Brain Plasticity and Disease: A Matter of Inhibition

Baroncelli, Laura; Braschi, Mariachiara; Spolidoro, Maria; Begenisic, Tatjana; Maffei, Lamberto; Sale, Alessandro

doi:10.1155/2011/286073

Cited by 135 publications

(93 citation statements)

References 133 publications

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“…The balance between excitation and inhibition has been proven to be necessary to preserve a normal physiological function in the central nervous system (7,8). GABA, specifically, plays a pivotal role in the maintenance of this balance, as it is the major inhibitory neurotransmitter in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…GABAergic inhibition has been indicated to be important in normal physiological function within the brain. Alterations in this system (i.e., less inhibition) are shown to cause neurological disorders, such as epilepsy and autism (7,8). In addition to its classical inhibitory function within the SCN network, GABA has more recently been shown to also act as an excitatory transmitter, although its exact role is uncertain (4,(9)(10)(11)(12)(13).…”

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confidence: 99%

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Seasonal induction of GABAergic excitation in the central mammalian clock

Farajnia

Westering

Meijer

et al. 2014

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

107

129

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The balance between excitation and inhibition is essential for the proper function of neuronal networks in the brain. The inhibitory neurotransmitter γ-aminobutyric acid (GABA) contributes to the network dynamics within the suprachiasmatic nucleus (SCN), which is involved in seasonal encoding. We investigated GABAergic activity and observed mainly inhibitory action in SCN neurons of mice exposed to a short-day photoperiod. Remarkably, the GABAergic activity in a long-day photoperiod shifts from inhibition toward excitation. The mechanistic basis for this appears to be a change in the equilibrium potential of GABA-evoked current. These results emphasize that environmental conditions can have substantial effects on the function of a key neurotransmitter in the central nervous system.S easonal changes in the photoperiod of the Earth's temperate zones affect the behavior and physiology of many organisms (1). The central circadian clock, located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, can adapt to changes in day length and displays a compressed circadian pattern of electrical activity in short winter days and a decompressed pattern in long summer days (2). This pattern is based on a change in the phase distribution of the activity patterns of individual neurons, which becomes broad in the summer and narrow in the winter (3). The mechanisms that mediate and regulate photoperiod-induced phase distributions are currently not known.The neurotransmitter γ-aminobutyric acid (GABA) is believed to be involved in the phase adjustment and synchronization of the SCN neuronal network (4, 5). GABA and its receptors are expressed in most SCN neurons (6). GABAergic inhibition has been indicated to be important in normal physiological function within the brain. Alterations in this system (i.e., less inhibition) are shown to cause neurological disorders, such as epilepsy and autism (7,8). In addition to its classical inhibitory function within the SCN network, GABA has more recently been shown to also act as an excitatory transmitter, although its exact role is uncertain (4, 9-13). To understand the influence of photoperiod on GABAergic function, we studied synaptic activity, using patch clamp, and GABAergic responses, using Ca 2+ imaging techniques, in the SCN of mice adjusted to long-day and short-day photoperiods. We hypothesized that the narrow, synchronized phase distribution of active neurons during short-day photoperiods would result in increased synaptic activity during the day. Surprisingly, however, exposure to a short-day photoperiod decreased the frequency of spontaneous GABAergic synaptic events compared with the long-day photoperiod.Subsequently, we tested the effect of photoperiod on GABAinduced excitation in the SCN neuronal network. Ca 2+ transients were measured in response to GABA stimulation in long-day and short-day photoperiods. Interestingly, of all cells from the long-day photoperiod, 40% were excitatory and 36% were inhibitory. In contrast, in the short-day photoperiod, 28% of the c...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Seasonal induction of GABAergic excitation in the central mammalian clock

Farajnia

Westering

Meijer

et al. 2014

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

107

129

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“…The rationale for the application of a-tDCS to amblyopia is based on previous work showing that a-tDCS reduces gamma-aminobutyric acidmediated inhibition [28][29][30], a key mechanism underlying suppression of the amblyopic eye [3,57]. A reduction in inhibition may also enhance the potential for experience dependant plasticity [15,29,62,63]. It is possible that a-tDCS further reduced suppression of the amblyopic eye, therefore enhancing the effects of dichoptic treatment on stereopsis, which requires precise binocular integration.…”

Section: Discussionmentioning

confidence: 99%

Transcranial Direct Current Stimulation Enhances Recovery of Stereopsis in Adults With Amblyopia

et al. 2013

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Amblyopia is a neurodevelopmental disorder of vision caused by abnormal visual experience during early childhood that is often considered to be untreatable in adulthood. Recently, it has been shown that a novel dichoptic videogamebased treatment for amblyopia can improve visual function in adult patients, at least in part, by reducing inhibition of inputs from the amblyopic eye to the visual cortex. Non-invasive anodal transcranial direct current stimulation has been shown to reduce the activity of inhibitory cortical interneurons when applied to the primary motor or visual cortex. In this doubleblind, sham-controlled cross-over study we tested the hypothesis that anodal transcranial direct current stimulation of the visual cortex would enhance the therapeutic effects of dichoptic videogame-based treatment. A homogeneous group of 16 young adults (mean age 22.1±1.1 years) with amblyopia were studied to compare the effect of dichoptic treatment alone and dichoptic treatment combined with visual cortex direct current stimulation on measures of binocular (stereopsis) and monocular (visual acuity) visual function. The combined treatment led to greater improvements in stereoacuity than dichoptic treatment alone, indicating that direct current stimulation of the visual cortex boosts the efficacy of dichoptic videogamebased treatment. This intervention warrants further evaluation as a novel therapeutic approach for adults with amblyopia.

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“…Moreover, the beneficial effects elicited by EE were totally counteracted by intracortical infusion of the benzodiazepine Diazepam, revealing a key role for decreased GABAergic transmission in driving amblyopia rescue in enriched animals. This was one of the first demonstrations that reducing the inhibition-excitation balance reinstates plasticity in the adult brain [103], as subsequently confirmed by another study in which a pharmacological reduction of inhibition through intracortical infusion of either MPA (an inhibitor of GABA synthesis) or picrotoxin (a GABAA antagonist) was reported to reactivate plasticity in response to MD in adult rats [104] (Figure 3). Figure 3.…”

Section: Amblyopia Recovery In Enriched Animalsmentioning

confidence: 60%