Nociceptive Processing by Anterior Cingulate Pyramidal Neurons Revealed with Postsynaptic Responses

Authors

Bai-Chuang Shyu, Robert Walton Sikes, Leslie Joan Vogt, and Brent Alan Vogt

Abstract

Although cingulate cortex is frequently activated in acute human pain studies, postsynaptic responses are not known nor are links between nociceptive afferents, neuronal responses and outputs to other structures. Intracellular potentials were recorded from neurobiotin-injected, pyramidal neurons in anterior cingulate area 24b following noxious stimulation of the sciatic nerve in anesthetized rabbits. Layer IIIc pyramids had extensive and horizontally oriented basal dendrites in layer IIIc where nociceptive afferents terminate. They had the longest EPSPs (545 ms) that were modulated with hyperpolarizing currents. Pyramids in layer V had an intermediate tuft of oblique apical dendrites in layer IIIc that were 150-350 μm from somata in Va and 351-550 μm in Vb. Although average EPSP durations were short in layers II-IIIab (222±31), Va (267±65) and layer Vb (159±31), there were 5 neurons in layers IIIab-Va that had EPSP durations lasting more than 300 ms (548±63 ms). Neurons in layers IIIc, Va, and Vb had the highest amplitude EPSPs (6.25 mV, 6.84±0.58 mV, 6.4±0.47 mV, respectively), while those in layers II-IIIab were 5±0.56 mV. Nociceptive responses in layer Vb were complex and some had initial IPSPs with shorter duration EPSPs. Layers II-IIIab had dye-coupled pyramids and EPSPs in these layers had short-durations (167±33 ms) compared to IIIc-Va (487±28 ms) and this is the first report of dye-coupled pyramids. Thus, there are two populations of ACC pyramids with EPSPs of significantly different durations, but their dendritic morphologies do not predict EPSP duration. Short-duration EPSPs are thalamic-mediated, nociceptive responses lasting ≤200 ms. Longer, "integrative" EPSPs are >350 ms and are likely modulated by intracortical axon collateral discharges. These findings suggest that links between nociception and projections to cortical and motor systems are instantaneous because nociceptive responses are generated directly by pyramidal projection neurons in all layers.