Figure 11. Schematic of PAD pathways mediating post-activation depression in the spinal cord.

Activation of flexor afferents (cyan) activates a tri-synaptic dorsal PAD pathway (glutamatergic interneuron dark grey, GABA_axo neuron red) with axo-axonic projections to an extensor afferent (dark green), activating nodal GABA_A receptors (red) and PAD in the extensor afferent. If the resulting PAD in the extensor afferent reaches sodium spiking threshold, PAD-evoked spikes (purple arrows) travel orthodromically to: 1) depolarize extensor afferent terminals, evoking an EPSP in the extensor motoneurons and a subsequent MSR/H-reflex; 2) activate a trisynaptic circuit containing GABAergic neurons that activate GABA_B receptors (black) on the extensor afferent terminal. Thus, the PAD-evoked spike in the extensor Ia afferent can produce early and late post-activation depression of subsequently activated MSRs/H-reflexes by: 1) decreased afferent excitability from collision of orthodromic action potentials with antidromic PAD-evoked spikes; 2) transmitter depletion following the PAD-evoked spike entering the extensor Ia afferent; and/or 3) inhibition of the afferent terminals by GABA_B receptors indirectly activated by the PAD-evoked spike (GABA_B mediated presynaptic inhibition).