Nov 4, 2018

Ventral hippocampal projections to the medial prefrontal cortex regulate social memory

BioRxiv : the Preprint Server for Biology
Mary L PhillipsLucas Pozzo-Miller

Abstract

Inputs from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC) have been implicated in several neuropsychiatric disorders. Here, we show that the long-range vHIP-mPFC projection is hyperactive in the Mecp2 knockout (KO) mouse model of the autism spectrum disorder Rett syndrome, which has deficits in social memory. Chronically mimicking vHIP-mPFC hyperexcitability in wild-type mice impaired social memory, whereas chronic inhibition of mPFC-projecting vHIP neurons in Mecp2 KO mice rescued social memory deficits; the extent of memory rescue was negatively correlated with the strength of vHIP input to the mPFC. Acute manipulations of the vHIP-mPFC projection also affected social memory in a specific and selective manner, suggesting that proper vHIP-mPFC signaling is necessary to recall social memories. In addition, we identified an altered vHIP-mPFC innervation pattern and increased synaptic strength onto layer 5 pyramidal neurons as contributing factors in aberrant vHIP-mPFC signaling in Mecp2 KO mice.

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Mentioned in this Paper

MECP2 wt Allele
Projections and Predictions
Methyl-CpG-Binding Protein 2
Regulation of Biological Process
Muscle Innervation, Function
Memory Impairment
Neurons
Knock-out
Nerve Supply
MECP2 gene

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