Adult trkB signaling in parvalbumin interneurons is essential to prefrontal network dynamics
Author: Guyon, Nicolas; Zacharias, Leonardo Rakauskas; van Lunteren, Josina Anna; Immenschuh, Jana; Fuzik, Janos; Märtin, Antje; Xuan, Yang; Zilberter, Misha; Kim, Hoseok; Meletis, Konstantinos; Lopes-Aguiar, Cleiton; Carlén, Marie
Department: Inst för neurovetenskap / Dept of Neuroscience
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Abstract
Inhibitory interneurons expressing parvalbumin (PV) are central to cortical network dynamics, generation of c 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.
Institution:
- Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, Universidade de São Paulo, Ribeirão Preto, Brazil
- Center for Mathematics, Computing and Cognition- Universidade Federal do ABC, São Bernardo do Campo, Brazil
- Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York
- Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
Citation: J Neurosci. 2021 Apr 7;41(14):3120-3141
Citation DOI: 10.1523/JNEUROSCI.1848-20.2021
Citation PMID: 33593859
Citation ISI: 000637702000008
Publishing journal: Journal of Neuroscience
Eprint status: Peer Reviewed
Version: Published
Issue date: 2021-05-31
Sponsorship:
- STINT Program Joint Brazilian-Swedish Research Collaboration, BR2014-5869
- CAPES-STINT Program, 99999.009883/2014-02
- European Research Council, 337069
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)-Finance, 001
- São Paulo Research Foundation FAPESP, 2012/07107-2
- Knut and Alice Wallenberg Foundation, KAW 2012.0131
- Swedish Research Council, 2016-02700
- Karolinska Institutet, 2016-00139
Rights:
CC BY 4.0
Publication year: 2021
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