Context-dependent and dynamic functional influence of corticothalamic pathways to first- and higher-order visual thalamus

Abstract

Layer 6 (L6) is the sole purveyor of corticothalamic (CT) feedback to first-order thalamus and also sends projections to higher-order thalamus, yet how it engages the full corticothalamic circuit to contribute to sensory processing in an awake animal remains unknown. We sought to elucidate the functional impact of L6CT projections from the primary visual cortex to the dorsolateral geniculate nucleus (first-order) and pulvinar (higher-order) using optogenetics and extracellular electrophysiology in awake mice. While sustained L6CT photostimulation suppresses activity in both visual thalamic nuclei in vivo, moderate-frequency (10 Hz) stimulation powerfully facilitates thalamic spiking. We show that each stimulation paradigm differentially influences the balance between monosynaptic excitatory and disynaptic inhibitory corticothalamic pathways to the dorsolateral geniculate nucleus and pulvinar, as well as the prevalence of burst versus tonic firing. Altogether, our results support a model in which L6CTs modulate first- and higher-order thalamus through parallel excitatory and inhibitory pathways that are highly dynamic and context-dependent.

A Closer Look at Corticothalamic “Loops”

“…A defining feature of primary sensory cortical areas has been that they receive and reciprocate thalamic “relays” of external events. The interactions of sensory input, autonomous cortical processes, and more cognitive functions, however, remain under active investigation; and continuing work is bringing into better focus the fuller spatial, temporal, and dynamic complexity of the cortical-subcortical sensory pathways, conveniently described as “loops.” There are reports that corticothalamic (CT) connections regulate the mode of thalamic activity and can exert a flexible control of thalamocortical (TC) inputs (mouse cortex: Mease et al, 2014 ; Crandall et al, 2015 ; Guo et al, 2017 ; Kirchgessner et al, 2020 ). Auditory CT feedback to the medial geniculate body is found to contribute to the detection of harmonicity, an important grouping cue in the perception of complex sounds (ferrets: Homma et al, 2017 ).…”

Long-range GABAergic projections contribute to cortical feedback control of sensory processing

“…In the OB, stimulating cortical glutamatergic projections yields optimal inhibition of MCs and TCs in the beta range (20-40Hz) and decreases with faster stimulation regimes 39 . Similar frequency-dependent activity also takes place in lower-order thalamic nuclei: low-frequency cortico-thalamic axon stimulation suppresses thalamic activity while high-frequency stimulation enhances it 89, 90 . In both systems, GABAergic relay neurons seem to implement band-pass filtering of the cortical glutamatergic drive.…”

Identification of retinal ganglion cell types and brain nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock‐in allele

“…It is best revealed in coronal sections from CAG:Dre; Brn3c CKOCre ; Rosa26 AP and Brn3c Cre ; Brn3a CKOAP mice, but it is also clearly seen in Rax:Cre; Brn3c CKOAP mice, demonstrating that it is originating from retinal projections (since only RGCs are labeled in these mice). The TRN is a sheet-like structure containing mostly GABA-ergic neurons that receives collaterals from both talamocortical and corticothalamic projections of adjacent thalamic nuclei and their cortical target areas and provides in turn inhibition to the neighboring thalamic nuclei (Coleman & Mitrofanis, 1996;Crick, 1984;Jones, 1975 -Perez et al, 2017;Kirchgessner, Franklin, & Callaway, 2020). Previous reports of RGC input to the TRN are rare (Matteau, Boire, & Ptito, 2003), and this is to our knowledge, the first report of such input in mice.…”

“…The thalamic reticular nucleus (TRN) is a sheetlike structure containing mostly GABA-ergic neurons that receives collaterals from both thalamocortical and corticothalamic projections of adjacent thalamic nuclei and their cortical target areas and provides in turn inhibition to the neighboring thalamic nuclei (Coleman & Mitrofanis, 1996;Crick, 1984;Jones, 1975). The visual TRN is directly apposed to the LGN and OPT, receives significant input from LGN, LPTN and layer 6 pyramidal neurons of V1 and exercises inhibitory feedback to the dLGN and vLGN (Clemente-Perez et al, 2017;Kirchgessner, Franklin, & Callaway, 2020). Previous reports of RGC input to the TRN are rare (Matteau, Boire, & Ptito, 2003), and this is to our knowledge the first report of such input in mice.…”