title: HDAC1 negatively regulates Bdnf and Pvalb required for parvalbumin interneuron maturation in an experience-dependent manner.
abstract: During early postnatal development, neuronal circuits are sculpted by sensory experience provided by the external environment. This experience-dependent regulation of circuitry development consolidates the balance of excitatory-inhibitory (E/I) neurons in the brain. The cortical barrel-column that innervates a single principal whisker is used to provide a clear reference frame for studying the consolidation of E/I circuitry. Sensory deprivation of S1 at birth disrupts the consolidation of excitatory-inhibitory balance by decreasing inhibitory transmission of parvalbumin interneurons. The molecular mechanisms underlying this decrease in inhibition are not completely understood. Our findings show that epigenetic mechanisms, in particular histone deacetylation by histone deacetylases, negatively regulate the expression of brain-derived neurotrophic factor (Bdnf) and parvalbumin (Pvalb) genes during development, which are required for the maturation of parvalbumin interneurons. After whisker deprivation, increased histone deacetylase 1 expression and activity led to increased histone deacetylase 1 binding and decreased histone acetylation at Bdnf promoters I-IV and Pvalb promoter, resulting in the repression of Bdnf and Pvalb gene transcription. The decrease in Bdnf expression further affected parvalbumin interneuron maturation at layer II/III in S1, demonstrated by decreased parvalbumin expression, a marker for parvalbumin interneuron maturation. Knockdown of HDAC1 recovered Bdnf and Pvalb gene transcription and also prevented the decrease of inhibitory synapses accompanying whisker deprivation.
authors.affiliation: National University of Singapore, Graduate School of Integrative Sciences and Engineering, Singapore, Singapore.|Singapore Institute of Clinical Sciences (SICS), A*STAR, Brenner Centre for Molecular Medicine, Singapore, Singapore.|Department of Pharmacology, National University of Singapore, Yong Loo Lin School of Medicine, Singapore, Singapore.
authors.forename: Dawn X P
authors.initials: DX
authors.lastname: Koh
authors.affiliation: Singapore Institute of Clinical Sciences (SICS), A*STAR, Brenner Centre for Molecular Medicine, Singapore, Singapore. phcsngj@nus.edu.sg.|Department of Pharmacology, National University of Singapore, Yong Loo Lin School of Medicine, Singapore, Singapore. phcsngj@nus.edu.sg.
authors.forename: Judy C G
authors.identifier: 0000-0002-6740-6940
authors.initials: JC
authors.lastname: Sng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology; D056284:Histone Deacetylase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000254:growth & development; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012677:Sensation; D012683:Sensory Deprivation; D013003:Somatosensory Cortex / Q000254:growth & development / Q000502:physiology; D014738:Vibrissae / Q000294:innervation / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D010320:Parvalbumins; D012333:RNA, Messenger; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1
keywords: deprivation; development; epigenetics; inhibitory; somatosensory; whisker