Related Experiment Video
Updated: Jun 22, 2026
07:44
Evaluation of Synapse Density in Hippocampal Rodent Brain Slices
Published on: October 6, 2017
Histone deacetylases 1 and 2 form a developmental switch that controls excitatory synapse maturation and function
Mohd W Akhtar1, Jesica Raingo, Erika D Nelson
1Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA.
Summary
Histone deacetylases (HDACs), specifically HDAC1 and HDAC2, control synapse maturation. Inhibiting these enzymes accelerates excitatory synapse development and function in the brain.
Area of Science:
- Neuroscience
- Molecular Biology
- Epigenetics
Background:
- Synapse formation is rapid, but maturation is delayed, hindering functionality.
- Mechanisms underlying delayed synapse maturation remain unclear.
- Histone deacetylases (HDACs) regulate gene expression epigenetically; Class I HDACs (HDAC1, HDAC2) are in the CNS but their neuronal roles are unstudied.
Purpose of the Study:
- To investigate the role of HDAC1 and HDAC2 in neuronal development and synapse maturation.
- To determine how HDAC activity influences excitatory synapse formation and function.
Main Methods:
- Utilized pharmacological HDAC inhibitors.
- Employed mice with conditional alleles for HDAC1 and HDAC2.
- Assessed synapse maturation, number, and neurotransmission.
Main Results:
- Decreased HDAC1 and HDAC2 activity during early development facilitated excitatory synapse maturation and increased synapse numbers.
- In mature neurons, reduced HDAC2 alone attenuated basal excitatory neurotransmission without altering nerve terminal numbers.
Conclusions:
- HDAC1 and HDAC2 act as a developmental switch controlling synapse maturation and function.
- Their role is dependent on the maturational state of neuronal networks.
Related Concept Videos
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
01:29Excitatory and Inhibitory Effects of Neurotransmitters
When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of specific...
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...