Top-down laminar organization of the excitatory network in motor cortex

Abstract

Cortical layering is a hallmark of the mammalian neocortex and a major determinant of local synaptic circuit organization in sensory systems. In motor cortex, the laminar organization of cortical circuits has not been resolved, yet their input-output operations are crucial for motor control. Here, we developed a general approach for estimating layer-specific connectivity in cortical circuits, and applied it to mouse motor cortex. From these data we computed a laminar presynaptic→postsynaptic connectivity matrix, W post,pre , revealing a complement of stereotypic pathways dominated by layer 2 outflow to deeper layers. Network modeling predicted, and experiments with disinhibited slices confirmed, that stimuli targeting upper but not lower cortical layers effectively evoked network-wide events. Thus, in motor cortex, descending excitation from a preamplifier-like network of upper-layer neurons drives output neurons in lower layers. Our analysis provides a quantitative wiring diagram framework for further investigation of the excitatory networks mediating cortical mechanisms of motor control.Motor cortex is centrally involved in mammalian motor behavior and the cortical control of movement. Motor cortex has long been studied in terms of its motor output, and much is known about how corticospinal neuron activity correlates with movement. The large-scale networks linking motor cortex with other cortical and subcortical motor systems are also well characterized. Multiple long-range excitatory input pathways converge on primary somatic motor cortex (M1). These include corticocortical projections (carrying ipsi-and contralateral sensorimotor information), thalamocortical projections (carrying cerebellar and basal ganglionic information via the thalamic ventrolateral nucleus, as well as sensory and other information via multiple additional thalamocortical pathways), and neuromodulatory projections from brainstem and other areas (reviewed in 1 ). Major outputs from M1 include projections to spinal/bulbar motor centers, striatum, thalamus, subthalamus, red nucleus, and pons. All excitatory neurons in M1 are pyramidal neurons projecting to one or several of these long-distance targets. Corticofugal outflow to the pyramidal/extrapyramidal motor systems and thalamus originates primarily from cells in middle and deeper layers, while corticocortical connections arise from cells in both upper and deeper layers.

Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain

“…The observed morphological changes were limited to the basal dendrites; this suggests a pathway-specific phenomenon. Basal dendrites of layer 2/3 neurons receive inputs from other layer 2/3 pyramidal neurons and from deeper cortical layers (27)(28)(29). Thus, morphological changes of basal dendrites may suggest reorganization of intracortical circuits more than changes related to the reorganization of extracortical inputs, which may depend on the surgical deafferentation.…”

Specialized Cortical Subnetworks Differentially Connect Frontal Cortex to Parahippocampal Areas

“…The excitatory connection from upper L5 to upper L2/3 has been established in primary motor, and primary and secondary somatosensory areas (Shepherd and Svoboda, 2005;Bureau et al, 2006;Weiler et al, 2008;Lefort et al, 2009;Hooks et al, 2011). In frontal cortex, backward connection from L5 to L2/3 PRCprojecting cells shows lower connection probability and somewhat smaller and more variable EPSCs than forward connections ( Table 2).…”

Hierarchical excitatory synaptic connectivity in mouse olfactory cortex

“…Although our experiments were conducted under disinhibited conditions to allow us to isolate the excitatory network, normal cortical activity of course is shaped by inhibition (30). However, block of inhibition has been used to good advantage in other cortical areas to focus on relevant network dynamics, revealing spiral waves in neocortex (37) and laminar features of excitatory circuits in motor cortex (38). The variance patterns of burst activity in our experiments, when combined with network modeling, provided insight into the architecture of the intrinsic excitatory circuitry as well as the functional excitatory connectome on the synaptic scale.…”