PT  - JOURNAL ARTICLE
AU  - Laura Rovira-Esteban
AU  - Norbert Hájos
AU  - Gergő Attila Nagy
AU  - Carlos Crespo
AU  - Juan Nacher
AU  - Emilio Varea
AU  - José Miguel Blasco-Ibáñez
TI  - Semilunar granule cells are the primary source of the perisomatic excitatory innervation onto parvalbumin-expressing interneurons in the dentate gyrus
AID  - 10.1523/ENEURO.0323-19.2020
DP  - 2020 Jun 22
TA  - eneuro
PG  - ENEURO.0323-19.2020
4099  - http://www.eneuro.org/content/early/2020/06/22/ENEURO.0323-19.2020.short
4100  - http://www.eneuro.org/content/early/2020/06/22/ENEURO.0323-19.2020.full
AB  - We analyzed the origin and relevance of the perisomatic excitatory inputs on the parvalbumin interneurons of the granule cell layer in mouse. Confocal analysis of the glutamatergic innervation showed that it represents about 50% of the perisomatic synapses that parvalbumin cells receive. This excitatory input may originate from granule cell collaterals, the mossy cells, or even supramammillary nucleus. First, we assessed the input from the mossy cells on parvalbumin interneurons. Axon terminals of mossy cells were visualized by their calretinin content. Using multicolor confocal microscopy, we observed that less than 10% of perisomatic excitatory innervation of parvalbumin cells could originate from mossy cells. Correlative light and electron microscopy revealed that innervation from mossy cells, although present, was indeed infrequent, except for those parvalbumin cells whose somata were located in the inner molecular layer. Second, we investigated the potential input from supramammillary nucleus on parvalbumin cell somata using anterograde tracing or immunocytochemistry against vesicular glutamate transporter 2 (VGLUT2) and found only occasional contacts. Third, we intracellularly filled dentate granule cells in acute slice preparations using whole-cell recording and examined whether their axon collaterals target parvalbumin interneurons. We found that typical granule cells do not innervate the perisomatic region of these GABAergic cells. In sharp contrast, semilunar granule cells, a scarce granule cell subtype often contacted the parvalbumin cell soma and proximal dendrites. Our data, therefore, show that perisomatic excitatory drive of parvalbumin interneurons in the granular layer of the dentate gyrus is abundant and originates primarily from semilunar granule cells.Significance Statement The microcircuitry underlying each cerebral structure is important to understand its function in normal and pathological conditions. We analyzed the excitatory innervation on the soma of the parvalbumin-expressing interneurons in the dentate gyrus. Excitatory innervation on the soma is in a privileged position to drive more efficiently the spiking of neurons than that on dendrites. How parvalbumin interneurons are recruited is crucial for a proper knowledge of the function that they play in dentate gyrus operation. Our results show that the main source of this innervation are the semilunar granule cells, a rare subtype of granule cells. Thus, this scarce excitatory cell type of the dentate gyrus is in a strategic position to effectively control network operation via feed-forward inhibition.