Unknown

Dataset Information

0

Transcriptional signatures of cellular plasticity in mice lacking the alpha1 subunit of GABAA receptors.


ABSTRACT: GABAA receptors mediate the majority of inhibitory neurotransmission in the CNS. Genetic deletion of the alpha1 subunit of GABAA receptors results in a loss of alpha1-mediated fast inhibitory currents and a marked reduction in density of GABAA receptors. A grossly normal phenotype of alpha1-deficient mice suggests the presence of neuronal adaptation to these drastic changes at the GABA synapse. We used cDNA microarrays to identify transcriptional fingerprints of cellular plasticity in response to altered GABAergic inhibition in the cerebral cortex and cerebellum of alpha1 mutants. In silico analysis of 982 mutation-regulated transcripts highlighted genes and functional groups involved in regulation of neuronal excitability and synaptic transmission, suggesting an adaptive response of the brain to an altered inhibitory tone. Public gene expression databases permitted identification of subsets of transcripts enriched in excitatory and inhibitory neurons as well as some glial cells, providing evidence for cellular plasticity in individual cell types. Additional analysis linked some transcriptional changes to cellular phenotypes observed in the knock-out mice and suggested several genes, such as the early growth response 1 (Egr1), small GTP binding protein Rac1 (Rac1), neurogranin (Nrgn), sodium channel beta4 subunit (Scn4b), and potassium voltage-gated Kv4.2 channel (Kcnd2) as cell type-specific markers of neuronal plasticity. Furthermore, transcriptional activation of genes enriched in Bergman glia suggests an active role of these astrocytes in synaptic plasticity. Overall, our results suggest that the loss of alpha1-mediated fast inhibition produces diverse transcriptional responses that act to regulate neuronal excitability of individual neurons and stabilize neuronal networks, which may account for the lack of severe abnormalities in alpha1 null mutants.

SUBMITTER: Ponomarev I 

PROVIDER: S-EPMC1894896 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC2804419 | biostudies-literature
| S-EPMC7218123 | biostudies-literature
| S-EPMC3418418 | biostudies-literature
| S-EPMC2882199 | biostudies-literature
| S-EPMC2253290 | biostudies-literature
| S-EPMC2911342 | biostudies-literature
| S-EPMC2905594 | biostudies-literature
| S-EPMC4421780 | biostudies-literature
| S-EPMC4950669 | biostudies-literature
| S-EPMC5929507 | biostudies-literature