Neuronal activation affects the organization and protein composition of the nuclear speckles.

Nuclear speckles, also known as interchromatin granule clusters (IGCs), are subnuclear domains highly enriched in proteins involved in transcription and mRNA metabolism and, until recently, have been regarded primarily as their storage and modification hubs. However, several recent studies on non-neuronal cell types indicate that nuclear speckles may directly contribute to gene expression as some of the active genes have been shown to associate with these structures. Neuronal activity is one of the key transcriptional regulators and may lead to the rearrangement of some nuclear bodies. Notably, the impact of neuronal activation on IGC/nuclear speckles organization and function remains unexplored. To address this research gap, we examined whether and how neuronal stimulation affects the organization of these bodies in granular neurons from the rat hippocampal formation. Our findings demonstrate that neuronal stimulation induces morphological and proteomic remodelling of the nuclear speckles under both in vitro and in vivo conditions. Importantly, these changes are not associated with cellular stress or cell death but are dependent on transcription and splicing.

Activation-induced chromatin reorganization in neurons depends on HDAC1 activity.

Spatial chromatin organization is crucial for transcriptional regulation and might be particularly important in neurons since they dramatically change their transcriptome in response to external stimuli. We show that stimulation of neurons causes condensation of large chromatin domains. This phenomenon can be observed in vitro in cultured rat hippocampal neurons as well as in vivo in the amygdala and hippocampal neurons. Activity-induced chromatin condensation is an active, rapid, energy-dependent, and reversible process. It involves calcium-dependent pathways but is independent of active transcription. It is accompanied by the redistribution of posttranslational histone modifications and rearrangements in the spatial organization of chromosome territories. Moreover, it leads to the reorganization of nuclear speckles and active domains located in their proximity. Finally, we find that the histone deacetylase HDAC1 is the key regulator of this process. Our results suggest that HDAC1-dependent chromatin reorganization constitutes an important level of transcriptional regulation in neurons.