Differential Activity-Dependent Increase in Synaptic Inhibition and Parvalbumin Interneuron Recruitment in Dentate Granule Cells and Semilunar Granule Cells

Abstract

Strong inhibitory synaptic gating of dentate gyrus granule cells (GCs), attributed largely to fast-spiking parvalbumin interneurons (PV-INs), is essential to maintain sparse network activity needed for dentate dependent behaviors. However, the contribution of PV-INs to basal and input-driven sustained synaptic inhibition in GCs and semilunar granule cells (SGCs), a sparse morphologically distinct dentate projection neuron subtype, is currently unknown. In studies conducted in hippocampal slices from mice, we find that although basal IPSCs are more frequent in SGCs and optical activation of PV-INs reliably elicited IPSCs in both GCs and SGCs, optical suppression of PV-INs failed to reduce IPSC frequency in either cell type. Amplitude and kinetics of IPSCs evoked by perforant path (PP) activation were not different between GCs and SGCs. However, the robust increase in sustained polysynaptic IPSCs elicited by paired afferent stimulation was lower in SGCs than in simultaneously recorded GCs. Optical suppression of PV-IN selectively reduced sustained IPSCs in SGCs but not in GCs. These results demonstrate that PV-INs, while contributing minimally to basal synaptic inhibition in both GCs and SGCs in slices, mediate sustained feedback inhibition selectively in SGCs. The temporally selective blunting of activity-driven sustained inhibitory gating of SGCs could support their preferential and persistent recruitment during behavioral tasks.

Reclusive Chandeliers: Functional Isolation of Dentate Axo-Axonic Cells After Experimental Status Epilepticus

“…Morphologically identified AACs had multipolar somata in the IML and, typically, extended prominent apical dendrites reaching fissure and a few had basal dendrites in the hilus suggesting that AACs could contribute to both feedforward and feedback GC inhibition. 3D confocal imaging revealed extensive dendritic arborization along the z-plane distinguishing the dendritic structure of AACs from semilunar granule cells in the IML (Afrasiabi et al ., 2022; Gupta et al ., 2020).…”

“…3D confocal imaging revealed extensive dendritic arborization along the z-plane distinguishing the dendritic structure of AACs from semilunar granule cells in the IML (Afrasiabi et al, 2022;Gupta et al, 2020).…”

Early Deficits in Dentate Circuit and Behavioral Pattern Separation after Concussive Brain Injury

“…Naive C57BL6/J mice and mice one week after FPI or sham injury were anesthetized with isoflurane and decapitated for slice preparation using established protocols (Korgaonkar et al, 2020b; Afrasiabi et al, 2021). Horizontal brain slices (300 µm) were prepared in ice-cold sucrose artificial CSF (sucrose-aCSF) containing the following (in mM): 85 NaCl, 75 sucrose, 24 NaHCO 3 , 25 glucose, 4 MgCl 2 , 2.5 KCl, 1.25 NaH 2 PO 4 , and 0.5 CaCl 2 using a Leica VT1200S Vibratome (Wetzlar, Germany).…”

Long-Term Effects of Moderate Concussive Brain Injury During Adolescence on Synaptic and Tonic GABA Currents in Dentate Granule Cells and Semilunar Granule Cells

“…Sections were imaged using a Zeiss LSM 510 confocal microscope for classification. Images of biocytin-filled cells ( Figures 1C,D ) were used to distinguish GCs with compact dendritic arbors and hilar axonal projections from SGCs with wide dendritic angle, multiple primary dendrites, and axons projecting to the hilus ( Gupta et al, 2020 ; Afrasiabi et al, 2021 ). A subset of cells were reconstructed using Neurolucida 360 for illustration ( Gupta et al, 2020 ).…”

“…In addition to GCs, we reported that brain injury impacts inhibition of semilunar granule cells (SGCs), a sparse, morphologically distinct dentate projection neuron ( Williams et al, 2007 ; Gupta et al, 2012 ; Afrasiabi et al, 2021 ). SGCs have been proposed to support the feedback inhibition of GCs needed to maintain sparse activity and contribute to cellular memory representations ( Larimer and Strowbridge, 2010 ; Erwin et al, 2020 ).…”