title: Trace Fear Conditioning Differentially Modulates Intrinsic Excitability of Medial Prefrontal Cortex-Basolateral Complex of Amygdala Projection Neurons in Infralimbic and Prelimbic Cortices.
abstract: Neuronal activity in medial prefrontal cortex (mPFC) is critical for the formation of trace fear memory, yet the cellular mechanisms underlying these memories remain unclear. One possibility involves the modulation of intrinsic excitability within mPFC neurons that project to the basolateral complex of amygdala (BLA). The current study used a combination of retrograde labeling and in vitro whole-cell patch-clamp recordings to examine the effect of trace fear conditioning on the intrinsic excitability of layer 5 mPFC-BLA projection neurons in adult rats. Trace fear conditioning significantly enhanced the intrinsic excitability of regular spiking infralimbic (IL) projection neurons, as evidenced by an increase in the number of action potentials after current injection. These changes were also associated with a reduction in spike threshold and an increase in h current. In contrast, trace fear conditioning reduced the excitability of regular spiking prelimbic (PL) projection neurons, through a learning-related decrease of input resistance. Interestingly, the amount of conditioned freezing was (1) positively correlated with excitability of IL-BLA projection neurons after conditioning and (2) negatively correlated with excitability of PL-BLA projection neurons after extinction. Trace fear conditioning also significantly enhanced the excitability of burst spiking PL-BLA projection neurons. In both regions, conditioning-induced plasticity was learning specific (observed in conditioned but not in pseudoconditioned rats), flexible (reversed by extinction), and transient (lasted <10 d). Together, these data suggest that intrinsic plasticity within mPFC-BLA projection neurons occurs in a subregion- and cell-type-specific manner during acquisition, consolidation, and extinction of trace fear conditioning. Significance statement: Frontal lobe-related function is vital for a variety of important behaviors, some of which decline during aging. This study involves a novel combination of electrophysiological recordings from fluorescently labeled mPFC-to-amygdala projection neurons in rats with acquisition and extinction of trace fear conditioning to determine how specific neurons change during behavior. This is the first study to demonstrate that trace fear conditioning significantly alters the intrinsic excitability of mPFC-to-amygdala projection neurons in a subregion- and cell-type-specific manner, which is also transient and reversed by extinction. These data are of broad interest to the neuroscientific community, and the results will inspire additional studies investigating the cellular mechanisms underlying circuit-specific changes within the brain as a result of associative learning and memory.
authors.affiliation: Departments of Psychology and.
authors.forename: Chenghui
authors.identifier: http://orcid.org/0000-0003-3289-809X
authors.initials: C
authors.lastname: Song
authors.affiliation: Departments of Psychology and.
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Ehlers
authors.affiliation: Departments of Psychology and Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201 jrmoyer@uwm.edu.
authors.forename: James R
authors.initials: JR
authors.lastname: Moyer
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000502:physiology*; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology*; D055724:Electrophysiological Phenomena / Q000502:physiology; D005108:Extinction, Psychological; D005239:Fear / Q000502:physiology*; D007858:Learning / Q000502:physiology; D008032:Limbic System / Q000166:cytology / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344
keywords: amygdala; associative learning; consolidation; extinction; medial prefrontal cortex; memory