A novel layer4 corticofugal cell type/projection involved in thalamo-cortico-striatal sensory processing

In sensory cortices, the information flow has been thought to be processed vertically across cortical layers, with layer 4 being the major thalamo-recipient one which relays thalamic signals to layer 2/3, which in turn transmit thalamic information to layer 5 and 6 to then leave the cortex to reach subcortical and cortical long-range structures. Although several exceptions to this model have been described, neurons in layer 4 are still considered to establish only local (i.e., inter-laminar and short-range) connections. Here, taking advantage of anatomical, electrophysiological, optogenetic techniques, we describe for the first time a long-range corticostriatal class of pyramidal neurons in layer 4 (CS-L4) of the mouse auditory cortex that receive direct thalamic inputs. The CS-L4 neurons are embedded in a feedforward inhibitory circuit involving local parvalbumin neurons and establish connections in the posterior striatum in yet another feedforward inhibitory thalamo -> cortico(L4)-> striatal circuit to potentially contribute to control the output of striatal spiny projection neurons. Significance statement The assumption has been that layer 4 neurons are the main thalamic recipient layer, projecting to the upper cortical layer 2/3. However, no study has revealed a detailed understanding of the circuit mechanisms by which layer 4 sends a projection in a subcortical structure such as the striatum and differentially innervate the SPNs and intrastriatal Parv-expressing neurons. For the first time, our results demonstrate that the auditory cortex projects to the posterior part of the dorsal striatum via pyramidal neurons located in layer 4 (CS-L4 neurons). Here we propose a new wiring diagram that implemented the old one, in which layer 4 is not only involved in the transfer of thalamic input to the upper layer 2/3 but can exert a direct top-down control, bypassing intracortical processing, of subcortical structure such as the posterior part of the dorsal striatum posing a new conceptual cell element (CS-L4 neurons) for experimental and theoretical work of the cortical function.

Automated summary

This study reveals the existence of a long-range class of pyramidal neurons (CS-L4 neurons) in layer 4 of the mouse auditory cortex that receive direct thalamic inputs and establish connections with local parvalbumin neurons, contributing to a feedforward inhibitory circuit in the posterior striatum.