Organization of Cortical and Thalamic Input to Pyramidal Neurons in Mouse Motor Cortex

Abstract

Determining how long-range synaptic inputs engage pyramidal neurons in primary motor cortex (M1) is important for understanding circuit mechanisms involved in regulating movement. We used channelrhodopsin-2 (ChR2)-assisted circuit mapping to characterize the long-range excitatory synaptic connections made by multiple cortical and thalamic areas onto pyramidal neurons in mouse vibrissal motor cortex (vM1). Each projection innervated vM1 pyramidal neurons with a unique laminar profile. Collectively, the profiles for different sources of input partially overlapped and spanned all cortical layers. Specifically, orbital cortex (OC) inputs primarily targeted neurons in L6. Secondary motor cortex (M2) inputs excited neurons mainly in L5B, including pyramidal tract (PT-type) neurons. In contrast, thalamocortical inputs from anterior motor-related thalamic regions, including VA/VL, targeted neurons in L2/3 through L5B, but avoided L6. Inputs from posterior sensory-related thalamic areas, including POm, targeted neurons only in the upper layers (L2/3 and L5A), similar to inputs from somatosensory (barrel) cortex. Our results show that long-range excitatory inputs target vM1 pyramidal neurons in a layer-specific manner. Inputs from sensory-related cortical and thalamic areas preferentially target the upper-layer pyramidal neurons in vM1. In contrast, inputs from OC and M2, areas associated with volitional and cognitive aspects of movements, bypass local circuitry and have direct monosynaptic access to neurons projecting to brainstem and thalamus.

Neural mechanisms of transient neocortical beta rhythms: Converging evidence from humans, computational modeling, monkeys, and mice

“…cortex (55), which could be a single source of both drives. In motor cortex, two distinct thalamocortical projection pathways to primary motor cortex in proximal and distal projection patterns have been shown to emerge from distinct thalamic zones (55,56).…”

Learning in the Rodent Motor Cortex

“…One emerging principle from these experiments is lamina-specific connectivity, which has great functional implications. On the input side, for example, it has been found that basal ganglia–recipient and cerebellum-recipient nuclei of the thalamus project asymmetrically to the motor cortex, with the former projecting predominantly to layer 1 apical dendrites of layer 2/3 and layer 5 neurons, whereas the latter projects directly to layer 2/3 and, to a lesser extent, to layer 5 (Hooks et al 2013; Kuramoto et al 2009, 2013). The differential projection patterns of these two thalamic recipient zones suggest that information from the basal ganglia and cerebellum may take different routes through the motor cortex and partake in different types of computation.…”

“…Inputs from other cortical areas also arrive with characteristic laminar profiles. For example, somatosensory areas primarily drive layers 2/3 and 5a (Mao et al 2011), whereas frontal areas are biased toward contacting layers 5 and 6 (Hira et al 2013b, Hooks et al 2013, Rouiller et al 1993). Within the motor cortex, the predominant flow of information travels from superficial to deep layers (Weiler et al 2008).…”

“…These patterns of connectivity may represent parallel pathways to drive motor cortex output neurons in deep layers. One route originates from the thalamus and posterior cortical areas and arrives via the highly recurrent superficial layers of the motor cortex, whereas the other arrives directly from frontal cortical areas and the thalamus, bypassing the superficial layers (Hooks et al 2013, Kaneko 2013). The deep corticofugal neurons are themselves laminarly organized, with intratelencephalic-type neurons distributed from layers 5a to layer 6, pyramidal tract–type neurons restricted to layer 5b, and corticothalamic-type neurons restricted to layer 6 (Harris & Shepherd 2015).…”

“…Given the vertically descending transfer of information in the motor cortex (Weiler et al 2008) and the hierarchical flow of information from corticostriatal to corticospinal cells (Anderson et al 2010, Kiritani et al 2012), separate pathways may be used for different aspects of motor cortex function. Corticospinal cells may be the ultimate drivers of cortex-driven movement, but they can be accessed either directly by frontal cortical areas for general dexterous movements or indirectly by first going through learning-sculpted circuitry within layer 2/3 (Hooks et al 2013). …”