Journal: eLife

Article Title: Disrupted-in-schizophrenia-1 is required for normal pyramidal cell–interneuron communication and assembly dynamics in the prefrontal cortex

doi: 10.7554/elife.79471

Figure Lengend Snippet: Figure 1. Reduced interneuron (INT) activity in the medial prefrontal cortex (mPFC) of Disc1-mutant mice. (a) Schematic of the recording configuration. Silicon probes or tetrode microdrives were targeted to the mPFC of freely moving mice. Bottom: identification of pyramidal cells (PYRs, black) and INTs (blue) based on duration (a) and asymmetry index (b – c)/(b + c) of filtered action potential waveforms. Red dots show optogenetically identified parvalbumin-positive interneurons (PVIs, see d–g). Blue and gray insets show an average unfiltered spike of an INT and PYR, respectively. (b) Example raster plots of PYR and INT activity in a freely moving control (black) and Disc1-mutant mouse (green). Each line shows the time series of spikes of a single neuron. (c) Decreased spike rates of INTs (Mann–Whitney U-test) but not PYRs (unpaired t-test) in the Disc1-mutant mPFC. Data points show averages of individual mice. (d) Schematic of the experimental strategy to label PVIs with ChR2. (e) Optogenetic identification of PVIs during blue laser illumination in awake head-fixed mice. Top: 0.3–6 kHz-filtered recording of one channel of the silicon probe (a single channel is shown for clarity). Bars indicate spike times of the unit. (f) Comparable average waveforms of light-triggered and spontaneous spikes of PVIs in both control (left) and Disc1- mutant mice (right). (g) Reduced spontaneous spiking of optogenetically identified PVIs in head-fixed PV-Cre-Disc1-mutant animals (Mann–Whitney U-test). Data points are individual PVIs. Boxes show median and upper/lower quartiles of the data distribution, *p<0.05.

Article Snippet: AAV1- flex- ChR2- Tdtomato (Addgene, titer 2 * 1012/ml, 0.5 μl) or AAV1- flex- ChR2- mCherry (Charite Vector core, titer 4 * 1011/ml, 0.5 μl) was slowly infused into the right or left mPFC at two anterioposterior locations (1.5 and 2 mm anterior from bregma) using thin glass pipettes fabricated with a microfilament puller (Flaming Brown).

Techniques: Activity Assay, Mutagenesis, Control, MANN-WHITNEY