Somatodendritic integration under increased network activity in layer 5 pyramidal cells of the somatosensory cortex.

Integrative properties of single neurons have been extensively studied in acute brain slices. However, these preparations are characterized by extremely low levels of synaptic and action potential activity. In comparison to in vivo, reduced intracortical input and lack of subcortical modulation increase the effective difference between mean membrane potential and spiking threshold, preventing self-sustained network activity in vitro. To elicit an increased and stable network activity (INA) in vitro comparable to that found in awake animals, we mimicked subcortical cholinergic and serotoninergic inputs using carbachol or barium alone or in combination with serotonin in layer 5 pyramidal cells in slices of mouse somatosensory cortex. INA is primarily induced by a modulation of intrinsic conductances resulting in a depolarization of the membrane potential. We studied the impact of INA on synaptic and somatodendritic integration using extracellular stimulation and dendritic calcium imaging. Synaptic inhibition is strengthened due to an increased driving force for chloride. The critical frequency at which somatic action potentials induce a dendritic calcium action potential is lowered. Simultaneous inhibitory synaptic input is powerful enough to suppress dendritic calcium action potential generation. Pharmacologically induced INA enables the study of neuronal integration in well-accessible cortical slices within an active network.