Brain-wide screen of prelimbic cortex inputs reveals a functional shift during early fear memory consolidation.

Memory formation and storage rely on multiple interconnected brain areas, the contribution of which varies during memory consolidation. The medial prefrontal cortex, in particular the prelimbic cortex (PL), was traditionally found to be involved in remote memory storage, but recent evidence points toward its implication in early consolidation as well. Nevertheless, the inputs to the PL governing these dynamics remain unknown.

The Medial Prefrontal Cortex and Fear Memory: Dynamics, Connectivity, and Engrams.

It is becoming increasingly apparent that long-term memory formation relies on a distributed network of brain areas. While the hippocampus has been at the center of attention for decades, it is now clear that other regions, in particular the medial prefrontal cortex (mPFC), are taking an active part as well. Recent evidence suggests that the mPFC-traditionally implicated in the long-term storage of memories-is already critical for the early phases of memory formation such as encoding.

Reactivation of recall-induced neurons contributes to remote fear memory attenuation.

Whether fear attenuation is mediated by inhibition of the original memory trace of fear with a new memory trace of safety or by updating of the original fear trace toward safety has been a long-standing question in neuroscience and psychology alike. In particular, which of the two scenarios underlies the attenuation of remote (month-old) fear memories is completely unknown, despite the impetus to better understand this process against the backdrop of enduring traumata. We found-chemogenetically and in an engram-specific manner-that effective remote fear attenuation is accompanied by the reactivation of memory recall-induced neurons in the dentate gyrus and that the continued activity of these neurons is critical for fear reduction.

PM20D1 is a quantitative trait locus associated with Alzheimer's disease.

The chances to develop Alzheimer's disease (AD) result from a combination of genetic and non-genetic risk factors , the latter likely being mediated by epigenetic mechanisms . In the past, genome-wide association studies (GWAS) have identified an important number of risk loci associated with AD pathology , but a causal relationship remains difficult to establish. In contrast, locus-specific or epigenome-wide association studies (EWAS) have revealed site-specific epigenetic alterations, which provide mechanistic insights for a particular risk gene but often lack the statistical power of GWAS .