A Corticothalamic Circuit for Refining Tactile Encoding

Abstract

A fundamental task for the brain is to determine which aspects of the continuous flow of information is the most relevant in a given behavioral situation. The information flow is regulated via dynamic interactions between feedforward and feedback pathways. One such pathway is via corticothalamic feedback. Layer 6 (L6) corticothalamic (CT) cells make both cortical and thalamic connections and, therefore, are key modulators of activity in both areas. The functional properties of L6 CT cells in sensory processing were investigated in the mouse whisker system. Optogenetic activation of L6 CT neurons decreased spontaneous spiking, with the net effect that a whisker-evoked response was more accurately detected (larger evoked-to-spontaneous spiking ratio) but at the expense of reducing the response probability. In addition, L6 CT activation decreases sensory adaptation in both the thalamus and cortex. L6 CT activity can thus tune the tactile system, depending on the behaviorally relevant tactile input.

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

“…However, VPM-only L6 U CThN/L6 U IL-PV synapses facilitated while L6 U CCN/L6 U IL-PV synapses depressed, suggesting that L6 U IL-PV INs will be influenced by the specific patterns of presynaptic activity as well as the distinct response profiles of L6 U VPM-only CThNs and CCNs Vé lez-Fort et al, 2014). L6 PNs are reported to have very low spike rates in the barrel cortex and other sensory cortices, which is consistent with their relatively weak TC input as compared to PV INs, although higher firing rates have been reported (Kwegyir-Afful and Simons, 2009;Landry and Dykes, 1985;Lee et al, 2008;Niell and Stryker, 2008;O'Connor et al, 2010;Pauzin and Krieger, 2018;Vé lez-Fort et al, 2014). Under low-firing rate conditions, L6 U CCN/IL-PV synapses would escape depression and may be favored, while L6 U CThN input would remain unenhanced by facilitation.…”

“…Since Cre recombinase is expressed in both VPM-only and VPM/POm L6 CThNs in Ntsr1-Cre mice (Chevé e et al, 2018), using this line to modulate the activity of L6 CThNs in vitro and in vivo likely engages the circuits of both L6 U and L6 L , although perhaps to different degrees Guo et al, 2017;Kim et al, 2014;Olsen et al, 2012;Pauzin and Krieger, 2018;Williamson and Polley, 2019). Thus, disambiguating contributions from the two L6a sublayers to sensory processing using Ntsr1-Cre mice is challenging Crandall et al, 2017;Guo et al, 2017;Olsen et al, 2012;Pauzin and Krieger, 2018;Williamson and Polley, 2019), although the circuit organization we show here suggests that the two sublayers have distinct functions. VPM-only L6 U CThNs project to L4, the main thalamorecipient layer, and activate IL-PV INs, which also receive strong TC input, suggesting that L6 U is involved in gain control and the modulation of cortical activity in response to sensory input Mease et al, 2014;Olsen et al, 2012;Pauzin and Krieger, 2018).…”

“…Prior studies of the local synaptic organization of L6 indicate that INH INs preferentially receive input from L6 CThNs relative to L6 CCNs (Thomson, 2010;West et al, 2006). Furthermore, optogenetic activation of L6 CThNs enhances the activity of IL-PV and local PV INs Guo et al, 2017;Olsen et al, 2012;Pauzin and Krieger, 2018). We tested whether L6 U PV INs exhibit a privileged relation with L6 CThNs by comparing the synaptic connections of L6 CThNs and L6 CCNs onto PV INs using paired whole-cell recordings.…”

“…Most cortical inhibition is generated locally within a layer (Dantzker and Callaway, 2000;Feldmeyer et al, 2018;Kä tzel et al, 2011). However, it has become increasingly clear that inhibitory effects between layers affect the cortical response, only some of which are mediated by classic sources of interlaminar inhibition: dendrite-targeting somatostatin inhibitory neurons and the subset of layer 1 (L1) inhibitory neurons that send axons into the deeper layers Guo et al, 2017;Kapfer et al, 2007;Kä tzel et al, 2011;Muñ oz et al, 2017;Naka et al, 2019;Olsen et al, 2012;Pauzin and Krieger, 2018;Pluta et al, 2015;Schuman et al, 2019;Silberberg and Markram, 2007;Xu et al, 2016).…”

“…L6 INH INs are thought to receive preferential input from L6 corticothalamic neurons (CThNs), one of the two major types of L6 PNs (West et al, 2006). This privileged relation is hypothesized to contribute to the modulation of the cortical response to sensory input by L6 CThNs, generating the broad cortical inhibition following the activation of L6 CThNs in vivo mediated by local and interlaminar projections of PV INs Guo et al, 2017;Kim et al, 2014;Olsen et al, 2012;Pauzin and Krieger, 2018;Williamson and Polley, 2019), and is thought to distinguish L6 CThNs from the other major class of L6 PNs, L6 corticocortical neurons (CCNs) (Thomson, 2010).…”