期刊
JOURNAL OF NEUROSCIENCE
卷 41, 期 14, 页码 3120-3141出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1848-20.2021
关键词
cortical inhibition; dominant-negative receptor; gamma oscillations; medial prefrontal cortex; neurotrophins; social behavior
资金
- STINT Program Joint Brazilian-Swedish Research Collaboration grant [BR2014-5869]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES)-STINT Program Grant [99999.009883/2014-02]
- European Research Council Starting Grant [337069]
- CAPES [001]
- Wallenberg Academy Fellow in Medicine Grant from the Knut and Alice Wallenberg Foundation [KAW 2012.0131]
- Swedish Research Council [2016-02700]
- Karolinska Institutet Grant [2016-00139]
- Sao Paulo Research Foundation (FAPESP) Grant [2012/07107-2]
- Karolinska Institutet (KID funding)
- Karolinska Institutet
- European Research Council (ERC) [337069] Funding Source: European Research Council (ERC)
- Swedish Research Council [2016-02700] Funding Source: Swedish Research Council
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [12/07107-2] Funding Source: FAPESP
The BDNF/trkB signaling in prefrontal PV interneurons is essential to the integrity and maintenance of these interneurons in adult mice, leading to decreased PV inhibition and increased baseline local field potential activity.
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.
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