GABA Is Depolarizing in Hippocampal Dentate Granule Cells of the Adolescent and Adult Rats

Chiang, Pai Kai; Wu, Pu-Yeh; Kuo, Tzu Wei; Liu, Yu‐Chao; Chan, Chu Fang; Chien, Ta Chun; Cheng, Jen-Kun; Huang, Yu-Ren; Chiu, Cheng-Di; Lien, Cheng Chang

doi:10.1523/jneurosci.3393-11.2012

Cited by 58 publications

(48 citation statements)

References 29 publications

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“…3F). Therefore, it is likely that FBI reduces spiking without modifying the excitatory synaptic gain (consistent with a perisomatic action) or, alternatively, that the reduction in fEPSP may be masked by the shunting depolarization exerted by GABA in GCs (Andersen et al, 2007; Chiang et al, 2012; Sauer et al, 2012). These results demonstrate that activation of few mature adult-born GCs can greatly restrict the size of the spiking population, thus contributing to the sparse activation of the GCL.…”

Section: Resultsmentioning

confidence: 99%

Delayed Coupling to Feedback Inhibition during a Critical Period for the Integration of Adult-Born Granule Cells

Temprana

Mongiat

Yang

et al. 2015

Neuron

187

235

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SUMMARY Developing granule cells (GCs) of the adult dentate gyrus undergo a critical period of enhanced activity and synaptic plasticity before becoming mature. The impact of developing GCs on the activity of preexisting dentate circuits remains unknown. Here we combine optogenetics, acute slice electrophysiology, and in vivo chemogenetics to activate GCs at different stages of maturation to study the recruitment of local target networks. We show that immature (four-week-old) GCs can efficiently drive distal CA3 targets, but poorly activate proximal interneurons responsible for feedback inhibition (FBI). As new GCs transition towards maturity, they reliably recruit GABAergic feedback loops that restrict spiking of neighbor GCs, a mechanism that would promote sparse coding. Such inhibitory loop impinges only weakly in new cohorts of young GCs. A computational model reveals that the delayed coupling of new GCs to FBI could be crucial to achieve a fine-grain representation of novel inputs in the dentate gyrus.

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Section: Resultsmentioning

confidence: 99%

Delayed Coupling to Feedback Inhibition during a Critical Period for the Integration of Adult-Born Granule Cells

Temprana

Mongiat

Yang

et al. 2015

Neuron

187

235

View full text Add to dashboard Cite

show abstract

“…These findings are significant in terms of the diversity of mechanism with which GABA-mediated Cl À currents can modulate neural activity. Examples of GABAmediated depolarization in the adult nervous system under normal, non-pathological conditions have now been reported in a wide range of invertebrate species (Norekian and Malyshev, 2005;Cheung et al, 2006;Pfeiffer et al, 2009) and regions of the vertebrate CNS (Duchen, 1986;Chavas and Marty, 2003;Ruiz et al, 2003;Szabadics et al, 2006;Adermark et al, 2009;Pugh and Jahr, 2011;Chiang et al, 2012). In many of these studies GABA-mediated depolarization was excitatory, but there are also examples of GABA depolarization having an inhibitory effect due to either current shunting or Na + channel inactivation (Willis, 1999;Song et al, 2011;Witschi et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of GABA in modulating nociceptive vs. non-nociceptive synapses

et al. 2015

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GABA (γ-amino-butyric acid) -mediated signaling is normally associated with synaptic inhibition due to ionotropic GABA receptors that gate an inward Cl(-) current, hyperpolarizing the membrane potential. However, there are also situations where ionotropic GABA receptors trigger a Cl(-) efflux that results in depolarization. The well-characterized central nervous system of the medicinal leech was used to study the functional significance of opposing effects of GABA at the synaptic circuit level. Specifically, we focused on synapses made by the nociceptive N cell and the non-nociceptive P (pressure) cell that converge onto a common postsynaptic target. It is already known that GABA hyperpolarizes the P cell, but depolarizes the N cell and that inhibition of ionotropic GABA receptors by bicuculline (BIC) has opposing effects on the synapses made by these two inputs; enhancing P cell synaptic transmission, but depressing N cell synapses. The goal of the present study was to determine whether the opposing effects of GABA were due to differences in Cl(-) homeostasis between the two presynaptic neurons. VU 0240551 (VU), an inhibitor of the Cl(-) exporter K-Cl co-transporter isoform 2 (KCC2), attenuated GABA-mediated hyperpolarization of the non-nociceptive afferent while bumetanide (BUM), an inhibitor of the Cl(-) importer Na-K-Cl co-transporter isoform 1 (NKCC1), reduced GABA-mediated depolarization of the nociceptive neuron. VU treatment also enhanced P cell synaptic signaling, similar to the previously observed effects of BIC and consistent with the idea that GABA inhibits synaptic signaling at the presynaptic level. BUM treatment depressed N cell synapses, again similar to what is observed following BIC treatment and suggests that GABA has an excitatory effect on these synapses. The opposing effects of GABA could also be observed at the behavioral level with BIC and VU increasing responsiveness to non-nociceptive stimulation while BIC and BUM decreased responsiveness to nociceptive stimulation. These findings demonstrate that distinct synaptic inputs within a shared neural circuit can be differentially modulated by GABA in a functionally relevant manner.

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“…GABA is depolarizing at this time (due to immature, high internal chloride concentration), but when exogenously applied inhibits cell firing via shunting (Overstreet-Wadiche et al 2005). (Interestingly, because of their hyperpolarized resting potential, GABA is also depolarizing and shunting in matGCs [Chiang et al 2012;Sauer et al 2012]). The final event in GABAergic innervation of abGCs, occurring at 3-wk post-mitosis, seems to be functional connectivity to perisomatic basket cells that mediate large, fast IPSCs (Espó sito et al 2005).…”

Section: Afferent Synaptic Connectivitymentioning

confidence: 99%

Adult neurogenesis in the mammalian hippocampus: Why the dentate gyrus?

2013

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In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity after the perinatal period suggests that unique aspects of the structure and function of DG and olfactory bulb circuits allow them to benefit from the adult generation of neurons. In this review, we consider the distinctive features of the DG that may account for it being able to profit from this singular form of neural plasticity. Approaches to the problem of neurogenesis are grouped as “bottom-up,” where the phenotype of adult-born granule cells is contrasted to that of mature developmentally born granule cells, and “top-down,” where the impact of altering the amount of neurogenesis on behavior is examined. We end by considering the primary implications of these two approaches and future directions.

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GABA Is Depolarizing in Hippocampal Dentate Granule Cells of the Adolescent and Adult Rats

Cited by 58 publications

References 29 publications

Delayed Coupling to Feedback Inhibition during a Critical Period for the Integration of Adult-Born Granule Cells

Delayed Coupling to Feedback Inhibition during a Critical Period for the Integration of Adult-Born Granule Cells

Differential effects of GABA in modulating nociceptive vs. non-nociceptive synapses

Adult neurogenesis in the mammalian hippocampus: Why the dentate gyrus?

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