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 parvalbuminexpressing, 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.gamma oscillations | synaptic transmission | Cre recombinase | dendrite | slice T yrosine kinase B receptor (TrkB), the cognate receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin-4, mediates key signaling events that control many aspects of neuronal development and function (1-4), including the maturation of parvalbumin-positive (PV+) interneurons in the hippocampal microcircuit. BDNF is preferentially synthesized in, and secreted from glutamatergic neurons, whereas trkB is expressed in both glutamatergic and γ-aminobutyric acid (GABA)-ergic neurons in hippocampus (5). Among cortical interneurons, PV+ interneurons express trkB abundantly (6). This anatomical organization of the BDNF signaling components and the known importance of feedback and feedforward communication between principal cells and interneurons (7-11) suggest a potential role for TrkB signaling in modulating neuronal network function.Rhythmic activity in cortical networks is important for the formation of neuronal assemblies (12)(13)(14). Of particular interest is rhythmic network activity in the gamma-frequency band (30-80 Hz, gamma oscillations) (15-17). Gamma oscillations are a result of the synchronized electrical activity of the neurons within a network and are thought to be important for temporal encoding, binding of sensory features, and memory storage and retrieval (18)(19)(20)(21)(22). Moreover, gamma oscillations are altered in several brain disorders, such as Alzheimer's disease (23-25), schizophrenia (24, 26-31), and epilepsy (24,32,33). Gamma oscillations are exquisitely susceptible to modulation of the cellular and synaptic mechanisms underlying the rhythmic activity. Fast-spiking PV+ interneurons are the main recipient of recurrent glutamatergic innervations in the hippocampal circuitry, and their role in gamma-frequency synchronization in cortical and hippocampal networks is well-establish...