Know your brain: Periaqueductal gray

Where is the periaqueductal gray?

periaqueductal gray

The periaqueductal gray, or PAG, is an area of gray matter found in the midbrain. The PAG surrounds the cerebral aqueduct (hence the name periaqueductal) and occupies a column of brainstem that stretches about 14 mm long. There are no obvious visible anatomical divisions within the PAG, but researchers have divided the PAG into four columns based on differences in connectivity and function: the dorsomedial, dorsolateral, lateral, and ventrolateral columns. For the sake of simplicity, however, below I will discuss the PAG as a whole instead of partitioning it using this columnar organization.

What is the periaqueductal gray and what does it do?

Although the functions of the PAG are complex and not fully understood, since the 1970s it has best been known for its role in the inhibition of pain. Indeed, some have argued that its identification as an "analgesia center" has hindered a more complete understanding of the functions of the PAG. An increasingly intricate appreciation of PAG function, however, has been emerging over the past few decades

When the PAG was first found to have an association with pain, it was observed as playing a role in pain transmission---or the sending of pain signals to the cortex---and not the mitigation of those signals. Eventually, the PAG would come to be much better recognized as an area important to pain inhibition. In the late 1960s, the first indication of the role of the PAG in pain suppression emerged from a study that found that stimulation of the PAG in rats allowed researchers to perform surgery on the rats without the use of anesthetics (and without the animals exhibiting signs of severe pain). Further studies found that PAG activation was associated with the inhibition of spinal cord neurons involved in pain signaling. By the mid-1970s, stimulation of the PAG was already being used as an experimental approach to treating chronic pain in human patients. The fact that some of these experiments reported success in the treatment of chronic pain supported the role of the PAG in analgesia. The patients involved in these experiments also often complained of a wide range of side effects linked to PAG stimulation, however, suggesting that many more functions than analgesia were connected to the PAG.

Still, due to the seminal findings involving the PAG and pain reduction, the PAG became best known for its role in analgesia. Although this has been a recognized function of the PAG for several decades, the full complexities of the mechanism underlying PAG-facilitated analgesia are still not completely understood. The main pathway seems to involve neurons that project from the PAG to nuclei of the medulla---primarily the raphe nuclei, which are clusters of serotonin-producing neurons. Activated raphe neurons project down to the spinal cord where they inhibit neurons in the dorsal horn of the spinal cord that are responsible for transmitting pain signals.  This pathway seems to be involved in a variety of pain inhibition responses, including analgesia experienced during acutely stressful events and the pain relief we obtain from taking opioid painkillers.

Interest in the PAG's role in pain inhibition has caused the other known functions of the PAG to often be overlooked; it's clear, however, that the PAG is involved in much more than just analgesia. For example, the PAG appears to play a part in the regulation of heart rate and blood pressure, and it is thought that the PAG may help to adjust cardiovascular activity in the context of particular emotional experiences. The PAG also seems to contribute to a number of other autonomic processes, and it is important to the control and contraction of the bladder in humans and other animals. The PAG plays a role in the production of vocalizations; stimulation of the PAG can elicit vocalizations in animals and lesions of the PAG can disrupt them in humans and other animals. In an attempt to understand the contributions of the PAG to vocalizations, some have hypothesized that the PAG is important to coordinating respiratory and laryngeal motor patterns that facilitate the production of vocalizations. The PAG also seems to be involved with emotional responses. It appears to be especially likely to be infuential in the production of fearful and defensive reactions, as stimulation of the PAG can elicit these types of reactions in a variety of animals; human participants also displayed activation of the PAG when a threat came closer to them. 

There are still many other functions associated with the PAG that have not been mentioned here. Thus, despite being a relatively small area of the brain, the PAG is densely interconnected with various other brain regions, and seems to be involved in a diverse range of functions. It is therefore understandable why some researchers believe calling it an "analgesia center" is representative of a limited perspective on the PAG.


Behbehani, M. (1995). Functional characteristics of the midbrain periaqueductal gray Progress in Neurobiology, 46 (6), 575-605 DOI: 10.1016/0301-0082(95)00009-K

Carrive P, Morgan MM. Periaqueductal Gray. JK Mai and G Paxinos (Eds.). 2012; Elsevier, New York.

2-Minute Neuroscience: Amygdala

In this video, I discuss the amygdala. The amygdala is a collection of nuclei found in the temporal lobe; it is best known for its role in fear and threat detection, but its full range of functions is much more diverse. I discuss some of the major nuclei of the amygdala, a common scheme for the anatomical organization of the amygdalar nuclei, and some of the functions that have been associated with the amygdala ranging from threat detection to the processing of positive stimuli.

Know your brain: Superior colliculus

Where is the superior colliculus?

posterior view of the brainstem showing the superior colliculi.

posterior view of the brainstem showing the superior colliculi.

There are two superior colliculi in the midbrain. They are symmetrically positioned, one on either side of the midline of the brainstem; they form two bumps on the posterior external surface of the brainstem. The superior colliculi are just below the thalamus and above the two inferior colliculi. The superior colliculus is often referred to as the tectum or optic tectum in non-human vertebrates.

What is the superior colliculus and what does it do?

Although the complete scope of functions that can be attributed to the superior colliculi has not been fully delineated, the superior colliculi are understood to be important to directing behavioral responses toward stimuli in the environment. In other words, the superior colliculus seems to be able to receive information from the environment and then use that information to initiate a behavioral response appropriate to the current environmental context. For example, if you were sitting in the stands at a baseball game and someone hit a home run, you would follow the ball with your head and eyes. This behavioral response to an environmental stimulus would involve the superior colliculi. In fact, eye and head movements like this are the most-studied function of the superior colliculus, but the structure is thought to be involved in a variety of other responsive movements as well.

The superior colliculus is made up of several layers of cells, which anatomists have divided into what are called superficial and deep layers. The superficial layers seem to primarily receive visual information from the retina and the visual cortex, while the deep layers receive information from the auditory, visual, and somatosensory systems. The deep layers also appear to be where the motor functions of the superior colliculus originate, as stimulation of neurons in these layers can produce a variety of movements.

The different layers of the superior colliculi contain what are known as topographic maps for the sense modalities they process information from. The term topographic map in neuroscience is used to refer to an organization where sensory input from a particular region of the body is sent to a specific area of the central nervous system. For example, information from a particular part of the visual field is sent to a corresponding region of the superficial layers of the superior colliculus. Because all of the layers of the superior colliculus have a similar topographic arrangement, it allows for the rapid integration and enhancement of signals that arrive via multiple sense modalities (e.g. vision and hearing). Additionally, because the motor areas of the superior colliculus have the same topographic arrangement as the sensory areas, it allows for the rapid initiation of motor responses to incoming sensory information.

In many other vertebrates (e.g. fish, birds), the superior colliculus is one of the largest brain regions. In humans this is not the case, as it is dwarfed by a number of other structures. Despite its relatively small size, however, the superior colliculus plays a very important role in integrating sensory information and quickly triggering behavioral reactions to it.


King AJ. The Superior Colliculus. Current Biology. 2004;14(9):R335-8.

2-Minute Neuroscience: Striatum

In this video, I discuss the striatum. The term striatum is used to refer collectively to the caudate nucleus, putamen, and nucleus accumbens. The striatum is one of the primary structures of the basal ganglia, a group of structures best known for their role in facilitating movement. The striatum is also thought to be important to the processing of rewarding experiences and seems to be involved in the development of addiction.


Read more: Know your brain - Striatum

                     Know your brain - Nucleus accumbens

                     Know your brain - Basal ganglia

                     Know your brain - Reward system

Watch these 2-Minute Neuroscience videos to learn more about the basal ganglia and reward system:

                     2-Minute Neuroscience - Basal Ganglia

                     2-Minute Neuroscience - Reward System

Know your brain: Primary visual cortex

Where is the primary visual cortex?

primary visual cortex (in red).

primary visual cortex (in red).

The primary visual cortex is found in the occipital lobe in both cerebral hemispheres. It surrounds and extends into a deep sulcus called the calcarine sulcus. The primary visual cortex makes up a small portion of the visible surface of the cortex in the occipital lobe, but because it stretches into the calcarine sulcus, it makes up a significant portion of cortical surface overall. The primary visual cortex is sometimes also called the striate cortex due to the presence of a large band of myelinated axons that runs along the eges of the calcarine sulcus. These axons, referred to as the line of Gennari in reference to the first researcher who made note of their presence in the late 1700s, make the primary visual cortex appear striped (striate comes from Latin and implies a striped appearance).

What is the primary visual cortex and what does it do?

The primary visual cortex, often called V1, is a structure that is essential to the conscious processing of visual stimuli. Its importance to visual perception is underscored by cases where patients have experienced damage to V1; these patients generally experience disruptions in visual perception that can range from losing specific aspects of vision (e.g. depth perception) to complete loss of conscious awareness of visual stimuli.

When visual information leaves the retina, it is sent via the optic nerve (which soon becomes the optic tract) to a nucleus of the thalamus called the lateral geniculate nucleus. From there, it is carried in a tract often called the optic radiation, which curves around the wall of the lateral ventricle in each cerebral hemisphere and reaches back to the occipital lobe. The axons included in the optic radiation terminate in the primary visual cortex in what is called a retinotopic manner, meaning that axons carrying information from a specific part of the visual field terminate in a location in V1 that corresponds to that location in the visual field. For example, axons carrying information about the inferior portion of the visual field terminate in areas of V1 that lie above the calcarine sulcus, while those that carry information about the superior portion of the visual field project to areas below the calcarine sulcus.

These projections to the primary visual cortex from the thalamus travel along at least three distinct pathways. One pathway arises from large neurons in the retina called magnocellular, or M, cells; another pathway projects from smaller neurons called parvocellular, or P, cells; and a third pathway travels to V1 from small neurons called koniocellular, or K, cells. These different types of neurons preferentially respond to different types of visual stimuli, thus it seems these pathways are each somewhat specialized for specific categories of stimuli. M cells, for example, seem to be specialized to detect movement (e.g. location, speed, and direction of movement of a moving object). P cells appear to be important for spatial resolution (e.g. shape, size, and color of an object) and are also involved in color vision. The functions of K cells are still not fully understood, but they are thought to be involved with some aspects of color vision.

Neurons in the primary visual cortex are arranged into columns of neurons that have similar functional properties. For example, neurons in one column might respond primarily to stimuli that have a certain orientation (e.g. upright vs. horizontal) and are perceived by the contralateral eye. Neurons in another column might also respond primarily to upright orientation, but only when the information is coming from the ipsilateral eye. These columns of neurons are themselves collected into assemblies sometimes called modules; each module contains an array of neuronal columns necessary to analyze one small area of the visual field. Thus, to complete the visual scene, the primary visual cortex has many of these modules under the cortical surface.

The areas of the occipital lobe surrounding the primary visual cortex are also primarily involved with vision. Sometimes collectively referred to as extrastriate cortex, the function of these areas in relation to the primary visual cortex is not fully understood, but they are thought to play important roles in visual processing. One popular conceptualization of how the primary visual cortex is functionally linked to the extrastriate areas is that there are two main pathways by which information travels from V1 to the surrounding visual areas. One pathway, referred to as the ventral stream for its path along the ventral portion of the brain, passes from V1 to the extrastriate areas and on to the inferior part of the temporal lobe; it is thought that the ventral stream primarily carries information involved with object form and recognition. A second pathway, the dorsal stream, travels from V1 to the extrastriate areas and then to the posterior parietal lobe; it is thought to be involved with perceiving motion and spatial relationships between objects in the visual field. Sometimes the ventral stream is called the "what" pathway due to its role in identifying objects, while the dorsal stream is called the "where" pathway because of its involvement in analyzing the movement of those objects.

Although a great deal is known about the primary visual cortex and the visual system in general, there is still much to be understood about how activity in different areas of V1---and activity in the extrastriate areas---comes together to coherently reproduce all of the intricate characteristics of a visual scene. The visual areas of the brain are a great example of just how complex the brain is, for they have probably been studied more than any other brain region, yet there are still many unanswered questions about exactly how they work to create the rich experience we call visual perception.

Purves D, Augustine GJ, Fitzpatrick D, Hall WC, Lamantia AS, McNamara JO, White LE. Neuroscience. 4th ed. Sunderland, MA. Sinauer Associates; 2008.

Vanderah TW, Gould DJ. Nolte's The Human Brain. 7th ed. Philadelphia, PA: Elsevier; 2016.