Figure 1.

Schematic overview of major intralaminar circuits in layer 5 (L5). (A) Both the slender-tufted intratelencephalic (IT) cells (left) and thick-tufted pyramidal tract (PT) cells (right) form homotypic excitatory synaptic connections. IT cells additionally connect to PT cells, but PT cells connect to IT cells only very rarely. IT→IT and IT→PT connections both occur at a fairly high rate (Brown and Hestrin, 2009; Lefort et al., 2009; Kiritani et al., 2012). PT→PT connectivity occurs less frequently, but is structured into strongly interconnected subnetworks (Song et al., 2005; Perin et al., 2011). (B) Left: both IT and PT cells (red) excite parvalbumin (PV) cells (blue) and receive perisomatic inhibition from PV cells (Angulo et al., 2003; Silberberg and Markram, 2007; Kruglikov and Rudy, 2008). Right: somatostatin (SOM)/Martinotti cells (green) inhibit the distal dendrites of both PT and IT cells. These interneurons receive excitatory input from PT cells, but it is unknown if IT cells also excite them. (C) Experimental evidence for disynaptic inhibitory circuits between L5 pyramidal cells (PCs). Left: example traces showing two types of disynaptic inhibitory responses in a postsynaptic PC (red) driven by spiking in a presynaptic PC (black). Firing the presynaptic cell at 20 Hz (top traces) drives a transient, frequency-independent disynaptic inhibitory response (indicated by the blue arrow) which is likely mediated by activation of a PV/basket cell at the onset of spiking. Firing the same cell at 70 Hz (bottom traces) reveals a second, frequency-dependent form of disynaptic inhibition (indicated by the red arrow) which is likely due to delayed recruitment of a (SOM) Martinotti cell. Right: membrane potential responses of different interneurons to high-frequency stimulation of an L5 PC. Top: (PV) basket cells receive strong excitatory postsynaptic potentials (EPSPs) at the onset of stimulation, which can drive subthreshold (gray traces) or supra-threshold depolarization (blue traces). In either case, the postsynaptic response is initially strong, but then depresses rapidly. Bottom: EPSPs in Martinotti cells are weak and unreliable at the onset of L5 PC firing, but these facilitate and can eventually drive postsynaptic spiking, leading to frequency dependent disynaptic inhibition (FDDI; gray traces, subthreshold responses, red traces- suprathreshold responses). Reproduced with permission from Silberberg and Markram (2007). (D) Schematic of interneuron-to-interneuron connectivity in L5. PV cells (blue) form reciprocal chemical and electrical synapses with other PV cells. SOM cells are electrically but not chemically connected to other SOM cells, and form chemical synapses onto PV cells and vasoactive intestinal peptide (VIP) cells. VIP cells inhibit PV cells and SOM cells. Dashed lines indicate two weaker outputs from PV cells onto SOM cells and VIP cells.