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2012 | 72 | 2 |

Tytuł artykułu

GABA, a neurotransmitter crucial for the development of neuronal circuits: involvement in autism spectrum disorders

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EN

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EN
The construction of the brain relies on genetic and environmental factors “nature and nurture”. While nature provides a set of genes that control the general organization of the brain, nurture ensures that genetically built neuronal circuits adapt to the environment. Learning constitutes an adaptive process involving activity-dependent mechanisms regulating several developmental steps, including synapses formation and elimination. One of the main actors in these processes is the neurotransmitter GABA, which inhibits adult neurons but depolarizes and excites immature ones because of high intracellular chloride concentration. In synergy with glutamate GABA gives rise to coherent network oscillations which are instrumental in enhancing synaptic efficacy at emerging glutamatergic and GABAergic pathways. A premature shift of GABA from the depolarizing to the hyperpolarizing direction severely impairs the morphological maturation of cortical cells. In addition, a dysfunction of GABAergic signaling early in postnatal development leads to an excitatory/inhibitory unbalance a condition that may account for some of the behavioral deficits observed in neuro-developmental disorders such as Autism Spectrum Disorders (ASD). ASD comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, marked impairment in verbal and non-verbal communication, social skills and cognition. Interestingly, in a small number of cases, ASD are associated with single mutations in genes involved in synaptic transmission, including single mutations of genes encoding for synaptic cell adhesion molecules of the Neurexin-Neuroligin families and for Shank3. Although rare, these mutations provide crucial information on the synaptic abnormalities which possibly affect ASD patients and point to synapses dysfunction as a possible site of autism origin.

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72

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2

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p.197

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  • Neurobiology Department, International School for Advanced Studies (SISSA), Trieste, Italy

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Bibliografia

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