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Synaptic Triad of Fast Inhibition

(a) In the 'classical' pathway, multiple pyramidal cells (for simplicity, only one pyramidal cell is shown: P1) excite the inhibitory interneuron (I) at its soma. The interneuron then inhibits P3. In contrast, the 'synaptic triad' pathway proposed by Ren et al.3 involves P2 directly exciting the presynaptic inhibitory terminal of I, which in turn inhibits P3. Insets, organization and receptors of the synaptic contacts. The classical pathway is dominated by AMPA receptors (AMPAR), whereas the synaptic triad pathway is mediated by AMPA and kainate receptors (KR). The synaptic triad serially connects the P2 terminal (dark blue) to the GABA terminal, and thus indirectly to the soma of P3. Glutamatergic terminals might also monosynaptically excite both a pyramidal cell and an adjacent GABAergic bouton (light blue). (b) Functional consequences of these pathways. In the classical pathway (left), most pyramidal spikes (P1, top traces) produce subthreshold responses (I, middle, solid traces) with rare action potential responses (I, dashed trace), which trigger IPSPs in P3 (dashed trace). Synaptic delays increase from P1 to I to P3. In the synaptic triad pathway (right), single spikes from the pyramidal cell (P2, top traces) reliably, rapidly and strongly activate GABA synapses by directly depolarizing the GABAergic terminals, bypassing the cell body and dendrites of the interneurons, and causing IPSPs in target pyramidal cells (P3, bottom traces). This pathway would not directly depolarize the interneuron's soma (I, solid traces), but spikes might be triggered ectopically in GABAergic terminals. Note the differences in latencies of evoked responses in the classical versus synaptic triad pathways.

Web Resource: www.nature.com

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