Perirhinal cortex abnormalities impair hippocampal plasticity and learning in Scn2a, Fmr1, and Cdkl5 autism mouse models

Learning and memory deficits, including spatial navigation difficulties, are common in Autism Spectrum Disorder (ASD), yet the neurobiological underpinning of this phenotype remains unknown. Several ASD mouse models (Scn2a+/- , Fmr1-/-, Cdkl5-/-) exhibit impaired spatial learning, with these deficits often attributed to hippocampal dysfunction. However, we identify the perirhinal cortex (PRC) as a critical driver of these deficits. Cortical-wide Scn2a reduction in excitatory neurons replicated the spatial learning and long-term potentiation (LTP) impairments— a cellular correlate of learning—seen in Scn2a+/- mice, while hippocampal-wide reduction did not. PRC-specific viral-mediated Scn2a reduction in excitatory neurons decreased release probability, which consequently disrupted synaptic transmission and LTP in the hippocampus, as well as spatial learning. As PRC activity was reduced, chemogenetic activation of the PRC reversed these deficits in Scn2a+/- mice and rescued spatial learnin...,
Slice Preparation
 Using standard methods, horizontal brain sections (350 µM) containing hippocampus and perirhinal cortex were collected from mice aged postnatal day 21 (surgically naïve mice) to postnatal day 70 (mice which underwent viral injection and behavior testing). For slice preparation from surgically naïve mice, the cutting solution contained (in mM): 85 NaCl, 2.5 KCl, 1.25 NaH2PO4-H2O, 3 MgSO4·7H2O, 0.5 L-ascorbic acid, 0.5 CaCl2, 75 sucrose, 25 D-(+)-glucose, and 25 NaHCO3. For slice preparation from mice which underwent viral injection, the cutting solution contained (in mM): 2.5 KCl, 1.25 NaH2PO4-H2O, 0.4 L-ascorbic acid, 3 MgSO4·7H2O, 200 sucrose, 20 D-(+)-glucose, and 26 NaHCO3. Both solutions were neutral pH (i.e., 7.3), 310 mOsm, and saturated with 95% O2 and 5% CO2. Once cut, slices were transferred to an incubation chamber (Campden Instruments, Model 7470) filled with oxygenated artificial cerebrospinal fluid (ACSF) (Standard Ringer’s Solution, 300 mOsm, in mM: 119..., , # Perirhinal cortex abnormalities impair hippocampal plasticity and learning in Scn2a, Fmr1, and Cdkl5 autism mouse models

[https://doi.org/10.5061/dryad.6djh9w1c8](https://doi.org/10.5061/dryad.6djh9w1c8)

## Description of the data and file structure

The data from the electrophysiology experiments were uploaded as .txt files, each with specific data included as delineated by the title. Specifically, the means and standard error (SEM) for the input-output curves for each genotype, the raw values for fiber volley amplitude, the raw values for fEPSP slope (and amplitude, in the case of a few datasets), raw paired-pulse ratios (PPR) from fEPSP amplitude (a few genotypes, supplemental) or fEPSP slope, and LTP as determined by normalizing either the fEPSP amplitude (Amp) or the fEPSP slope (Slope) to baseline. The LTP data also includes 'timepoints' data, which is data that is averaged from 20 - 30 min (second row) and data averaged from 50 - 60 min (third row) compared to baseline (first...