Standardized Electrophysiological Approaches for CA1 Field Recordings:
Insights into the AS Mouse Model
Melinda M Peters, Joseph E. Pick and Edwin J. Weeber
Published November 1, 2025
https://doi.org/10.65856/JJBD6749
KEYWORDS: Long-term potentiation, hippocampus, high frequency stimulation, animal models, synapse, synaptic function, synaptic plasticity.
ABSTRACT: The hippocampal CA3/CA1 Schaffer collateral pathway provides a lamina-resolved and highly reproducible synaptic pathway for quantifying synaptic transmission and plasticity in acute rodent brain slices. This paper consolidates best practices for CA1 field electrophysiology and links them to disease-relevant readouts in Angelman syndrome (AS) models. We detail a rigorously controlled pipeline spanning sucrose-based, low-Ca²⁺/high-Mg²⁺ cutting solutions; staged recovery from ice-cold to warmed (30–32 °C) artificial cerebrospinal fluid (ACSF); strict management of bicarbonate buffering to prevent divalent precipitation; and recording parameters that yield clean, minimally filtered field excitatory post-synaptic potentials (EPSPs). Quantification emphasizes the initial field excitatory post-synaptic potential (fEPSP) slope measured within a fixed, pre-registered window, normalization to a stable baseline, and exclusion criteria that guard against artifacts. We outline how input–output curves, establish basal synaptic gain and the operating point for plasticity assays, and we compare induction paradigms-consisting of classical 100 Hz high frequency stimulation (HFS), theta-frequency and theta-burst stimulation, and ultra-high-frequency stimulation. Applying this framework to AS mouse and rat models, we summarize how electrophysiology discriminates a shifted induction threshold from a true capacity deficit requiring restoration of downstream expression mechanisms or Ube3a function. The approach delivers a mechanistically interpretable, quantitative biomarker for AS that is suitable for preclinical screening and for testing gene-targeted and synaptic-level therapies. Collectively, these standardized practices, spanning anatomy, solutions, data acquisition, and analysis, establish a reproducible framework and a translational lens for interpreting hippocampal LTP in AS and other neurodevelopmental disease models.