PT - JOURNAL ARTICLE AU - Eagle, Andrew L. AU - Williams, Elizabeth S. AU - Beatty, Joseph A. AU - Cox, Charles L. AU - Robison, Alfred J. TI - ΔFosB Decreases Excitability of Dorsal Hippocampal CA1 Neurons AID - 10.1523/ENEURO.0104-18.2018 DP - 2018 Jul 01 TA - eneuro PG - ENEURO.0104-18.2018 VI - 5 IP - 4 4099 - http://www.eneuro.org/content/5/4/ENEURO.0104-18.2018.short 4100 - http://www.eneuro.org/content/5/4/ENEURO.0104-18.2018.full SO - eNeuro2018 Jul 01; 5 AB - Both the function of hippocampal neurons and hippocampus-dependent behaviors are dependent on changes in gene expression, but the specific mechanisms that regulate gene expression in hippocampus are not yet fully understood. The stable, activity-dependent transcription factor ΔFosB plays a role in various forms of hippocampal-dependent learning and in the structural plasticity of synapses onto CA1 neurons. The authors examined the consequences of viral-mediated overexpression or inhibition of ΔFosB on the function of adult mouse hippocampal CA1 neurons using ex vivo slice whole-cell physiology. We found that the overexpression of ΔFosB decreased the excitability of CA1 pyramidal neurons, while inhibition increased excitability. Interestingly, these manipulations did not affect resting membrane potential or spike frequency adaptation, but ΔFosB overexpression reduced hyperpolarization-activated current. Both ΔFosB overexpression and inhibition decreased spontaneous excitatory postsynaptic currents, while only ΔFosB inhibition affected the AMPA/NMDA ratio, which was mediated by decreased NMDA receptor current, suggesting complex effects on synaptic inputs to CA1 that may be driven by homeostatic cell-autonomous or network-driven adaptations to the changes in CA1 cell excitability. Because ΔFosB is induced in hippocampus by drugs of abuse, stress, or antidepressant treatment, these results suggest that ΔFosB-driven changes in hippocampal cell excitability may be critical for learning and, in maladaptive states, are key drivers of aberrant hippocampal function in diseases such as addiction and depression.