Differential inhibition onto developing and mature granule cells generates high-frequency filters with variable gain

Pardi, María Belén; Ogando, Mora B.; Schinder, Alejandro F.; Marín‐Burgin, Antonia

doi:10.7554/elife.08764

Cited by 30 publications

(35 citation statements)

References 48 publications

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“…PV-IN synapses onto new GCs are formed early (Song et al, 2013) but, as shown here, synaptic responses mature during several weeks, becoming increasingly stronger and faster. The slow IPSC kinetics exhibited by young synapses may well explain the hyperexcited neuronal behavior described previously in 4-week old GCs (Marin-Burgin et al, 2012;Pardi et al, 2015).…”

Section: Discussionsupporting

confidence: 68%

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: 68%

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

Groisman

Yang

Schinder

2019

Preprint

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“…Activity of individual GCs in response to glutamatergic inputs is primarily restrained by powerful GABAergic inhibition26353637. We used extracellular recording techniques to examine the influence of GABAergic inhibition on the GC responses to the cortical input, the perforant path (PP).…”

Section: Resultsmentioning

confidence: 99%

“…We used extracellular recording techniques to examine the influence of GABAergic inhibition on the GC responses to the cortical input, the perforant path (PP). As described previously3638, we first calibrated the input strength in individual rodent brain slices in the presence of two field-recording electrodes: one electrode placed in the molecular layer (ML), for field excitatory postsynaptic potentials (fEPSPs), and one in the GC layer (GCL), for population spikes (pSpikes) (Fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

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Causal Evidence for the Role of Specific GABAergic Interneuron Types in Entorhinal Recruitment of Dentate Granule Cells

Lee¹,

Kao²,

Hou³

et al. 2016

Sci Rep

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The dentate gyrus (DG) is the primary gate of the hippocampus and controls information flow from the cortex to the hippocampus proper. To maintain normal function, granule cells (GCs), the principal neurons in the DG, receive fine-tuned inhibition from local-circuit GABAergic inhibitory interneurons (INs). Abnormalities of GABAergic circuits in the DG are associated with several brain disorders, including epilepsy, autism, schizophrenia, and Alzheimer disease. Therefore, understanding the network mechanisms of inhibitory control of GCs is of functional and pathophysiological importance. GABAergic inhibitory INs are heterogeneous, but it is unclear how individual subtypes contribute to GC activity. Using cell-type-specific optogenetic perturbation, we investigated whether and how two major IN populations defined by parvalbumin (PV) and somatostatin (SST) expression, regulate GC input transformations. We showed that PV-expressing (PV+) INs, and not SST-expressing (SST+) INs, primarily suppress GC responses to single cortical stimulation. In addition, these two IN classes differentially regulate GC responses to θ and γ frequency inputs from the cortex. Notably, PV+ INs specifically control the onset of the spike series, whereas SST+ INs preferentially regulate the later spikes in the series. Together, PV+ and SST+ GABAergic INs engage differentially in GC input-output transformations in response to various activity patterns.

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“…Indeed, at this stage, immature neurons show higher excitability than mature granule neurons (Mongiat, Espósito, Lombardi, & Schinder, 2009). New neurons can generate action potentials even upon weak input (Marín-Burgin, Mongiat, Pardi, & Schinder, 2012), allowing them to respond to a much wider range of stimuli (Pardi, Ogando, Schinder, & Marin-Burgin, 2015). The expression of these distinct properties of adult-born neurons is transient and may serve as a major mediator for experience-dependent plasticity in the hippocampus.…”

mentioning

confidence: 99%

Targeting hippocampal adult neurogenesis using transcription factors to reduce Alzheimer's disease‐associated memory impairments

2018

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Hippocampal adult neurogenesis results in the persisting formation of new neurons that contribute to hippocampal‐dependent learning and memory. This has led to the hypothesis that memory impairments associated with neurodegenerative diseases such as Alzheimer's disease may involve abnormal neurogenesis. Supporting this idea, evidence for decreased adult neurogenesis has been reported in the brain of Alzheimer's disease patients and in several mouse models of the disease. Thus, the development of strategies designed to stimulate the production of new neurons in the diseased brain has raised growing interest. In this review, we discuss putative strategies and present recent studies showing that it is now possible to instruct hippocampal endogenous neural progenitors to adopt an exclusive neuronal fate. We further report how such strategies lead to the rescue of cognitive functions in mouse models of Alzheimer's disease. Altogether, these findings provide the proof‐of‐concept that neurogenesis can be stimulated in the adult brain in vivo, and consequently overcomes pathological memory deficits.

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Differential inhibition onto developing and mature granule cells generates high-frequency filters with variable gain

Cited by 30 publications

References 48 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

Causal Evidence for the Role of Specific GABAergic Interneuron Types in Entorhinal Recruitment of Dentate Granule Cells

Targeting hippocampal adult neurogenesis using transcription factors to reduce Alzheimer's disease‐associated memory impairments

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