Recruitment of parvalbumin and somatostatin interneuron inputs to adult born dentate granule neurons

Christine L Remmers,Charlotte C M Castillon,Anis Contractor,John N Armstrong

doi:10.1038/s41598-020-74385-2

Christine L Remmers, Charlotte C M Castillon + Show 2 more

Open Access

https://doi.org/10.1038/s41598-020-74385-2

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Journal: Scientific Reports	Publication Date: Oct 16, 2020
Citations: 4	License type: open-access

Affiliation: Northwestern University

Abstract

GABA is a key regulator of adult-born dentate granule cell (abDGC) maturation so mapping the functional connectivity between abDGCs and local interneurons is required to understand their development and integration into the hippocampal circuit. We recorded from birthdated abDGCs in mice and photoactivated parvalbumin (PV) and somatostatin (SST) interneurons to map the timing and strength of inputs to abDGCs during the first 4 weeks after differentiation. abDGCs received input from PV interneurons in the first week, but SST inputs were not detected until the second week. Analysis of desynchronized quantal events established that the number of GABAergic synapses onto abDGCs increased with maturation, whereas individual synaptic strength was constant. Voluntary wheel running in mice scaled the GABAergic input to abDGCs by increasing the number of synaptic contacts from both interneuron types. This demonstrates that GABAergic innervation to abDGCs develops during a prolonged post-mitotic period and running scales both SST and PV synaptic afferents.

Highlights

GABA is a key regulator of adult-born dentate granule cell maturation so mapping the functional connectivity between abDGCs and local interneurons is required to understand their development and integration into the hippocampal circuit
Retrograde transynaptic tracing has demonstrated that somatostatin (SST) and parvalbumin (PV) expressing interneurons synapse onto 3–5-week-old abDGCs9 and cholecystokinin (CCK) expressing interneurons synapse onto 5–7-week-old abDGCs10
Using PV-ChR2 and SST-ChR2 mice we studied the functional development of GABAergic synapses from these two interneuron types to abDGCs

Summary

Introduction

GABA is a key regulator of adult-born dentate granule cell (abDGC) maturation so mapping the functional connectivity between abDGCs and local interneurons is required to understand their development and integration into the hippocampal circuit. Functional inhibitory connections have been established between abDGCs and PV interneurons 4 and 10 days after differentiation[5,11], SST interneurons 3 weeks after differentiation[12], molecular layer performant path (MOPP) interneurons 3–4 weeks after d ifferentiation[9] as well as Ivy/neurogliaform c ells[13] in POMC-GFP labeled abDGCs that are approximately 2-weeks-old[14] Despite this there has not been a more detailed analysis of development of GABAergic afferents onto abDGCs during the first few weeks after differentiation. Two of the most abundant populations of local GABAergic interneurons in the dentate gyrus are PV and SST expressing cells[15] Both of these types of interneurons have been demonstrated to be synaptically connected to abDGCs5,9,12, the timing of formation of these synaptic contacts in immature abDGCs and how they are modulated by activity during the first 4 weeks following mitosis has not been extensively mapped. Given the distinct location of their axonal projections it is possible that PV and SST interneurons within the dentate form synapses differentially onto abDGCs as they migrate into the granule cell layer and extend their dendrites into the molecular layer

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