Figure 12

Schematic diagram summarising synaptic connections involving inhibitory calretinin cells and primary afferents. A non-peptidergic nociceptor (NP) forms excitatory synapses onto an inhibitory calretinin cell (iCR) in lamina II and a lamina I projection neuron belonging to the anterolateral system (ALS). The ALS cell is shown as representative of spinal neurons that are innervated by NP afferents. The iCR axon contributes to a synaptic triad, which is shown in more detail in the inset. The excitatory (glutamatergic) synapse between the NP afferent and the ALS cell is indicated with a yellow arrow. The axon of the iCR is presynaptic to the NP afferent (upper red arrow) at an axoaxonic synapse, and to the ALS cell dendrite (lower red arrow) at an axodendritic synapse. These synapses are both GABAergic, and mediate pre- and postsynaptic inhibition, respectively. GABA acting at the axoaxonic synapse will reduce glutamate release at the synapse from the NP afferent to the ALS cell (feedback inhibition), while at the axodendritic synapse it will directly inhibit the ALS cell (feedforward inhibition).