Fig. 5: Reduced dendritic feedforward inhibition of layer 2/3 dACC pyramidal neurons in response to electrical stimulation at layer 5 in PV-Lmo4KO mice.

a Diagram of the inhibitory circuits and placement of stimulation electrodes at layer 5 of the ACC. MDT, inputs from mediodorsal thalamic nucleus onto layer 2/3 pyramidal neurons that project onto pyramidal neurons in layer 5³³. Layer 5 stimulation activates mainly SST rather than PV interneurons³⁴. CC, cortical-cortical inputs. TC, inputs from other higher-order thalamic nuclei to the cortex, for example the ventral medial thalamus³³ and matrix thalamic nuclei³⁹. b Representative traces of monosynaptic EPSC and di-synaptic feedforward IPSC recorded in L2/3 pyramidal neurons of WT (black, n = 38 cells/14 mice) and KO (red, n = 13 cells/6 mice). Enlarged traces highlight short EPSC and long IPSC latencies, respectively. c E-I relationship plotted for individual cells reveals a subtractive shift for PV-Lmo4KO mice. Reduced IPSC inputs (d) and increased E/I ratio (e) in PV-Lmo4KO mice. f Latency of excitatory and inhibitory inputs to L2/3 pyramidal neurons of WT and KO mice evoked by electrical stimulation at layer 5. In KO, the IPSC showed (g) a decrease of PPR and (h) enhanced short-term depression. h Inset shows the mean of the ratio of 5th/1st IPSC or EPSC at various frequencies. Representative traces are shown above each graph (WT, black; KO red). n = 13 cells/5 WT, 11 cells/5 KO mice. *, **, ***, p < 0.05, 0.01, 0.001, respectively.