This unit is designed to provide sufficient instruction for the setup and execution of tests for object location and object recognition in adult mice. This task is ideally suited for the study of a variety of mouse models that examine disease mechanisms and novel therapeutic targets. By altering several key parameters, the experimenter can investigate short‐term or long‐term memory and look for either memory impairments or enhancements. Object location and object recognition memory tasks rely on a rodent's innate preference for novelty, and can be conducted sequentially in the same cohort of animals. These two tasks avoid the inherent stress induced with other common measures of rodent memory such as fear conditioning and the Morris water maze. This protocol covers detailed instructions on conducting both tasks, as well as key points concerning data collection, analysis, and interpretation. Curr. Protoc. Neurosci. 69:8.31.1‐8.31.17. © 2014 by John Wiley & Sons, Inc.

BAF53b is a neuron-specific component of the nucleosome remodeling complex mSWI/SNF that allows euchromatin formation and provides epigenetic regulation of gene expression. Here, the authors generated BAF53b mutant and rescue mice to show that postnatal nucleosome modeling is crucial to hippocampal synaptic plasticity, neuronal morphology and memory performance. Recent exome sequencing studies have implicated polymorphic Brg1-Associated Factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several human intellectual disabilities and cognitive disorders. However, it is currently unknown how mutations in BAF complexes result in impaired cognitive function. Postmitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Mice harboring selective genetic manipulations of BAF53b have severe defects in long-term memory and long-lasting forms of hippocampal synaptic plasticity. We rescued memory impairments in BAF53b mutant mice by reintroducing BAF53b in the adult hippocampus, which suggests a role for BAF53b beyond neuronal development. The defects in BAF53b mutant mice appeared to derive from alterations in gene expression that produce abnormal postsynaptic components, such as spine structure and function, and ultimately lead to deficits in synaptic plasticity. Our results provide new insight into the role of dominant mutations in subunits of BAF complexes in human intellectual and cognitive disorders.

Aging is accompanied by impairments in both circadian rhythmicity and long-term memory. Although it is clear that memory performance is affected by circadian cycling, it is unknown whether age-related disruption of the circadian clock causes impaired hippocampal memory. Here, we show that the repressive histone deacetylase HDAC3 restricts long-term memory, synaptic plasticity, and experience-induced expression of the circadian genePer1in the aging hippocampus without affecting rhythmic circadian activity patterns. We also demonstrate that hippocampalPer1is critical for long-term memory formation. Together, our data challenge the traditional idea that alterations in the core circadian clock drive circadian-related changes in memory formation and instead argue for a more autonomous role for circadian clock gene function in hippocampal cells to gate the likelihood of long-term memory formation.

Significance: Transcriptional dysregulation is an early and reproducible feature of Huntington disease (HD); however, mechanisms underlying this dysregulation are unclear. This article describes a unique pattern of the chromatin mark H3K4me3 at transcriptionally repressed promoters in HD mouse and human brain identified by genome-wide analysis. Reducing the levels of the demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin expression and was neuroprotective in a Drosophila HD model. These results suggest that targeting epigenetic signatures may be an effective strategy to ameliorate the consequences of HD and other neurodegenerative diseases.