Abstract
The infralimbic (IL) cortex is a key node in an inter-connected network involved in fear and emotion processing. The cellular and circuit-level mechanisms whereby IL neurons receive, filter, and modulate incoming signals they project onward to diverse downstream nodes in this complex network remain poorly understood. Using the mouse as our model, we applied anatomical labeling strategies, brain slice electrophysiology, and focal activation of caged glutamate via laser scanning photostimulation (glu-LSPS) for quantitative neurophysiological analysis of projectionally defined neurons in IL. Injection of retrograde tracers into the periaqueductal gray (PAG) and basolateral amygdala (BLA) was used to identify cortico-PAG (CP) and cortico-BLA (CA) neurons in IL. CP neurons were found exclusively in layer 5 (L5) of IL whereas CA neurons were detected throughout layer 2, 3, and 5 of IL. We also identified a small percentage of IL neurons that project to both the PAG and the BLA. We found that L5 CP neurons have a more extensive dendritic structure compared to L5 CA neurons. Neurophysiological recordings performed on retrogradely labeled neurons in acute brain slice showed that CP and CA neurons in IL could be broadly classified in two groups: neuronal resonators and non-resonators. Layer 2 CA neurons were the only class that was exclusively non-resonating. CP, CA, and CP/CA neurons in layers 3 and 5 of IL consisted of heterogeneous populations of resonators and non-resonators showing that projection target is not an exclusive predictor of intrinsic physiology. Circuit mapping using glu-LSPS revealed that the strength and organization of local excitatory and inhibitory inputs were stronger to CP compared to CA neurons in IL. Together, our results establish an organizational scheme linking cellular neurophysiology with microcircuit parameters of defined neuronal subclasses in IL that send descending commands to subcortical structures involved in fear behavior.
Highlights
IntroductionThe medial prefrontal cortex (mPFC) is critical for processing emotional responses
The medial prefrontal cortex is critical for processing emotional responses
We found that CP and CA neurons in layer 5 (L5) of infralimbic cortex (IL) were in close proximity (Figure 2B) and that a small percentage of IL neurons were labeled with both retrograde tracers (Figure 2C) These results show IL output pathways to the periaqueductal gray (PAG) and basolateral amygdala (BLA) consist primarily of neighboring populations neurons in layer 2 (L2)–L5 of IL, but with a small subset of L5 neurons projecting to both subcortical structures
Summary
The medial prefrontal cortex (mPFC) is critical for processing emotional responses. Across the cortex, including mPFC, L5 contains a heterogeneous population of pyramidal neurons that have distinct local circuit organization, firing properties, interconnectivity, morphology, and neuromodulation based on long-range projection target (Molnar and Cheung, 2006; Morishima and Kawaguchi, 2006; Wang et al, 2006; Le Be et al, 2007; Brown and Hestrin, 2009; Anderson et al, 2010; Dembrow et al, 2010; Morishima et al, 2011; Sheets et al, 2011; Kiritani et al, 2012; Oswald et al, 2013). The specific dynamics and circuit organization of neurons comprising descending IL output that contributes to fear perception and the corresponding conditioned response remains unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
