Carbonic Anhydrase Isoform VII Acts as a Molecular Switch in the Development of Synchronous Gamma-Frequency Firing of Hippocampal CA1 Pyramidal Cells

Abstract

Identification of the molecular mechanisms that enable synchronous firing of CA1 pyramidal neurons is central to the understanding of the functional properties of this major hippocampal output pathway. Using microfluorescence measurements of intraneuronal pH, in situ hybridization, as well as intracellular, extracellular, and K ϩ -sensitive microelectrode recordings, we show now that the capability for synchronous gamma-frequency (20 -80 Hz) firing in response to high-frequency stimulation (HFS) emerges abruptly in the rat hippocampus at approximately postnatal day 12. This was attributable to a steep developmental upregulation of intrapyramidal carbonic anhydrase isoform VII, which acts as a key molecule in the generation of HFS-induced tonic GABAergic excitation. These results point to a crucial role for the developmental expression of intrapyramidal carbonic anhydrase VII activity in shaping integrative functions, long-term plasticity and susceptibility to epileptogenesis.

Carbonic anhydrase VII–a potential prognostic marker in gliomas

“…Although studies on CA II and CA XII have been mainly focused on normal tissues, there are a few previous reports, showing their presence in cancer cells and especially in brain tumors where they have shown significant association with prognosis [6,7,25]. CA VII is a cytosolic isozyme which was first demonstrated in the brain tissue [35], where it has been linked to the regulation of GABAergic neuronal transmission in hippocampal neurons [36]. We recently characterized this enzyme in vitro and identified two forms of CA VII mRNA in the human brain [21].…”

Spontaneous Network Events Driven by Depolarizing GABA Action in Neonatal Hippocampal Slices are Not Attributable to Deficient Mitochondrial Energy Metabolism

“…Slices were perfused at 2.5 ml/min (chamber volume, 1.5 ml). BCECF-AM (10 M; Invitrogen) was injected into the CA3c-b area via patch pipette and the fluorescent signal was measured and calibrated as before (Ruusuvuori et al, 2004). After loading, slices were left to recover for 20 -30 min before recordings from the somatic region of CA3 pyramidal neurons were started.…”

A Single Seizure Episode Leads to Rapid Functional Activation of KCC2 in the Neonatal Rat Hippocampus

“…In some experiments with K252a, field potential activity was quantified within two frequency bands (4 -25 Hz and 25-100 Hz) by calculating the cumulative rootmean square (RMS) of the extracellular signal for a 30 min epoch (cf. Ruusuvuori et al, 2004).…”