PMID- 28968898 OWN - NLM STAT- MEDLINE DCOM- 20191106 LR - 20191210 IS - 1460-2199 (Electronic) IS - 1047-3211 (Print) IS - 1047-3211 (Linking) VI - 28 IP - 10 DP - 2018 Oct 1 TI - Loss of TrkB Signaling in Parvalbumin-Expressing Basket Cells Results in Network Activity Disruption and Abnormal Behavior. PG - 3399-3413 LID - 10.1093/cercor/bhx173 [doi] AB - The GABAergic system is regulated by the brain-derived neurotrophic factor (BDNF)/Tropomyosin-related kinase B (TrkB) pathway, but the cell-intrinsic role of TrkB signaling in parvalbumin cortical interneuron development and function is unclear. We performed conditional ablation of the TrkB receptor in parvalbumin-expressing (PV) interneurons to study whether postnatal loss of TrkB in parvalbumin cells affects their survival, connectivity, spontaneous and evoked neuronal activity and behavior. Using in vivo recordings of local field potentials, we found reduced gamma oscillations in the sensory cortex of PVcre+; TrkBF/F conditional knockout mice (TrkB cKO), along with increased firing of putative excitatory neurons. There was a significant downregulation in parvalbumin neuron number in cerebral and cerebellar cortices of TrkB cKO mice. In addition, inhibitory synaptic connections between basket cells and pyramidal neurons were profoundly reduced in the neocortex of TrkB cKO mice and there was a loss of cortical volume. TrkB cKO mice also showed profound hyperactivity, stereotypies, motor deficits and learning/memory defects. Our findings demonstrate that the targeting and/or synapse formation of PV-expressing basket cells with principal excitatory neurons require TrkB signaling in parvalbumin cells. Disruption of this signaling has major consequences for parvalbumin interneuron connectivity, network dynamics, cognitive and motor behavior. FAU - Xenos, Dionysios AU - Xenos D AD - Child Study Center. FAU - Kamceva, Marija AU - Kamceva M AD - Child Study Center. FAU - Tomasi, Simone AU - Tomasi S AD - Child Study Center. FAU - Cardin, Jessica A AU - Cardin JA AD - Department of Neuroscience. AD - Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, USA. FAU - Schwartz, Michael L AU - Schwartz ML AD - Department of Neuroscience. FAU - Vaccarino, Flora M AU - Vaccarino FM AD - Child Study Center. AD - Department of Neuroscience. AD - Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, USA. LA - eng GR - R01 EY022951/EY/NEI NIH HHS/United States GR - P01 NS062686/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Cereb Cortex JT - Cerebral cortex (New York, N.Y. : 1991) JID - 9110718 RN - 0 (Membrane Glycoproteins) RN - 0 (Parvalbumins) RN - EC 2.7.10.1 (Ntrk2 protein, mouse) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM MH - Animals MH - *Behavior, Animal MH - Cerebral Cortex/*cytology/*physiopathology MH - Electrophysiological Phenomena/genetics MH - Evoked Potentials/physiology MH - *Interneurons MH - Learning Disabilities/genetics/psychology MH - Membrane Glycoproteins/deficiency/*genetics MH - Memory Disorders/genetics/psychology MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Movement Disorders/genetics/psychology MH - Neocortex/cytology MH - *Neurons MH - Parvalbumins/biosynthesis/genetics MH - Protein-Tyrosine Kinases/deficiency/*genetics MH - Pyramidal Cells MH - Survival Analysis PMC - PMC6132287 EDAT- 2017/10/03 06:00 MHDA- 2019/11/07 06:00 PMCR- 2019/10/01 CRDT- 2017/10/03 06:00 PHST- 2016/06/17 00:00 [received] PHST- 2017/10/03 06:00 [pubmed] PHST- 2019/11/07 06:00 [medline] PHST- 2017/10/03 06:00 [entrez] PHST- 2019/10/01 00:00 [pmc-release] AID - 4084668 [pii] AID - bhx173 [pii] AID - 10.1093/cercor/bhx173 [doi] PST - ppublish SO - Cereb Cortex. 2018 Oct 1;28(10):3399-3413. doi: 10.1093/cercor/bhx173.