Stress-induced plasticity of GABAergic inhibition

Maguire, Jamie

doi:10.3389/fncel.2014.00157

Cited by 85 publications

(68 citation statements)

References 81 publications

(120 reference statements)

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“…The regulatory mechanisms of [Cl − ] i are involved in a wide range of acute neuronal insults, such as ischemia or traumatic injury, as well as in chronic disorders, including epilepsy, autism, and Down syndrome. Regulation of [Cl − ] i is also a major player in the control of neuroendocrine responses (54)(55)(56), and a very recent study puts KCC2 in key position in synaptic plasticity mechanisms that are likely to underlie cognitive impairment during senescence (57). These wide-ranging observations extend the scope and impact of technical advances in in vivo Cl − imaging.…”

Section: Discussionmentioning

confidence: 95%

Simultaneous two-photon imaging of intracellular chloride concentration and pH in mouse pyramidal neurons in vivo

Sato

Artoni

Landi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

128

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Intracellular chloride ([Cl−] i ) and pH (pH i ) are fundamental regulators of neuronal excitability. They exert wide-ranging effects on synaptic signaling and plasticity and on development and disorders of the brain. The ideal technique to elucidate the underlying ionic mechanisms is quantitative and combined two-photon imaging of [Cl − ] i and pH i , but this has never been performed at the cellular level in vivo. Here, by using a genetically encoded fluorescent sensor that includes a spectroscopic reference (an element insensitive to Cl − and pH), we show that ratiometric imaging is strongly affected by the optical properties of the brain. We have designed a method that fully corrects for this source of error. Parallel measurements of [Cl − ] i and pH i at the single-cell level in the mouse cortex showed the in vivo presence of the widely discussed developmental fall in [Cl − ] i and the role of the K-Cl cotransporter KCC2 in this process. Then, we introduce a dynamic twophoton excitation protocol to simultaneously determine the changes of pH i and [Cl − ] i in response to hypercapnia and seizure activity.I ntracellular ion concentrations are controlled by plasmalemmal transporters and channels, which generate and dissipate ionic electrochemical gradients, respectively (1). In recent years, regulation of the intracellular Cl − concentration ([Cl − ] i ) in neurons has attracted lots of attention, because it is the main ion that carries current across GABA A (and also, glycine) receptors. Changes in [Cl − ] i exert an immediate effect on the reversal potential of GABAergic currents (E GABA ) and, thereby, on the properties of GABA A receptor-mediated transmission (2-4). The "ionic plasticity" of GABAergic signaling involves not only the passive flux of Cl − ions through membrane channels but also, a number of ion transporters that regulate [Cl − ] i . Furthermore, this mechanism is under the control of intracellular signaling cascades that regulate the expression patterns as well as functional properties of ion transporters and channels (5, 6). With regard to long-term ionic modulation of GABAergic transmission, a case in point is the decrease in [Cl − ] i that is generally thought to take place during maturation of most central neurons. According to this widely accepted scenario, the Na-K-2Cl cotransporter NKCC1 accumulates Cl − in immature neurons, thereby promoting depolarizing GABA responses (3, 7-9), which is followed by developmental upregulation of the neuron-specific K-Cl cotransporter KCC2 that is required for the generation of classical hyperpolarizing inhibitory postsynaptic potentials (IPSPs) (10).A wealth of electrophysiological evidence dating back to the work in vivo by Eccles and coworkers (11) has provided evidence for active regulation of [Cl − ] i in mammalian central neurons and its crucial effect on the driving force of Cl − in inhibitory synapses (1). However, thus far, there are no direct data on neuronal [Cl − ] i measured in vivo at the single-cell level in the living brain, and for in...

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Section: Discussionmentioning

confidence: 95%

Simultaneous two-photon imaging of intracellular chloride concentration and pH in mouse pyramidal neurons in vivo

Sato

Artoni

Landi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

128

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“…Altered chloride transporter expression has been observed following neuronal stress (Wake et al, 2007), acute stress in rodents (Maguire, 2014; Sarkar et al, 2011), and seizures (Toole et al, 2014), suggesting GABA physiology is susceptible to environmental influence. We provide evidence that prenatal stress shifts mRNA expression in the BLA away from Kcc2 and towards Nkcc1 .…”

Section: Discussionmentioning

confidence: 99%

“…During postnatal development, BLA neurophysiology is highly dynamic (Ehrlich et al, 2012; Thompson et al, 2008), as neurons reduce expression of the chloride accumulator, NKCC1 (Na-K-Cl cotransporter 1), in favor of the chloride extruder, KCC2 (K-Cl cotransporter 2), switching GABA A receptors from excitatory to inhibitory (Ehrlich et al, 2013). In adults, stress influences GABAergic transmission by regulating the balance NKCC1 and KCC2 expression (Maguire, 2014; Sarkar et al, 2011). Despite the stress sensitivity of these transporters and their role in neuronal maturation, it is unknown whether prenatal stress or escitalopram influences their expression in the developing amygdala.…”

Section: Introductionmentioning

confidence: 99%

Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

Ehrlich¹,

Neigh

Bourke³

et al. 2015

Neuropharmacology

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Depression during pregnancy has been linked to in utero stress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10-20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stress model of maternal depression to test the hypothesis that in utero antidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stress and antidepressant treatment on gene expression related to GABAergic and serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopram and mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in utero stress exposure, regardless of escitalopram treatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function. In contrast, prenatal escitalopram exposure alone elevated amygdala expression of 5-HT1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdala abated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stress causes age-dependent deficits in anxiety-like behavior and amygdala function in female offspring, regardless of antidepressant exposure.

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“…Loss of inhibitory GABAergic transmission is linked to marked glucocorticoid-dependent downregulation of the potassium-chloride co-transporter, KCC2, resulting in enhanced intracellular chloride ion concentration and a weakened membrane chloride gradient (59). Notably, chronic variable stress also causes downregulation of KCC2 in CRH neurons, consistent with lasting impairments in inhibitory GABA signaling (60). …”

Section: Cellular Impact Of Chronic Stress On Medial Parvocellular Pvmentioning

confidence: 96%

Paraventricular Hypothalamic Mechanisms of Chronic Stress Adaptation

2016

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The hypothalamic paraventricular nucleus (PVN) is the primary driver of hypothalamo–pituitary–adrenocortical (HPA) responses. At least part of the role of the PVN is managing the demands of chronic stress exposure. With repeated exposure to stress, hypophysiotrophic corticotropin-releasing hormone (CRH) neurons of the PVN display a remarkable cellular, synaptic, and connectional plasticity that serves to maximize the ability of the HPA axis to maintain response vigor and flexibility. At the cellular level, chronic stress enhances the production of CRH and its co-secretagogue arginine vasopressin and rearranges neurotransmitter receptor expression so as to maximize cellular excitability. There is also evidence to suggest that efficacy of local glucocorticoid feedback is reduced following chronic stress. At the level of the synapse, chronic stress enhances cellular excitability and reduces inhibitory tone. Finally, chronic stress causes a structural enhancement of excitatory innervation, increasing the density of glutamate and noradrenergic/adrenergic terminals on CRH neuronal cell somata and dendrites. Together, these neuroplastic changes favor the ability of the HPA axis to retain responsiveness even under conditions of considerable adversity. Thus, chronic stress appears able to drive PVN neurons via a number of convergent mechanisms, processes that may play a major role in HPA axis dysfunction seen in variety of stress-linked disease states.

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Stress-induced plasticity of GABAergic inhibition

Cited by 85 publications

References 81 publications

Simultaneous two-photon imaging of intracellular chloride concentration and pH in mouse pyramidal neurons in vivo

Simultaneous two-photon imaging of intracellular chloride concentration and pH in mouse pyramidal neurons in vivo

Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

Paraventricular Hypothalamic Mechanisms of Chronic Stress Adaptation

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