Cell Type-Specific Effects of Adenosine on Cortical Neurons

The neuromodulator adenosine is widely considered to be a key regulator of sleep homeostasis and an indicator of sleep need. Although the effect of adenosine on subcortical areas has been previously described, the effects on cortical neurons have not been addressed systematically to date. To that purpose, we performed in vitro whole-cell patch-clamp recordings and biocytin staining of pyramidal neurons and interneurons throughout all layers of rat prefrontal and somatosensory cortex, followed by morphological analysis. We found that adenosine, via the A1 receptor, exerts differential effects depending on neuronal cell type and laminar location. Interneurons and pyramidal neurons in layer 2 and a subpopulation of layer 3 pyramidal neurons that displayed regular spiking were insensitive to adenosine application, whereas other pyramidal cells in layers 3-6 were hyperpolarized (range 1.2-10.8 mV). Broad tufted pyramidal neurons with little spike adaptation showed a small adenosine response, whereas slender tufted pyramidal neurons with substantial adaptation showed a bigger response. These studies of the action of adenosine at the postsynaptic level may contribute to the understanding of the changes in cortical circuit functioning that take place between sleep and awakening.