Cell Class-Dependent Intracortical Connectivity and Output Dynamics of Layer 6 Projection Neurons of the Rat Primary Visual Cortex

Abstract

Neocortical information processing is powerfully influenced by the activity of layer 6 projection neurons through control of local intracortical and subcortical circuitry. Morphologically distinct classes of layer 6 projection neuron have been identified in the mammalian visual cortex, which exhibit contrasting receptive field properties, but little information is available on their functional specificity. To address this we combined anatomical tracing techniques with high-resolution patch-clamp recording to identify morphological and functional distinct classes of layer 6 projection neurons in the rat primary visual cortex, which innervated separable subcortical territories. Multisite whole-cell recordings in brain slices revealed that corticoclaustral and corticothalamic layer 6 projection neurons exhibited similar somatically recorded electrophysiological properties. These classes of layer 6 projection neurons were sparsely and reciprocally synaptically interconnected, but could be differentiated by cell-class, but not target-cell-dependent rules of use-dependent depression and facilitation of unitary excitatory synaptic output. Corticoclaustral and corticothalamic layer 6 projection neurons were differentially innervated by columnar excitatory circuitry, with corticoclaustral, but not corticothalamic, neurons powerfully driven by layer 4 pyramidal neurons, and long-range pathways conveyed in neocortical layer 1. Our results therefore reveal projection target-specific, functionally distinct, streams of layer 6 output in the rodent neocortex.

The Synaptic Organization of Layer 6 Circuits Reveals Inhibition as a Major Output of a Neocortical Sublamina

“…First, rather than L6 CThNs preferentially synapsing onto INH INs (Thomson, 2010;West et al, 2006), VPM/POm L6 L CThNs synapsed onto L6 L PV INs at about half the frequency of L6 L CCNs. Second, VPM/POm L6 L CThN/L6 L PV synapses depressed, an unexpected finding as facilitating synapses are considered a signature of L6 CThNs synapses (Beierlein and Connors, 2002;Cotel et al, 2018;Crandall et al, 2015;Deschênes and Hu, 1990;Ferster and Lindströ m, 1985;Jackman et al, 2016;Reichova and Sherman, 2004;Stratford et al, 1996;Turner and Salt, 1998;West et al, 2006). These results indicate that some key assumptions regarding the synaptic connectivity of L6 neurons do not hold in either L6 U or L6 L .…”

“…Unlike excitatory neurons in other cortical layers, excitatory projection neurons (PNs) in L6, one of the least-well-understood cortical layers (Briggs, 2010;Thomson, 2010), are notable for infrequently synapsing onto other PNs (Beierlein and Connors, 2002;Beierlein et al, 2003;Cotel et al, 2018;Crandall et al, 2017;Lee and Sherman, 2009;Lefort et al, 2009;Mercer et al, 2005;Schubert et al, 2003;Seeman et al, 2018;Tarczy-Hornoch et al, 1999;West et al, 2006). L6 also contains inhibitory interneurons (INH INs), about half of which express parvalbumin (PV) (Lee et al, 2010;Perrenoud et al, 2013), typical of fast-spiking (FS) INH INs.…”

Neuromodulation, Short-Term and Long-Term Plasticity in Corticothalamic and Hippocampal Neuronal Networks

“…CCL neurons are often described to have a tall morphology, meaning that their apical dendrites reach layer 1 and terminate with a small tuft. Along the way to layer 1 a few branches from the apical dendrite terminates in layers 4 and 2/3 (Katz 1987, Mercer et al 2005, Cotel et al 2018. The CCL neurons are rarer than both CT and CC neurons.…”

“…Compared to CCL neurons CT neurons can be depicted to be short pyramidal neurons, i.e. they have dendritic arbors terminating in layer 4 with an extensive tuft (Katz 1987, Brumberg et al 2003, Mercer et al 2005, Kumar and Ohana 2008, Cotel et al 2018. CCL and CT neurons fire action potentials in a similar pattern when stimulated with a square depolarizing current pulse, and they cannot be differentiated based on their intrinsic pattern of electrical activity (Mercer et al 2005, Cotel et al 2018.…”

“…they have dendritic arbors terminating in layer 4 with an extensive tuft (Katz 1987, Brumberg et al 2003, Mercer et al 2005, Kumar and Ohana 2008, Cotel et al 2018. CCL and CT neurons fire action potentials in a similar pattern when stimulated with a square depolarizing current pulse, and they cannot be differentiated based on their intrinsic pattern of electrical activity (Mercer et al 2005, Cotel et al 2018. Both CCL and CT neurons fire action potentials regularly throughout a current step and classify as regular firing neurons (Mercer et al 2005, Crandall et al 2017, Cotel et al 2018.…”