Video: Layers and cells of the cerebral cortex

The cerebral cortex is just a few millimeters thick, but it lets us perform some incredibly complex tasks. How is this possible?

Well, one of its secrets is that cortical neurons are not lumped together like a bowl of overcooked spaghetti. Instead, the cerebral cortex resembles a layered cake. Crunchy cookie crumbs, soft sponge, and fresh frosting all have different flavor and consistency, but all layers work together to deliver an incredible taste experience.

Let's discover how structure facilitates brain functions by discussing the layers of the cerebral cortex.

The cerebral cortex is arranged in layers of neurons that have similar functions and connections. The neocortex usually has six layers, but other regions like the allocortex may comprise only three or four layers. Scientists discovered that the cortex is arranged in layers after developing staining techniques that can reveal the structural characteristics of cells in a tissue.

The Nissl technique highlights the rough endoplasmic reticulum inside the neurons. Since this structure is primarily present in the neuron body, this stain reveals the density, size, and shape of neurons.

This is a drawing of what a Nissl stain looks like. It's easy to see that only a few neuron bodies are located near the surface of the cortex compared to deeper regions. Neuron bodies can have one of a few different shapes, and it's important to note that there are smaller and larger neurons.

The Nissl technique is however unable to show neuronal connections. These can be studied using a different stain called Weigert technique, which emphasizes the myelin sheets wrapped around the axons. The Weigert stain shows that axons are oriented either vertically or horizontally, depending on their depth. This information suggests that regions of the cortex at different depths have different functions.

Horizontal connections represent neurons mainly dedicated to processing information within the layer, whereas vertical connections identify neurons that carry information between layers or outside the cortex.

A third staining technique developed by Camillo Golgi shows the body and the dendrites of a small random subset of neurons. This stain helps visualize neurons in their entirety, including their dendritic processes that are otherwise difficult to study. Using these techniques, neuroscientists discovered that the cortex is organized in layers composed of different types of neurons.

Let's dive deeper into the types of cortical neurons.

Most cortical neurons have one of three morphological shapes: pyramidal, fusiform, or stellate. These neurons are generally located in different layers of the cortex. When talking about the location of a neuron, we mean the layer where its body is located. On the other hand, its axon and dendrites may span multiple layers.

Pyramidal cells are commonly found in layers III and V and constitute around 75 percent of the cellular component of the cerebral cortex. Pyramidal cells typically have one apical dendrite that reaches the surface of the cortex, multiple basal dendrites in the vicinity of the cell body, and one long axon.

Pyramidal cells contribute to different types of white matter tracts. They form commissural connections when their axon reaches cortical areas in the other hemisphere; association connections when they reach ipsilateral association areas; and projection connections when they project to different structures of the central nervous system like the spinal cord and thalamus.

Fusiform cells are oriented vertically with dendrites that project towards the cortical surface. They also have a long axon. Like pyramidal cells, they can also form commissural, association, or projection connections.

Pyramidal and fusiform cells are also called projection neurons because their axons can reach outside the local cortical areas.

Stellate cells are small interneurons that resemble a star with short dendritic processes that extend in all planes. They are primarily found in layer IV of the cortex and project locally within the layer. There are two types of stellate cells.

Spiny stellate cells have spines on their dendrites. They form excitatory synapses using glutamate and often assists with intracortical processing in sensory areas. Aspiny stellate cells have no spines on their dendrites and release GABA to inhibit the neurons they synapse with.

Neurons of other shapes can be found in the cerebral cortex, but they are less common. These include the Cajal-Retzius cells, also known as horizontal cells, which are exclusively found in the superficial layer and have dendrites oriented horizontally; and inhibitory interneurons like basket cells and the cells of Martinotti.

Now that we've seen the different types of neurons, let's take a look at their location in the different layers of the cortex.

From superficial to deep, the six layers of the neocortex are called layer I, molecular, or the plexiform layer; layer II, the external granular layer; layer III, the external pyramidal layer; layer IV, the internal granular layer; layer V, the internal pyramidal layer; and layer VI, the multiform or fusiform layer.

These names reflect their dominant cell type. For instance, the granular layers have small round cells, whereas the pyramidal layers contain many pyramidal cells. The names also reflect the depth. The external layers are more superficial than the internal layers.

Let's talk about the main features of the different levels.

The molecular layer contains predominantly axons and dendrites of neurons located in other layers, and a few horizontal cells of Cajal-Retzius. The external granular layer contains a varying density of stellate cells and small pyramidal cells, while the external pyramidal layer consists predominantly of pyramidal cells.

Layers 1 to 3 are often referred to as the supragranular part of the cerebral cortex. These neurons predominantly connect with other cortical regions through association and commissural projections.

The internal granular layer consists mostly of stellate cells, which synapse locally. It also contains pyramidal cells that synapse deeper within the cortex or join white matter fiber tracts.

Layer IV receives sensory information through the thalamus and sends signals to the rest of the column. It is especially developed within sensory areas like the visual and the somatosensory cortex. The internal pyramidal layer consists predominantly of medium and large pyramidal cells which often projects to the brainstem and the spinal cord. This layer is most prominent within the motor cortex.

Layer V of the motor cortex contains a specific form of pyramidal cells called the cells of Betz, which are especially vulnerable to motor neuron disease.

Finally, the multiform layer is the closest to the white matter and primarily contains fusiform cells and a small proportion of pyramidal cells and interneurons. Many neurons in layer VI form reciprocal connections with the thalamus.

The two deepest layers of the cortex are also called the infragranular part of the cortex. Most of the neurons in these layers send information outside of the cortex, joining white matter fiber tracts that project to the thalamus, the spinal cord, and other areas of the central nervous system.

This is how the layered structure of the cerebral cortex helps neurons receive, integrate, and send information efficiently to make us perform a number of truly remarkable tasks, including eating cake.

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