We have examined the molecular and cellular mechanisms that lead to the emergence of synchronous firing of CA1 pyramidal neurons in the developing rat hippocampus in response to high-frequency stimulation (HFS). The experiments were done on isolated CA1 pyramidal neurons (microfluorescence measurements of pH_i) and hippocampal slices (both electrophysiological and microfluorescence measurements). High-frequency stimulation in s. radiatum evoked synchronous gamma-frequency (20-80 Hz) firing only after postnatal day 12. This was attributable to an abrupt developmental upregulation of intrapyramidal carbonic anhydrase (CA). The data obtained show that intrapyramidal CA is a key molecule in the generation of HFS-induced non-synaptic GABAergic excitation which depends on the presence of CO₂/HCO₃ and is mediated by an increase in extracellular [K⁺]. These results point to a crucial role for the developmental expression of intrapyramidal carbonic anhydrase in shaping hippocampal integrative functions, long-term plasticity, and susceptibility to epileptogenesis. Further studies are needed to find out whether neuronal CA has a similar role in other brain areas in the control of large-scale population activity.

This work was supported by the Academy of Finland and the Sigrid Juselius Foundation.