Highly differentiated cellular and circuit properties of infralimbic pyramidal neurons projecting to the periaqueductal gray and amygdala

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.

Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear

“…These results show that the impact of vHPC input to pyramidal neurons in the IL is largely inhibitory, and largest to neurons in L2/3. Pyramidal neurons in the IL that project to the BLA are primarily located in L2/3 26,27 , so we tested whether vHPC input targets amygdala-projecting neurons in the IL, by combining optical HPC stimulation with retrograde bead injections into the basolateral and central amygdala (Fig. 1i,j).…”

Age‐dependent expression of Nav1.9 channels in medial prefrontal cortex pyramidal neurons in rats

“…Layer II and layer V pyramidal neurons differ in both their activity patterns (Boudewijns et al, ; van Aerde and Feldmeyer, ) and their morphology (Ferreira et al, ; van Aerde and Feldmeyer, ). Pyramidal neurons in these layers also possess different reciprocal connections with subcortical structures.…”

“…Pyramidal neurons in these layers also possess different reciprocal connections with subcortical structures. Layer II neurons project to the amygdala and receive strong synaptic input from the hippocampus (Dégenètais et al, ) and amygdala (Little and Carter, ), while layer V pyramidal neurons project to the periaqueductal gray (Ferreira et al, ) and receive input from the hippocampus (Dégenètais et al, ). Moreover, layer V pyramidal neurons seem to be more strictly controlled by acetylcholine (Gulledge et al, ) and adenosine A1 receptors (van Aerde et al, ) than layer II pyramidal neurons.…”

The central amygdala to periaqueductal gray pathway comprises intrinsically distinct neurons differentially affected in a model of inflammatory pain

“…; Ferreira et al . ). Therefore, we aimed to investigate whether a major output pathway of the CeA consists of a homogeneous population of neurons.…”