Patterns of theta activity in limbic anxiety circuit preceding exploratory behavior in approach-avoidance conflict

Theta oscillations within the hippocampus-amygdala-medial prefrontal cortex (HPC-AMY-mPFC) circuit have been consistently implicated in the regulation of anxiety behaviors, including risk-assessment. To study if theta activity during risk-assessment was correlated with exploratory behavior in an approach/avoidance paradigm we recorded simultaneous local field potentials from this circuit in rats exploring the elevated-plus maze (FPM). Opposing patterns of power variations in the ventral hippocampus (vHPC), basolateral amygdala (BLA), and prelimbic (PrL) mPFC, but not in the dorsal hippocampus (dHPC), during exploratory risk-assessment of the open arms preceded further exploration of the open arms or retreat back to the safer closed arms. The same patterns of theta power variations in the HPC-BLA-mPFC(PrL) circuit were also displayed by animals submitted to chronic unpredictable stress protocol known to induce an anxious state. Diverging patterns of vHPC-mPFC(PrL) theta coherence were also significantly correlated with forthcoming approach or avoidance behavior in the conflict situation in both controls and stressed animals; interestingly, vHPC-BLA, and BLA-mPFC(PrL) theta coherence correlated with future behavior only in stressed animals, underlying the pivotal role of the amygdala on the stress response.LJ was supported by fellowships: SFRH/BD/40459/2007 from the Portuguese Foundation for Science and Technology (FCT); UMINHO/BPD/27/2013 funded by CCDR-N and Programa Operational Regiao Norte (ON.2) from QREN/FEDER; and UMINHO/BPD/63/2015 from Fundacao Calouste Gulbenkian funded project (contract grant number P-139977). Financial support for this work was provided by FEDER funds through the Operational Programme Competitiveness Factors - COMPETE and National Funds through FCT under projects ECOMP-01-0124-FEDER-021145, FCT/PTDC/SAU-ENB/118383/2010, FCOMP-01-0124-FEDER-022674 and POCI-01-0145-FEDER-007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).