Perisomatic inhibition profoundly controls neural function. However, the structural
organization of inhibitory circuits giving rise to the perisomatic inhibition in the
higher-order cortices is not completely known. Here, we performed a comprehensive
analysis of those GABAergic cells in the medial prefrontal cortex (mPFC) that provide
inputs onto the somata and proximal dendrites of pyramidal neurons. Our results show
that most GABAergic axonal varicosities contacting the perisomatic region of superficial
(layer 2/3) and deep (layer 5) pyramidal cells express parvalbumin (PV) or cannabinoid
receptor type 1 (CB1). Further, we found that the ratio of PV/CB1 GABAergic inputs
is larger on the somatic membrane surface of pyramidal tract neurons in comparison
with those projecting to the contralateral hemisphere. Our morphologic analysis ofin
vitrolabeled PV+ basket cells (PVBC) and CCK/CB1+ basket cells (CCKBC)
revealed differences in many features. PVBC dendrites and axons arborized preferentially
within the layer where their soma was located. In contrast, the axons of CCKBCs expanded
throughout layers, although their dendrites were found preferentially either in superficial
or deep layers. Finally, using anterograde trans-synaptic tracing we observed that
PVBCs are preferentially innervated by thalamic and basal amygdala afferents in layers
5a and 5b, respectively. Thus, our results suggest that PVBCs can control the local
circuit operation in a layer-specific manner via their characteristic arborization,
whereas CCKBCs rather provide cross-layer inhibition in the mPFC.SIGNIFICANCE
STATEMENTInhibitory cells in cortical circuits are crucial for the precise
control of local network activity. Nevertheless, in higher-order cortical areas that
are involved in cognitive functions like decision-making, working memory, and cognitive
flexibility, the structural organization of inhibitory cell circuits is not completely
understood. In this study we show that perisomatic inhibitory control of excitatory
cells in the medial prefrontal cortex is performed by two types of basket cells endowed
with different morphologic properties that provide inhibitory inputs with distinct
layer specificity on cells projecting to disparate areas. Revealing this difference
in innervation strategy of the two basket cell types is a key step toward understanding
how they fulfill their distinct roles in cortical network operations.
