PDF version: Primer on the Biology of the Cerebral Cortex
On the axial dimension, the cerebral cortex is partitioned into six layers of cells. Layer 1 of the cerebral cortex is the most superficial and layer 6 is the deepest relative to the surface of the brain. Layers 2 and 3 are often categorized together as layer 2/3. Laterally, the cerebral cortex is tiled by distinct regions called cortical columns which act as repeating units of similar function.
Layer 1 and layer 2/3 are called the supragranular layers and mostly perform intracortical computations. Layer 4 is called the granular layer and functions primarily to receive thalamic input. Layers 5 and 6 are called the infragranular layers and mainly send outputs to other parts of the brain.
Though the majority of cortical cells are excitatory pyramidal neurons, there are also many inhibitory interneurons which are crucial to cortical function. There are many morphologically distinct classes of inhibitory interneurons. Pyramidal cells also exhibit structural diversity, though their morphological differences are less often discussed in an explicit fashion.
Canonical cortical microcircuit
The canonical cortical microcircuit is a model for some of the most frequently occurring patterns of cortical connectivity and function. Some neuroscientists hypothesize that most cortical circuits are variations of a canonical microcircuit. Though different authors have suggested somewhat different versions of the canonical cortical microcircuit model, there are some common patterns as follows.
According to the canonical cortical microcircuit model, strong thalamic inputs first arrive at layer 4 and stimulate both the layer’s inhibitory interneurons and its excitatory pyramidal neurons. Next, these layer 4 neurons transmit information to layer 2/3 pyramidal cells which in turn send excitatory projections to layers 5 and 6 (as well as to layer 1). Layers 5 and 6 send both excitatory and inhibitory signals to other parts of the brain (e.g. back to the thalamus, to the brainstem, etc.) Layers 5 and 6 also send both excitatory and inhibitory feedback to layer 4.
Cortical hierarchy and extrinsic connections
Links among neurons within a cortical column are referred to as intrinsic connections while links between neurons in different cortical columns are called extrinsic connections. Though the majority of cortical connections are intrinsic, the extrinsic connections often stimulate (via activation and inhibition) their targets more strongly.
There are three types of extrinsic connections; feedforward, feedback, and lateral connections. Feedforward connections are from supragranular pyramidal cells to layer 4, feedback connections are from infragranular pyramidal cells to any layer except layer 4 (usually the supragranular layers), and lateral connections are between cells in the same layer. By using this laminar system, a cortical hierarchy emerges with lower cortical areas such as V1 sending information to higher cortical areas such as the dorsal and ventral visual streams via feedforward connections.
Feedback connections are usually inhibitory and can be either modulatory or driving. Though only excitatory lateral connections are shown in the figure above, lateral connections vary in whether they are excitatory, inhibitory, modulatory, or driving. Modulatory connections produce weak metabotropic and ionotropic responses while driving connections produce strong ionotropic responses.
Extrinsic connections are mostly from excitatory glutamatergic neurons, yet feedback connections are usually inhibitory. As such, it is thought that feedback connections typically involve excitatory neurons stimulating layer 1 cells which subsequently send inhibitory projections to layer 2/3 pyramidal cells.
Feedforward connections are excitatory and driving. Feedforward connections might operate as either corticocortical links or as transthalamic links. Transthalamic refers to when a cortical projection goes to the thalamus and then the postsynaptic thalamic neuron sends an axon back to some other part of the cortex.
Reference: Bastos, A. M., Usrey, W. M., Adams, R. A., Mangun, G. R., Fries, P., & Friston, K. J. (2012). Canonical Microcircuits for Predictive Coding. Neuron, 76(4), 695–711. https://doi.org/https://doi.org/10.1016/j.neuron.2012.10.038