Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In Vivo

The excitability of the apical tuft of layer 5 pyramidal neurons is thought to play a crucial role in behavioral performance and synaptic plasticity. We show that the excitability of the apical tuft is sensitive to adrenergic neuromodulation. Using two-photon dendritic Ca²⁺ imaging and in vivo whole-cell and extracellular recordings in awake mice, we show that application of the α2A-adrenoceptor agonist guanfacine increases the probability of dendritic Ca²⁺ events in the tuft and lowers the threshold for dendritic Ca²⁺ spikes. We further show that these effects are likely to be mediated by the dendritic current I_h. Modulation of I_h in a realistic compartmental model controlled both the generation and magnitude of dendritic calcium spikes in the apical tuft. These findings suggest that adrenergic neuromodulation may affect cognitive processes such as sensory integration, attention, and working memory by regulating the sensitivity of layer 5 pyramidal neurons to top-down inputs.