The schizophrenia- and autism-associated gene, transcription factor 4 regulates the columnar distribution of layer 2/3 prefrontal pyramidal neurons in an activity-dependent manner.

Disruption of the laminar and columnar organization of the brain is implicated in several psychiatric disorders. Here, we show in utero gain-of-function of the psychiatric risk gene transcription factor 4 (TCF4) severely disrupts the columnar organization of medial prefrontal cortex (mPFC) in a transcription- and activity-dependent manner. This morphological phenotype was rescued by co-expression of TCF4 plus calmodulin in a calcium-dependent manner and by dampening neuronal excitability through co-expression of an inwardly rectifying potassium channel (Kir2.1). For we believe the first time, we show that N-methyl-d-aspartate (NMDA) receptor-dependent Ca2+ transients are instructive to minicolumn organization because Crispr/Cas9-mediated mutation of NMDA receptors rescued TCF4-dependent morphological phenotypes. Furthermore, we demonstrate that the transcriptional regulation by the psychiatric risk gene TCF4 enhances NMDA receptor-dependent early network oscillations. Our novel findings indicate that TCF4-dependent transcription directs the proper formation of prefrontal cortical minicolumns by regulating the expression of genes involved in early spontaneous neuronal activity, and thus our results provides insights into potential pathophysiological mechanisms of TCF4-associated psychiatric disorders.

Relative pitch perception in the European starling (Sturnus vulgaris): further evidence for an elusive phenomenon.

Relative pitch perception in animals has been difficult to demonstrate. This failing is due in part to stimulus sets that make an absolute pitch solution viable. In Experiment 1, starlings failed to acquire a discrimination that could be solved only on the basis of relative pitch. In Experiment 2, starlings were trained on a smaller set of pitch patterns, for which both absolute and relative pitch solutions were available, then tested with three series of unreinforced probe stimuli. Series 1 assessed stimulus control by absolute pitch. In Series 2, absolute pitch cues dictated one response, and relative pitch cues dictated a different response. Results indicate that starlings extract relative pitch from artificial pitch patterns only after acquiring a discrimination that permits both absolute and relative pitch solutions. Results are discussed in terms of the relative salience of absolute and relative pitch.