The motor cortex (M1) is classically considered an agranular area, lacking a distinct layer 4 (L4). Here, we tested the idea that M1, despite lacking a cytoarchitecturally visible L4, nevertheless possesses its equivalent in the form of excitatory neurons with input–output circuits like those of the L4 neurons in sensory areas. Consistent with this idea, we found that neurons located in a thin laminar zone at the L3/5A border in the forelimb area of mouse M1 have multiple L4-like synaptic connections: excitatory input from thalamus, largely unidirectional excitatory outputs to L2/3 pyramidal neurons, and relatively weak long-range corticocortical inputs and outputs. M1-L4 neurons were electrophysiologically diverse but morphologically uniform, with pyramidal-type dendritic arbors and locally ramifying axons, including branches extending into L2/3. Our findings therefore identify pyramidal neurons in M1 with the expected prototypical circuit properties of excitatory L4 neurons, and question the traditional assumption that motor cortex lacks this layer.
In 1909, a German scientist called Korbinian Brodmann published the first map of the outer layer of the human brain. After staining neurons with a dye and studying the structures of the cells and how they were organized, he realized that he could divide the cortex into 43 numbered regions.
Most Brodmann areas can be divided into a number of horizontal layers, with layer 1 being closest to the surface of the brain. Neurons in the different layers form distinct sets of connections, and the relative thickness of the layers has implications for the function carried out by that area. It is thought, for example, that the motor cortex does not have a layer 4, which suggests that the neural circuitry that controls movement differs from that in charge of vision, hearing, and other functions.
Yamawaki et al. now challenge this view by providing multiple lines of evidence for the existence of layer 4 in the motor cortex in mice. Neurons at the border between layer 3 and layer 5A in the motor cortex possess many of the same properties as the neurons in layer 4 in sensory cortex. In particular, they receive inputs from a brain region called the thalamus, and send outputs to neurons in layers 2 and 3.
Yamawaki et al. go on to characterize some of the properties of the neurons in the putative layer 4 of the motor cortex, finding that they do not look like the specialized ‘stellate’ cells that are found in some other areas of the cortex. Instead, they resemble the ‘pyramidal’ type of neuron that is found in all layers and areas of the cortex.
The discovery that the motor cortex is more similar in its circuit connections to other area of the cortex than previously thought has important implications for our understanding of this region of the brain.