Adult trkB Signaling in Parvalbumin Interneurons is Essential to Prefrontal Network Dynamics
Open Access
- 16 February 2021
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 41 (14), 3120-3141
- https://doi.org/10.1523/jneurosci.1848-20.2021
Abstract
Inhibitory interneurons expressing parvalbumin (PV) are central to cortical network dynamics, generation of gamma oscillations, and cognition. Dysfunction of PV interneurons disrupts cortical information processing and cognitive behavior. Brain-derived neurotrophic factor (BDNF)/Tyrosine receptor kinase B (trkB) signaling regulates the maturation of cortical PV interneurons but is also implicated in their adult multidimensional functions. Using a novel viral strategy for cell-type-specific and spatially restricted expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance of prefrontal PV interneurons in adult male and female mice. Reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) resulted in deficient PV inhibition and increased baseline local field potential (LFP) activity in a broad frequency band. The altered network activity was particularly pronounced during increased activation of the prefrontal network and was associated with changed dynamics of local excitatory neurons, as well as decreased modulation of the LFP - abnormalities that appeared to generalize across stimuli and brain states. In addition, our findings link reduced BDNF/trkB signaling in prefrontal PV interneurons to increased aggression. Together our investigations demonstrate that BDNF/trkB signaling in PV interneurons in the adult mPFC is essential to local network dynamics and cognitive behavior. Our data provide direct support for the suggested association between decreased trkB signaling, deficient PV inhibition, and altered prefrontal circuitry. SIGNIFICANCE STATEMENT BDNF/trkB signaling promotes the maturation of inhibitory PV interneurons - neurons central to local cortical dynamics, gamma rhythms, and cognition. Here, we used a novel viral approach for reduced BDNF/trkB signaling in PV interneurons in the mPFC to establish the role of BDNF/trkB signaling in adult prefrontal network activities. Reduced BDNF/trkB signaling caused pronounced morphological alterations, reduced PV inhibition, and deficient prefrontal network dynamics. The altered network activity appeared to manifest across stimuli and brain states and was associated with aberrant LFP activities and increased aggression. The results demonstrate that adult BDNF/trkB signaling is essential to PV inhibition and prefrontal circuit function and directly links BDNF/trkB signaling to network integrity in the adult brain.Funding Information
- Knut och Alice Wallenbergs Stiftelse (KAW 2012.0131)
- Vetenskapsrådet (2016-02700)
- Karolinska Institutet (2016-00139)
- Swedish Foundation for International Cooperation in Research and Higher Education
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (99999.009883/2014-02)
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2012/07107-2)
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