire because individual EPSCs are too small to matter; firing only occurs during intense sensory stimulation
BThe neuron must summate many EPSCs — either from multiple near-simultaneous synapses (spatial summation) or repeated firing from the same synapse (temporal summation) — to reach threshold
CA single EPSC is sufficient if it arrives at the axon hillock directly rather than through dendrites
DNeurons compensate by increasing channel density at the synapse to amplify individual EPSCs
A single EPSC produces a tiny EPSP (~0.5–1 mV) because each synaptic event opens only a small number of channels. Reaching the ~15 mV depolarization needed for an action potential requires summation. Spatial summation occurs when multiple synapses fire at nearly the same time — their EPSPs add at the soma. Temporal summation occurs when the same synapse fires repeatedly before the membrane potential has recovered — each successive EPSP adds to the last. This summation requirement means the neuron effectively computes a weighted average over its inputs, which is why individual neurons can function as computational units that integrate information from hundreds of sources.
Question 3 True / False
Inhibitory postsynaptic currents can suppress neuronal firing even without measurably hyperpolarizing the membrane potential, through shunting inhibition.
TTrue
FFalse
Answer: True
Shunting inhibition occurs when GABA_A receptor opening increases chloride conductance, pulling the membrane potential toward the chloride reversal potential (~−75 mV). If the cell is already near rest (−70 mV), this may produce only a few mV of hyperpolarization — imperceptible in many recordings. But the key effect is the increase in membrane conductance: by providing a low-resistance pathway to −75 mV, the shunt 'diverts' excitatory currents that would otherwise depolarize the membrane. Nearby EPSCs lose much of their effectiveness because the increased conductance dissipates their current before it can raise membrane voltage. This is particularly powerful when inhibitory synapses are near the axon initial segment.
Question 4 True / False
In mature adult neurons, GABA_A receptor activation generally produces inhibition by driving the membrane potential toward a hyperpolarized chloride reversal potential.
TTrue
FFalse
Answer: False
This is only true for mature neurons. In immature developing neurons (and in some adult neurons), the chloride transporter NKCC1 predominates over KCC2, maintaining high intracellular chloride concentrations. As a result, the chloride reversal potential is more depolarized than the resting potential, and GABA_A activation causes chloride to flow OUT of the cell — producing depolarization rather than hyperpolarization. GABA is therefore excitatory early in development. This developmental switch (from KCC2 maturation progressively shifting the chloride equilibrium) is why neonatal seizures can be paradoxically worsened by benzodiazepines that potentiate GABA_A, an important clinical consideration.
Question 5 Short Answer
Why does the TIMING of an IPSC relative to incoming EPSCs matter for whether excitation succeeds in triggering an action potential? Explain with reference to the neuron's integration process.
Think about your answer, then reveal below.
Model answer: The neuron integrates currents at each moment in time. An IPSC that arrives during or just before a volley of EPSCs can shunt or cancel those excitatory currents — the chloride conductance is elevated exactly when the excitatory current is trying to raise membrane voltage, so the two largely cancel. But an IPSC that arrives too early (before the EPSCs) or too late (after the neuron has already depolarized toward threshold) has minimal effect on whether the action potential occurs. Neural circuits exploit this temporal precision: inhibitory interneurons with millisecond-accurate timing can gate specific windows of excitability, allowing the brain to select which excitatory inputs produce output and which are suppressed.
This timing sensitivity makes neural computation highly dynamic. The same set of excitatory inputs can produce very different outputs depending on whether and when inhibitory signals arrive. Feedforward inhibition — where an input activates both excitatory and inhibitory cells, with the inhibitory cells delaying excitation of the target — implements a coincidence detection window: only inputs arriving within the narrow window before inhibition closes off excitability will drive firing. This is a key mechanism for temporal coding and pattern selectivity in neural circuits.