Know your brain: Locus coeruleus

Where is the locus coeruleus?

The locus coeruleus, which I'll refer to as the LC from here on out to avoid an inevitable misspelling, is a nucleus found in the pons. It is located near the floor of the fourth ventricle.

What is the locus coeruleus and what does it do?

The first descriptions of the LC date back to the late 1700s when French anatomist Félix Vicq d’Azyr detailed a blue-colored area of tissue in the pons. In the early 1800s, the term locus coeruleus, which means "blue spot" in Latin, was used to refer to that pigmented region. It wasn't until the second half of the twentieth century, however, that new techniques allowed scientists to learn that the blue coloring in the LC is caused by the production of a pigment formed by chemical reactions involving the neurotransmitter norepinephrine (also known as noradrenaline).

It is now known that the LC is the primary site of norepinephrine production in the brain. The nucleus sends norepinephrine throughout the cerebral cortex as well as to a variety of other structures including the amygdala, hippocampus, cerebellum, and spinal cord. In fact, the LC sends projections to virtually all brain regions except the basal ganglia, which seems to be lacking noradrenergic (i.e. noradrenaline/norepinephrine-related) input.

Because of the diversity of its projections and the diversity of the actions of norepinephrine as a neurotransmitter, the LC is involved in a long list of functions. It is perhaps most strongly linked, however, to arousal, vigilance, and attention. Neurons in the LC are less active during quiet wakefulness and their activity is even more diminished during sleep (indeed they are completely quiet during rapid eye movement, or REM, sleep), but they display increased activity in response to arousing stimuli. And optimal levels of norepinephrine in areas of the brain involved with attention, like the prefrontal cortex, have been found to be important to the facilitation of attention-related tasks.

Additionally, the LC and the norepinephrine it produces are thought to be integral to a number of higher cognitive functions ranging from motivation to working memory. It also seems to play a role in fine-tuning sensory signals to increase acuity across multiple sense modalities. It should be noted, however, that norepinephrine has wide-ranging actions throughout the brain and any attempt to briefly summarize its functions (or, by extension those of the LC) is an oversimplification.

Aging is associated with a significant loss of neurons in the LC, and a number of disorders---including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy---are linked to deficits in the number of LC neurons. In fact, in Alzheimer's disease the number of LC neurons lost exceeds the number of acetylcholine neurons lost in the nucleus basalis and in Parkinson's disease the number of LC neurons lost exceeds the number of dopamine neurons lost in the substantia nigra. This is notable because neuronal loss in the nucleus basalis and substantia nigra are considered hallmark signs of Alzheimer's disease and Parkinson's disease, respectively. Although the impact of LC loss in these diseases is not fully understood, it is thought to contribute significantly to the pathology of these conditions.


Counts SE, Mufson EJ. Locus Coeruleus. In: Mai JK and Paxinos G, eds. The Human Nervous System. 3rd ed. New York: Elsevier; 2012.

Sara SJ. The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci. 2009 Mar;10(3):211-23. doi: 10.1038/nrn2573.

2-Minute Neuroscience: Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are the most widely-used treatment for depression, and have been since their introduction to the market in the late 1980s. They were formulated based on the hypothesis that depression is caused by low levels of the neurotransmitter serotonin. In this video, I discuss how SSRIs work along with some questions that have been raised about the serotonin hypothesis since the introduction of SSRIs.

Know your brain: Inferior colliculus

Where is the inferior colliculus?


There are two inferior colliculi in the midbrain. They are symmetrically positioned, one on either side of the midline of the brainstem, and they form two bumps on the posterior surface of the brainstem just below the superior colliculi. The inferior colliculus is often subdivided into three regions: a central nucleus, dorsal cortex, and external cortex. The names of these last two regions are not completely consistent (e.g. some sources refer to the dorsal cortex as the pericentral nucleus and the external cortex as the lateral nucleus). The dorsal cortex and external cortex surround the central nucleus.

What is the inferior colliculus and what does it do?

The inferior colliculus is best known for its role in hearing. It is the largest nucleus of the auditory system in humans, and it is the point in the brainstem where all auditory pathways traveling through the brainstem converge. It is also the point from which auditory pathways branch out to carry auditory information on to other areas of the brain like the superior colliculus or thalamus.

The central nucleus of the inferior colliculus receives information from a number of auditory regions, including the cochlea itself as well as other areas like the superior olivary nuclei. The central nucleus also extends neuronal fibers to the medial geniculate nucleus of the thalamus, another important nucleus in the auditory pathway. From there, information travels to the cerebral cortex. Thus, the inferior colliculus acts as an important relay station for auditory information.

It's also thought, however, that the inferior colliculus plays important roles in integrating auditory information from various auditory nuclei, as well as in fine-tuning that information. The cells of the central nucleus of the inferior colliculus are organized tonotopically, meaning that different neurons respond preferentially to different frequencies of sound. Activation of neurons linked to a particular frequency, along with the inhibition of those that respond to different frequencies, may help to sharpen the perception of sound.

Additionally, neurons in the inferior colliculus are specialized to respond to cues (e.g. intensity, the difference in arrival time of a sound to both ears, etc.) that allow for the localization of sound, or the determination of where in space sound is coming from. This information is transmitted to the superior colliculus, which is involved with movement (e.g. of the head and eyes) in response to visual and auditory cues in the environment. There are also direct connections between the inferior colliculus and cortical areas involved in the control of gaze, perhaps to facilitate complex tasks of gaze control that involve aspects of memory, recognition, and other more sophisticated types of cognition.

These functions are all attributable to the central nucleus. The roles of the external and dorsal cortices are not as well understood. Although the external cortex receives input from auditory areas, it also receives information regarding bodily sensations, and is hypothesized to play a role in the representation of bodily position in respect to sounds in the environment. Damage to the dorsal cortex has been found to produce greater deficits in attention and vigilance than hearing, but its role is still in need of further clarification. 

Thus, more work needs to be done to completely understand the functions of the inferior colliculus, but at this point it is clear that the structure is an important component of the auditory pathway. It is involved in fine-tuning and integrating auditory sensations from a variety of other auditory regions, and sending that information on to the thalamus and cerebral cortex. It also is important to identifying the location of sound in space and orienting the body towards such sounds. Its other functions will likely become clearer with future research.

Oertel D, Doupe AJ. 2000. The Auditory Central Nervous System. In: Kandel ER, Schwartz JH, Jessell TM, eds. Principles of Neural Science, 5th ed. New York: McGraw-Hill.

Winer JA, Schreiner CH. 2005. The Central Auditory System: A Functional Analysis. In: Winer JA, Schreiner CH, eds. The Inferior Colliculus. New York: Springer Science + Business Media, Inc. 

Know your brain: Wernicke's area

Where is Wernicke's area?

approximate location of wernicke's area

Although the location of Wernicke's area is often presented in images and texts as definitive, there is some controversy about the exact location of the region. Typically, however, Wernicke's area is considered to reside in the cortex of the left cerebral hemisphere, surrounding a large groove called the lateral sulcus or Sylvian fissure, near the junction between the parietal and temporal lobes.

What is Wernicke's area and what does it do?

In the second half of the 19th century, neuroscientists were trying to come to grips with a new perspective on the brain that suggested that the two cerebral hemispheres were not completely equivalent in terms of function. The most convincing evidence to support this perspective at that point had been offered up by the famous physician Paul Broca, who had identified a number of cases where damage to the left hemisphere produced deficits in language---whereas damage to the right hemisphere was much less likely to do so. These observations coincided with Broca's identification of what would come to be known as Broca's area---a brain region typically found in the left hemisphere that is thought to be important to the production of speech (see this article for more about Broca's area).

This idea that one hemisphere could be more responsible for a behavior than the other---and in this case that the left hemisphere was dominant when it came to language---was mostly foreign to neuroscientists before Broca (although not completely unheard of as it had previously been proposed by the physician Marc Dax). Many were hesitant to accept it.

Left hemispheric dominance for language got some additional support, however, from the German physician Carl Wernicke in 1874. Wernicke reported that damage to a certain region in the left hemisphere often resulted in a speech deficit where patients were able to produce speech sounds that resembled fluent language, but actually were meaningless. These patients would string together incongruous syllables, neologisms, similar-sounding words substituted for one another, and so on, to produce speech that made little sense. Patients with this disorder, which would come to be known as Wernicke's aphasia, usually also suffer from a deficiency in their ability to understand language. You can see an example of Wernicke's aphasia in the video above.

Wernicke's aphasia contrasted with the syndrome Broca had observed after damage to Broca's area (that syndrome is known as Broca's aphasia). Patients with Broca's aphasia generally have difficulty producing the sounds necessary for speech. Often a patient with Broca's aphasia knows what he or she wants to say, but can't get the words out. Comprehension of language generally remains intact. You can see an example of Broca's aphasia in the video to the right. 

Because Wernicke's area seemed to play an important role in language comprehension and the production of language that was intelligible, Wernicke proposed a model for language that involved both his area and Broca's area. Wernicke's area, according to this model, generates plans for meaningful speech. Broca's area, on the other hand, is responsible for taking these plans and generating the movements (e.g. of the tongue,  mouth, etc.) required to turn them into vocalizations. To do so, Broca's area sends information about intended speech to the motor cortex, which then signals the muscles involved in speech production to create the vocalizations. Thus, according to this view, Wernicke's area makes sure that language makes sense, while Broca's area helps bring about the muscle movements necessary to actually produce the sounds.This model was later expanded upon by neurologist Norman Geschwind, and it eventually became known as the Wernicke-Geschwind model.

It is now thought, however, that this model is too simplistic. Language is a complex behavior made possible by a list of individual functions---ranging from the retrieval of particular phonemes to the adding of intonation and rhythm---that each likely involves widespread networks; it cannot simply be boiled down to a connection between two brain regions. Additionally, later studies have found that the functions of Broca's and Wernicke's areas are not as circumscribed as once thought. For example, Wernicke's area seems to play a role in speech production and Broca's area contributes to language comprehension. And damage to what is considered Wernicke's area does not always disrupt comprehension, which suggests Wernicke's area is just one component in a larger network involved in understanding language. 

Wernicke's area is thus not as anatomically well defined nor functionally well understood as many textbooks would lead you to think. It is thought to be important to language, but researchers are still trying to work out exactly what its role is. It's likely that it functions as part of a larger network, which---when fully understood---might allow us to appreciate the network as the important functional unit for language, rather than focusing so much on the individual brain regions that make up the network.


Binder, JR. The Wernicke area: Modern evidence and a reinterpretation. Neurology. 2015; 85(24): 2170-2175.

Breedlove SM, Watson NV. Biological Psychology. 7th ed. Sunderland, MA: Sinauer Associates, Inc.; 2013. 

Know your brain: Diencephalon

Where is the diencephalon?

general areas of the diencephalon colored red.

The diencephalon is a small part of the brain that is mostly hidden from view when you are looking at the outside of the brain. It is divided into four parts: the epithalamus, thalamus, subthalamus, and hypothalamus. The diencephalon can be found just above the brainstem between the cerebral hemispheres; it forms the walls of the third ventricle. The only part of the diencephalon that can be seen without taking a cross-section of the brain is the bottom-most portion of the hypothalamus.

What is the diencephalon and what does it do?

Despite being a relatively small part of the central nervous system in terms of mass, the diencephalon plays a number of critical roles in healthy brain and bodily function. Because it consists of a collection of structures, though, it would not make sense to try to define the functions of the diencephalon with one summary. Instead, I'll briefly touch on the roles of each of its sub-components, although it's important to realize that even these summaries will (by necessity) be simplified.


the epithalamus is circled in red.

The epithalamus consists primarily of the pineal gland and the habenulae. The pineal gland is an endocrine gland that secretes the hormone melatonin, which is thought to play an important role in the regulation of circadian rhythms. To learn more about the pineal gland, read this Know Your Brain article.

The habenulae (more often referred to with the singular: habenula) are two small areas near the pineal gland. The functions of the habenula are poorly understood, but it is thought to potentially be involved with reward processing and has been implicated in depression. Additionally, there is some evidence that the habenula also produces melatonin, and that it might be involved with sleep regulation. To learn more about the habenula, read this Know Your Brain article.


approximate area of the subthalamus circled in red.

A portion of the subthalamus is made up of tissue from the midbrain extending into the diencephalon. Thus, parts of midbrain regions like the substantia nigra and red nucleus are found in the diencephalon. The subthalamus is also home to the subthalamic nucleus and the zona incerta. The subthalamic nucleus is densely interconnected with the basal ganglia, and plays a role in modulating movement. The zona incerta has many connections throughout the cortex and spinal cord, but its function is still not determined. Several collections of important fibers (e.g. somatosensory fibers) also pass through the subthalamus.


the thalamus colored in red. There are two of these structures in an intact brain. they are symmetrical and positioned side-by-side one another.

The thalami (more frequently referred to with the singular: thalamus) consist of two oval collections of nuclei that make up most of the mass of the diencephalon. The thalamus is often described as a relay station because almost all sensory information (with the exception of smell) that proceeds to the cortex first stops in the thalamus before being sent on to its destination. The structure is subdivided into a number of nuclei that possess functional specializations for dealing with particular types of information. Sensory information thus travels to the thalamus and is routed to a nucleus tailored to dealing with that type of sensory data. Then, the information is sent from that nucleus to the appropriate area in the cortex where it is further processed.

The thalamus doesn't deal just with sensory information, however. It also receives a great deal of information from the cerebral cortex, and it is involved with processing that information and sending it back to other areas of the brain. Due to its involvement in these complex networks, the thalamus plays a role in a number of important functions ranging from sleep to consciousness. To learn more about the thalamus, read this Know Your Brain article


hypothalamus colored in red.

The hypothalamus is a small (about the size of an almond) region located directly above the brainstem. It also is made up of a collection of nuclei that are involved in a variety of functions. The hypothalamus is often linked, however, to two main roles: maintaining homeostasis and regulating hormone release.

Homeostasis is the maintenance of equilibrium in a system like the human body. Optimal biological function is facilitated by keeping things like body temperature, blood pressure, and caloric intake/expenditure at a fairly constant level. The hypothalamus receives a steady stream of information about these types of factors. When it recognizes an unanticipated imbalance, it enacts a mechanism to rectify that disparity.

The hypothalamus acts to maintain homeostasis---and influences behavior in general---by regulating hormone secretion. This is primarily done through the control of hormone release from the pituitary gland. Through this mechanism, the hypothalamus has widespread effects on the body and behavior. It is often said that the hypothalamus is responsible for the four Fs: fighting, fleeing, feeding, and fornication. Clearly, due to the frequency and significance of these behaviors, the hypothalamus is extremely important in everyday life. To learn more about the hypothalamus, read this Know Your Brain article.


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