TrkB signaling in parvalbumin-positive interneurons is critical for gamma-band network synchronization in hippocampus.

Abstract

Although brain-derived neurotrophic factor (BDNF) is known to regulate circuit development and synaptic plasticity, its exact role in neuronal network activity remains elusive. Using mutant mice (TrkB-PV(-/-)) in which the gene for the BDNF receptor, tyrosine kinase B receptor (trkB), has been specifically deleted in parvalbumin-expressing, fast-spiking GABAergic (PV+) interneurons, we show that TrkB is structurally and functionally important for the integrity of the hippocampal network. The amplitude of glutamatergic inputs to PV+ interneurons and the frequency of GABAergic inputs to excitatory pyramidal cells were reduced in the TrkB-PV(-/-) mice. Functionally, rhythmic network activity in the gamma-frequency band (30-80 Hz) was significantly decreased in hippocampal area CA1. This decrease was caused by a desynchronization and overall reduction in frequency of action potentials generated in PV+ interneurons of TrkB-PV(-/-) mice. Our results show that the integration of PV+ interneurons into the hippocampal microcircuit is impaired in TrkB-PV(-/-) mice, resulting in decreased rhythmic network activity in the gamma-frequency band.