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Urban-Ciecko, J.

Publications and source records attributed to Urban-Ciecko, J..

2 recordsLinked to original sources

β-catenin signaling via astrocyte-encoded TCF7L2 regulates neuronal excitability and social behavior

Astrocytes play essential roles in supporting neuronal activity and synapse formation; however, mechanisms by which these functions are regulated are unclear. The Wnt/{beta}-catenin signaling pathway plays a crucial role in brain development and is implicated in neurodevelopmental disorders including autism spectrum disorder (ASD). We sought to investigate if some impacts of Wnt signaling are mediated via astrocytes. Here we show that the canonical Wnt/{beta}-catenin pathway is active in postnatal cortical astrocytes and that its effector, the transcription factor TCF7L2 -is expressed in astrocyte lineage cells during embryonic and postnatal development in both mouse and human. Astrocyte-specific deletion of Tcf7l2 in the early postnatal period led to alterations in astrocyte morphology, membrane depolarization and decreased cortical neuron excitability. Mice with the conditional knockout exhibited increased sociability and social preference in a naturalistic setting. Taken together, these data reveal a key role of astrocytic Wnt signaling in shaping postnatal neuronal development and adult social behavior.

neuroscience

Learning-induced plasticity in the barrel cortex is disrupted by inhibition of layer 4 somatostatin-containing interneurons

Learning-related plasticity in the cerebral cortex is linked to the action of disinhibitory circuits of interneurons. Pavlovian conditioning, in which stimulation of the vibrissae is used as conditioned stimulus, induces plastic enlargement of the cortical functional representation of vibrissae activated during conditioning, visualized with [14C]-2-deoxyglucose (2DG). Using layer-specific, cell-selective DREADD transductions, we examined the involvement of somatostatin- (SOM-INs) and vasoactive intestinal peptide (VIP-INs)-containing interneurons in the development of learning-related plastic changes. We injected DREADD-expressing vectors into layer IV (L4) barrels or layer II/III (L2/3) areas corresponding to activated vibrissae. The activity of interneurons was modulated during training, and 2DG maps were obtained 24 h later. In mice with L4 but not L2/3 SOM-INs suppressed during conditioning, the plastic change of whisker representation and the conditioned reaction were absent. No effect of inhibiting VIP-INs was found. We report that the activity of L4 SOM-INs is indispensable for learning-induced plastic change.

neuroscience