Biology subjects

Terrell, J. M.

Publications and source records attributed to Terrell, J. M..

2 recordsLinked to original sources

bioRxiv2024

The prelimbic prefrontal cortex mediates the development of lasting social phobia as a consequence of social threat conditioning.

Social phobia is highly detrimental for social behavior, mental health, and productivity. Despite much previous research, the behavioral and neurobiological mechanisms associated with the development of social phobia remain elusive. To investigate these issues, the present study implemented a mouse model of social threat conditioning in which mice received electric shock punishment upon interactions with unfamiliar conspecifics. This resulted in immediate reductions in social behavior and robust increases in defensive mechanisms such as avoidance, freezing, darting, and ambivalent stretched posture. Furthermore, social deficits lasted for prolonged periods and were independent of contextual settings, sex variables, or particular identity of the social stimuli. Shedding new light into the neurobiological factors contributing to this phenomenon, we found that optogenetic silencing of the prelimbic (PL), but not the infralimbic (IL), subregion of the medial prefrontal cortex (mPFC) during training led to subsequent forgetting and development of lasting social phobia. Similarly, pharmacological inhibition of NMDARs in PL also impaired the development of social phobia. These findings are consistent with the notion that social-related trauma is a prominent risk factor for the development of social phobia, and that this phenomenon engages learning-related mechanisms within the prelimbic prefrontal cortex to promote prolonged representations of social threat. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/597446v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1f72e5eorg.highwire.dtl.DTLVardef@1053c13org.highwire.dtl.DTLVardef@ab3528org.highwire.dtl.DTLVardef@2ee4d2_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

The infralimbic and prelimbic cortical areas bidirectionally regulate safety learning during normal and stress conditions.

Safety learning is a critical function for behavioral adaptation, environmental fitness, and mental health. Animal models have implicated the prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC) in safety learning. However, whether these regions differentially contribute to safety learning and how their contributions become affected by stress still remain poorly understood. In this study, we evaluated these issues using a novel semi-naturalistic mouse model for threat and safety learning. As mice navigated within a test arena, they learned that specific zones were associated with either noxious cold temperatures ("threat") or pleasant warm temperatures ("safety"). Optogenetic-mediated inhibition revealed critical roles for the IL and PL regions for selectively controlling safety learning during these naturalistic conditions. This form of safety learning was also highly susceptible to stress pre-exposure, and while IL inhibition mimicked the deficits produced by stress, PL inhibition fully rescued safety learning in stress-exposed mice. Collectively, these findings indicate that IL and PL bidirectionally regulate safety learning during naturalistic situations, with the IL region promoting this function and the PL region suppressing it, especially after stress. A model of balanced IL and PL activity is proposed as a fundamental mechanism for controlling safety learning. Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=51 SRC="FIGDIR/small/539516v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@b7bd5aorg.highwire.dtl.DTLVardef@f06849org.highwire.dtl.DTLVardef@14e9848org.highwire.dtl.DTLVardef@efc491_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗