Ventral hippocampal projections to the medial prefrontal cortex regulate social memory

• Published in: eLife Vol. 8
• Main Authors: Phillips, Mary L, Robinson, Holly Anne, Pozzo-Miller, Lucas
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 21.05.2019; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Autism; Autism Spectrum Disorder - metabolism; Autism Spectrum Disorder - pathology; Behavior; Behavior, Animal - physiology; Genotype & phenotype; Hippocampus; Hippocampus (Brain); Hippocampus - metabolism; Hippocampus - pathology; Human subjects; Humans; Innervation; Mecp2; MeCP2 protein; medial prefrontal cortex; Memory; Memory - physiology; Mental disorders; Methyl-CpG binding protein; Mice; Neurons; Neuroscience; Neurosciences; Physiological aspects; Prefrontal cortex; Prefrontal Cortex - metabolism; Prefrontal Cortex - pathology; Pyramidal cells; Pyramidal Cells - metabolism; Pyramidal Cells - pathology; Rett syndrome; Rett Syndrome - metabolism; Rett Syndrome - pathology; Rodents; social memory; Synaptic strength; Temporal Lobe - metabolism; Temporal Lobe - pathology; ventral hippocampus; United States; United States > US; Mecp2; mouse; medial prefrontal cortex; ventral hippocampus; neuroscience; Rett syndrome; autism; social memory
• DOI: 10.7554/eLife.44182
• ISSN: 2050-084X

Inputs from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC) are implicated in several neuropsychiatric disorders. Here, we show that the vHIP-mPFC projection is hyperactive in the Mecp2 knockout mouse model of the autism spectrum disorder Rett syndrome, which has deficits in social memory. Long-term excitation of mPFC-projecting vHIP neurons in wild-type mice impaired social memory, whereas their long-term inhibition in Rett mice rescued social memory deficits. The extent of social memory improvement was negatively correlated with vHIP-evoked responses in mPFC slices, on a mouse-per-mouse basis. Acute manipulations of the vHIP-mPFC projection affected social memory in a region and behavior selective manner, suggesting that proper vHIP-mPFC signaling is necessary to recall social memories. In addition, we identified an altered pattern of vHIP innervation of mPFC neurons, and increased synaptic strength of vHIP inputs onto layer five pyramidal neurons as contributing factors of aberrant vHIP-mPFC signaling in Rett mice.