HDAC1 negatively regulates Bdnf and Pvalb required for parvalbumin interneuron maturation in an experience‐dependent manner

• Published in: Journal of neurochemistry Vol. 139; no. 3; pp. 369 - 380
• Main Authors: Koh, Dawn X. P., Sng, Judy C. G.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2016
• Subjects: Animals; Animals, Newborn; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Chromatin; deprivation; development; Epigenesis, Genetic - physiology; Epigenetics; Gene expression; Histone Deacetylase 1 - deficiency; Histone Deacetylase 1 - genetics; Histone Deacetylase 1 - metabolism; inhibitory; Interneurons - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Pathways - growth & development; Neurochemistry; Parvalbumins - genetics; Parvalbumins - metabolism; Parvalbumins - physiology; Pyramidal Cells - metabolism; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Sensation; Sensory Deprivation; somatosensory; Somatosensory Cortex - growth & development; Somatosensory Cortex - physiology; Vibrissae - innervation; Vibrissae - physiology; whisker; deprivation; somatosensory; development; whisker; epigenetics; inhibitory
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.13773

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. We proposed that whisker deprivation causes changes in the epigenome altering excitatory/inhibitory balance in the primary somatosensory cortex S1. We demonstrated increased histone deacetylase HDAC1 activity and expression with whisker deprivation, accompanied by increased HDAC1 and HDAC2 association at Bdnf (brain‐derived neurotrophic factor) and Pvalb (parvalbumin) resulting in decreased histone acetylation and gene transcription. Our findings provide new insight on experience‐dependent epigenetic mechanisms during brain development.