Somatostatin-positive interneurons in the dentate gyrus of mice provide local- and long-range septal synaptic inhibition

Yuan, Man; Meyer, Thomas; Benkowitz, Christoph; Savanthrapadian, Shakuntala; Ansel-Bollepalli, Laura; Foggetti, Angelica; Wulff, Peer; Alcamí, Pepe; Elgueta, Claudio; Bartos, Marlene

doi:10.7554/elife.21105

Cited by 79 publications

(121 citation statements)

References 96 publications

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“…In this context, we speculate that proximal and distal synapses derive from individual populations of SST-INs that target different cellular compartments. In fact, two subtypes of SST-INs were recently reported in the DG and might underlie the responses observed here; hilar-perforant-path-associated INs with axon fibers in the molecular layer that make distal synapses, and INs with axons in the hilus that provide perisomatic inhibition (Yuan et al, 2017).…”

Section: Discussionsupporting

confidence: 60%

Differential coupling of adult-born granule cells to parvalbumin and somatostatin interneurons

Groisman

Yang

Schinder

2019

Preprint

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The dentate gyrus of the hippocampus is dominated by a strong GABAergic tone that maintains sparse levels of activity. Adult neurogenesis disrupts this balance through the continuous addition of new granule cells (GCs) that display high excitability while develop and connect within the preexisting host circuit. The dynamics of the connectivity map for developing GCs in the local inhibitory networks remains unknown. We used optogenetics to study afferent and efferent synaptogenesis between new GCs and GABAergic interneurons expressing parvalbumin (PV-INs) and somatostatin (SST-INs). Inputs from PV-INs targeted the soma and remained immature until they grew abruptly in >4-week-old GCs. This transition was accelerated by exposure to enriched environment. Inputs from SST-INs were dendritic and developed slowly until reaching maturity by 8 weeks. Synaptic outputs from GCs onto PV-INs matured faster than those onto SST-INs, but also required several weeks. In the mature dentate network, PV-INs exerted an efficient control of GC spiking and were involved in both feedforward and feedback loops, a mechanism that would favor lateral inhibition and sparse coding. Our results reveal a long-lasting transition where adult-born neurons remain poorly coupled to inhibition, which might enable a parallel streaming channel from the entorhinal cortex to CA3 pyramidal cells.

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Section: Discussionsupporting

confidence: 60%

Differential coupling of adult-born granule cells to parvalbumin and somatostatin interneurons

Groisman

Yang

Schinder

2019

Preprint

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“…Parvalbumin + interneurons in the subgranular zone act to inhibit neurogenesis through spill-over of GABA (Song et al 2012). In addition, a small subset of somatostatin + interneurons with cell bodies in the hilus and dendrites that project to the molecular layer inhibit neurons locally and in the medial septum and diagonal band of Broca (MS/DBB) (Yuan et al 2017) which could be impacting adult neurogenesis. Interestingly, parvalbumin + interneurons receive input from the MS/DBB (Bao et al 2017), and loss of this input causes activation of NSCs with a decline in NSC pools.…”

Section: Discussionmentioning

confidence: 99%

The α7 nicotinic acetylcholine receptors regulate hippocampal adult-neurogenesis in a sexually dimorphic fashion

Otto

Yakel

2018

Brain Struct Funct

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Disruption in cholinergic signaling has been linked to many environmental and/or pathological conditions known to modify adult neurogenesis. The α7 nAChRs are in the family of cys-loop receptor channels which have been shown to be neuroprotective in adult neurons and are thought to be critical for survival and integration of immature neurons. However, in developing neurons, poor calcium buffering may cause α7 nAChR activation to be neurotoxic. To investigate whether the α7 nAChR regulates neurogenesis in the hippocampus, we used a combination of mouse genetics and imaging to quantify neural stem cell (NSC) densities located in the dentate gyrus of adult mice. In addition, we considered whether the loss of α7 nAChRs had functional consequences on a spatial discrimination task that is thought to rely on pattern separation mechanisms. We found that the loss of α7 nAChRs resulted in increased neurogenesis in male mice only, while female mice showed increased cell divisions and intermediate progenitors but no change in neurogenesis. Knocking out the α7 nAChR from nestin+ NSCs and their progeny showed signaling in these cells contributes to regulating neurogenesis. In addition, male, but not female, mice lacking α7 nAChRs performed significantly worse in the spatial discrimination task. This task was sexually dimorphic in wild-type mice, but not in the absence of α7 nAChRs. We conclude that α7 nAChRs regulate adult neurogenesis and impact spatial discrimination function in male, but not female mice, via a mechanism involving nestin+ NSCs and their progeny.

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“…Lesions of the ventral, but not dorsal, hippocampus and dentate gyrus (DG) in rats, reduced anxiety-like behavior and increased time spent in the aversive open arms of the elevated plus maze (EPM) (Kjelstrup et al, 2002;Weeden, Roberts, Kamm, & Kesner, 2014), while increased activity in ventral hippocampus (vHip) has been associated with anxious behavior (Adhikari, Topiwala, & Gordon, 2010. These and other studies suggest vHip is crucial for mediating anxious behavior (Fanselow & Dong, 2010), and details of the precise networks and neural populations involved are beginning to be identified (Calhoon & Tye, 2015;Çalışkan et al, 2016;Felix-Ortiz et al, 2013;Li, Bartley, & Dobrunz, 2017;Lovett-Barron et al, 2014;Padilla-Coreano et al, 2016;Stefanelli, Bertollini, Luscher, Muller, & Mendez, 2016;Yeung, Engin, & Treit, 2011;Yuan et al, 2017). At a neurochemical level, anxiety is correlated with dysfunctions in hippocampal inhibitory interneuron network activity (Engin & Treit, 2007;Kalueff, 2007).…”

mentioning

confidence: 99%

Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

et al. 2019

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Anxiety disorders are highly prevalent in modern society and better treatments are required. Key brain areas and signaling systems underlying anxiety include prefrontal cortex, hippocampus, and amygdala, and monoaminergic and peptidergic systems, respectively. Hindbrain GABAergic projection neurons that express the peptide, relaxin‐3, broadly innervate the forebrain, particularly the septum and hippocampus, and relaxin‐3 acts via a Gi/o‐protein‐coupled receptor known as the relaxin‐family peptide 3 receptor (RXFP3). Thus, relaxin‐3/RXFP3 signaling is implicated in modulation of arousal, motivation, mood, memory, and anxiety. Ventral hippocampus (vHip) is central to affective and cognitive processing and displays a high density of relaxin‐3‐positive nerve fibers and RXFP3 binding sites, but the identity of target neurons and associated effects on behavior are unknown. Therefore, in adult, male rats, we assessed the neurochemical nature of hippocampal RXFP3 mRNA‐expressing neurons and anxiety‐like and social behavior following chronic RXFP3 activation in vHip by viral vector expression of an RXFP3‐selective agonist peptide, R3/I5. RXFP3 mRNA detected by fluorescent in situ hybridization was topographically distributed across the hippocampus in somatostatin‐ and parvalbumin‐mRNA expressing GABA neurons. Chronic RXFP3 activation in vHip increased anxiety‐like behavior in the light–dark box and elevated‐plus maze, but not the large open‐field test, and reduced social interaction with a conspecific stranger. Our data reveal disruptive effects of persistent RXFP3 signaling on hippocampal GABA networks important in anxiety; and identify a potential therapeutic target for anxiety disorders that warrants further investigation in relevant preclinical models.

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Somatostatin-positive interneurons in the dentate gyrus of mice provide local- and long-range septal synaptic inhibition

Cited by 79 publications

References 96 publications

Differential coupling of adult-born granule cells to parvalbumin and somatostatin interneurons

Differential coupling of adult-born granule cells to parvalbumin and somatostatin interneurons

The α7 nicotinic acetylcholine receptors regulate hippocampal adult-neurogenesis in a sexually dimorphic fashion

Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

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