ΔFosB Decreases Excitability of Dorsal Hippocampal CA1 Neurons

Abstract

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.

Circuit-specific hippocampal ΔFosB underlies resilience to stress-induced social avoidance

“…Moreover, ΔFosB decreased amplitude and increased half-width of evoked action potentials and decreased the frequency of spontaneous synaptic currents ( Fig. S10c-f), similar to what we have previously observed in dHPC CA1 neurons 18 . This suite of observations suggests that ΔFosB expression reduces the excitability of vHPC neurons, likely via changes in intrinsic membrane properties.…”

“…Because the excitability of afferent projections from vHPC CA1 extending to NAc mediate CSDS susceptibility 4 and ΔFosB regulates excitability of dHPC CA1 neurons 18 , we set out to investigate the role of vHPC projection neuron ΔFosB in CSDS susceptibility to social avoidance. To label vHPC-NAc neurons, we utilized a mouse line expressing Cre-dependent GFP-L10a ribosomal subunit fusion protein (Rosa26 eGFP-L10a ), and injected into NAc a persistent, retrograde viral vector expressing Cre (HSV-hEf1ɑ-Cre).…”

“…As previous findings demonstrated that increased activity in vHPC-NAc neurons underlies CSDS susceptibility 4 , we next sought to ascertain the role of ΔFosB in the physiological properties of the vHPC-NAc circuit. We first examined the effects of ΔFosB overexpression in putative glutamatergic pyramidal neurons of vCA1 via whole-cell, patch-clamp electrophysiology in ex vivo slice preparations 17,18 . Viral-mediated ΔFosB overexpression reduced the excitability of vCA1 neurons, indicated by a decrease in the number of current-elicited spikes across increasing step currents (Fig.…”

Differential expression of deltaFosB in reward processing regions between binge eating prone and resistant female rats

“…It has been shown that ΔFosB expression in the hippocampus also decreases neuronal activity [41]. We therefore conclude that the activity of ΔFosB-expressing neurons in both the mPFC and VTA would also decrease, and this decrease is greater in BEP than in BER rats.…”

“…In this region, GABAergic neurons inhibit the activity of dopaminergic neurons. ΔFosB reduces the activity of ΔFosB-expressing neurons [36, 41]. As the proportion of GABAergic ΔFosB-expressing neurons was lower in BEP rats, it suggests that the GABAergic neuronal activity is less reduced in BEP rats compared to BER rats.…”