Functional Organization of the Somatosensory Cortical Layer 6 Feedback to the Thalamus

Abstract

The pathway from cortical layer 6 to the thalamus is a property of all thalamic relay nuclei. This pathway, as a population, directly excites relay cells and indirectly inhibits them via the thalamic reticular nucleus. To understand the circuit organization of this cortical feedback, we used laser-scanning photostimulation, which specifically activates somata or dendrites, to stimulate the primary somatosensory cortex in an in vitro thalamocortical slice preparation while recording from neurons of the ventral posterior medial nucleus. Layer 6 photostimulation evoked biphasic excitatory postsynaptic current/inhibitory postsynaptic current (EPSC/IPSC) responses in the neurons of the ventral posterior medial nucleus, indicating that such photostimulation strongly activates reticular cells. These disynaptic IPSCs were greatly suppressed or abolished by bath application of the muscarinic agonist acetyl-beta-methylcholine. Our results suggest that the top-down modulation of thalamic neurons from cortical layer 6 involves an inhibitory component via the thalamic reticular nucleus, and this component can be selectively reduced by cholinergic input. Finally, we found the footprints for the excitatory corticothalamic and the inhibitory cortico-reticulo-thalamic inputs to be located in similar positions, though in some cases they are offset. Both patterns have implications for cortico-reticulo-thalamic circuitry.

Cortical control of adaptation and sensory relay mode in the thalamus

“…In summary, L6 responses in the VPM combined inhibition and excitation, which were variable across the population, as also demonstrated in vitro (26). The balance between excitation and inhibition changed in a time-sensitive manner to favor excitation.…”

“…The L6-induced depolarization shown above and in previous in vitro studies (19,26) provides a cellular mechanism for changes in firing mode. Thalamic depolarization via the L6 cortico-thalamic pathway may serve to inactivate the T-type Ca 2+ channels and thereby weaken intrinsic bursting (17,28).…”

“…While L6 excites VPM neurons monosynaptically, the inhibition most likely results from the coactivation of the GABAergic TRN (26). The resulting IPSPs were transient during longer L6 activation (>200 ms, Fig.…”

Local Connections of Excitatory Neurons to Corticothalamic Neurons in the Rat Barrel Cortex

“…These results illustrate which excitatory neurons of the S1 cortical column send information through L6 CTNs to the thalamic compartment corresponding to the column. Strong local excitatory inputs to L6 CTNs from their own layer were found in previous studies using laser-scanning photostimulation by glutamate uncaging (Zarrinpar and Callaway, 2006;Llano and Sherman, 2009;Lam and Sherman, 2010;Hooks et al, 2011). Because photostimulation with a resolution of 50 -75 m probably would activate several CTNs simultaneously (Hooks et al, 2011), large EPSPs might be evoked in the recorded neuron through dense nearby connections between CTNs.…”

“…In this reciprocal circuit, L6 corticothalamic projection neurons (CTNs) are considered to enhance and tune thalamic responses to peripheral stimuli (Yuan et al, 1986;Yan and Suga, 1996;Przybyszewski et al, 2000;Alitto and Usrey, 2003;Temereanca and Simons, 2004;Thomson, 2010). Local connections between cortical layers are well developed (Briggs and Callaway, 2001;Mercer et al, 2005;Zarrinpar and Callaway, 2006;West et al, 2006;Lefort et al, 2009;Llano and Sherman, 2009;Lam and Sherman, 2010;Hooks et al, 2011), and in addition to external inputs, local translaminar inputs are involved in shaping CTN activity. Therefore, the laminar organization of local excitatory inputs to CTNs may be important for cortical modulation of thalamic activity.…”