Adult trkB Signaling in Parvalbumin Interneurons is Essential to Prefrontal Network Dynamics

Author(s):Show less -

Guyon, Nicolas ^[1] ; Zacharias, Leonardo Rakauskas ^[2] ; van Lunteren, Josina Anna ^[3] ; Immenschuh, Jana ^[1] ; Fuzik, Janos ^[1] ; Martin, Antje ^[1] ; Xuan, Yang ^[1] ; Zilberter, Misha ^[1] ; Kim, Hoseok ^[1] ; Meletis, Konstantinos ^[1] ; Lopes-Aguiar, Cleiton ^[4] ; Carlen, Marie ^{[1, 3]}

Affiliation

^[1] Karolinska Inst, Dept Neurosci, S-17177 Stockholm - Sweden

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav Sci, BR-14049900 Ribeirao Preto - Brazil

^[3] Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge - Sweden

^[4] Univ Fed Minas Gerais, Inst Biol Sci, Dept Physiol & Biophys, BR-31270901 Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: JOURNAL OF NEUROSCIENCE; v. 41, n. 14, p. 3120-3141, APR 7 2021.
• Web of Science Citations: 3

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. (AU)

• FAPESP's process: 12/07107-2 - Episodic-like memory and oscillatory patterns in the hippocampus and medial prefrontal cortex of adult rats subjected to early-life seizures
• Grantee: Cleiton Lopes Aguiar
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate