Thus, the mPFC is a prime candidate region for the relay of social memory-related signaling from the vHIP. Excitatory pyramidal neurons of the ventral hippocampus (vHIP) send long-range projections to the mPFC ( Dégenètais et al., 2003 Dembrow et al., 2010 Liu and Carter, 2018 Thierry et al., 2000), and the activity of different populations of mPFC pyramidal neurons are correlated with the novelty of a social target ( Liang et al., 2018). Altering the E/I balance in the medial prefrontal cortex (mPFC) of mice mimics autism-like social deficits ( Yizhar et al., 2011), and restoring the E/I balance in the CNTNAP2 knockout (KO) and valproate mouse models of ASDs improves their social deficits ( Brumback et al., 2018 Selimbeyoglu et al., 2017). A common feature in mouse models of monogenic ASDs is an imbalance in synaptic excitation and inhibition (E/I) within different brain regions ( Nelson and Valakh, 2015). However, debate remains as to which long-range efferent projections from the hippocampus are required for the formation of social memories.Īutism spectrum disorders (ASDs) are characterized by difficulties in interpreting social situations and a lack of social appropriation ( Barendse et al., 2018). In mouse models, perturbing neuronal activity in both dorsal CA2 and ventral CA1 hippocampal subregions impairs social memory ( Hitti and Siegelbaum, 2014 Meira et al., 2018 Okuyama et al., 2016). Functional neuroimaging in human subjects has revealed that higher covariance between hippocampal activity and changes in social environment reflect better social skills ( Tavares et al., 2015). Previous studies have identified the hippocampal network as the brain region that tracks social encounters in both human subjects and mouse models ( Hitti and Siegelbaum, 2014 Meira et al., 2018 Okuyama et al., 2016 Tavares et al., 2015).
HIPPOCAMPUS ANATOMY MOUSE UPDATE
A person or animal must reliably recall previous social interactions to make appropriate social responses and then update the memory with each new encounter. Social interactions are a fundamental part of our daily lives, and impairments in social cognition are key features of multiple neuropsychiatric illnesses. 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. 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. The extent of social memory improvement was negatively correlated with vHIP-evoked responses in mPFC slices, on a mouse-per-mouse basis. 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. 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. Inputs from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC) are implicated in several neuropsychiatric disorders.