2-Minute Neuroscience: Nucleus Accumbens

In this video, I discuss the nucleus accumbens. The nucleus accumbens is located in the basal forebrain, and is the major component of the ventral striatum. Although it is best known as a key structure in the reward system, the role of the nucleus accumbens in reward is still not fully understood. This is due in part to the fact that the nucleus accumbens also seems to be activated in response to aversive stimuli, and thus some have suggested that it is involved in responses to all motivationally-relevant stimuli---whether positive or negative.

Know your brain: Suprachiasmatic nucleus

Where is the suprachiasmatic nucleus?

the suprachiasmatic nucleus is represented by a small green area within the hypothalamus (indicated by red arrow).

the suprachiasmatic nucleus is represented by a small green area within the hypothalamus (indicated by red arrow).

The suprachiasmatic nuclei are two small, paired nuclei that are found in the hypothalamus. Each suprachiasmatic nucleus only contains approximately 10,000 neurons. The nuclei rest on each side of the third ventricle, just above the optic chiasm. The location provides the rationale for the naming of the structure, as supra means above and chiasmatic refers to its proximity to the optic chiasm. 

What is the suprachiasmatic nucleus and what does it do?

Circadian rhythms are biological patterns that closely follow a 24-hour cycle. The term circadian comes from the Latin for around (circa) and day (diem), and circadian rhythms govern a large number of biological processes including sleeping, eating, drinking, and hormone release. In the 1960s, researchers noticed that damage to the anterior hypothalamus of the rat caused a disruption in the animal's circadian rhythms. Several years later, the specific nucleus in the hypothalamus whose integrity was necessary for maintaining circadian rhythms was identified as the suprachiasmatic nucleus.

We now know that the suprachiasmatic nucleus houses a type of biological clock that is able to keep our circadian rhythms on close to a 24-hour cycle, even without the help of external cues like daylight. Thus, if you were to lock someone in a room with no external light and no other way of telling the time, her body would still maintain a circadian rhythm of around 24 hours. The mechanism that regulates this biological clock was first elucidated in Drosophila, more commonly known as the fruit fly.

In Drosophila, the timekeeping of the circadian clock appears to be controlled by a cycle of gene expression that has an ingenious negative feedback mechanism built into it. Cells in the suprachiasmatic nuclei of Drosophila produce two proteins called Clock and Cycle. Clock and Cycle bind together and act to promote the expression of two genes called period (per) and cryptochrome (cry). The protein products of these two genes, Per and Cry, then bind together and proceed to inhibit the actions of Clock and Cycle, an action which in turn suppresses the production of Per and Cry. Gradually, however, the Per and Cry proteins begin to break down. When Per and Cry degrade fully, Clock and Cycle are free to act again; they go back to promoting the expression of per and cry, starting the cycle anew. The process consistently takes around 24 hours to complete before it repeats. Thus, it is thought that this cycle of gene expression is what acts as the molecular clock in Drosophila suprachiasmatic nucleus cells.

This understanding of the timekeeping mechanism in Drosophila laid the foundation for elucidating the process in mammals, where it is thought to be similar but more complex. The mammalian version of Cycle is called BMAL1 (which stands for brain and muscle ARNT-like 1). When CLOCK and BMAL1 bind together, they enhance the transcription of a family of genes that includes multiple period (Per1, Per2, and Per3) and cryptochrome (Cry1 and Cry2) genes. The resultant PER and CRY proteins form complexes along with other proteins to inhibit the activity of CLOCK and BMAL1 until the PER and CRY proteins degrade (as above). 

We know that this process of gene expression and inhibition acts to keep a 24-hour clock within the neurons of the suprachiasmatic nucleus, but less is known about how the timekeeping within these neurons leads to the regulation of rhythmic activity throughout the body. It is believed, however, that the molecular clocks found within the neurons of the suprachiasmatic nuclei regulate neural activity within the nuclei, which in turn coordinates the activity of multiple signaling pathways as well the stimulation of projections to neuroendocrine neurons in the hypothalamus involved with hormone release.

Additionally, the suprachiasmatic nucleus helps to maintain circadian rhythms by coordinating the timing of billions of other circadian clocks found in cells throughout the rest of the brain and body. Not long after the discovery of the suprachiasmatic nucleus, it was also learned that similar types of molecular clocks exist in most other peripheral tissues and in many areas of the brain. These clocks, sometimes called slave oscillators (while the suprachiasmatic nucleus is considered the master oscillator) appear to depend on signals generated by the suprachiasmatic nucleus to synchronize their time-keeping with that of the suprachiasmatic nucleus. These signals can be associated with rhythms that the suprachiasmatic nucleus helps to establish, like feeding patterns, rest and activity behaviors, etc., or by direct neuronal or hormonal output from the suprachiasmatic nucleus.

Although the suprachiasmatic nucleus is capable of maintaining circadian rhythms independently of any environmental signals (e.g. daylight), it does rely on cues from the environment to make adjustments to the circadian clock. For example, when you fly across multiple time zones, your body's circadian clock becomes significantly out of sync with the timing of the day (e.g. your body might be preparing for sleep when it is still light out). To make adjustments to the circadian clock in such instances, the suprachiasmatic nucleus relies on information it receives from the retina about light in the environment. Such information travels from the retina to the suprachiasmatic nucleus along a path called the retinohypothalamic tract. Additional inputs to the suprachiasmatic nucleus provide more information about light in the environment and other non-photic information about time of day to help to adjust the circadian clock.

Due to the importance of our circadian rhythms to normal functioning, the integrity of the suprachiasmatic nucleus is essential to health. Disrupted function of the suprachiasmatic nucleus is being explored as a potential influence in a variety of psychiatric disorders as well as a factor in age-related decline in healthy sleep. Thus, although we have much more to learn about the suprachiasmatic nucleus, it is clear that it plays a very critical role in healthy brain and bodily function.

Colwell, C. (2011). Linking neural activity and molecular oscillations in the SCN Nature Reviews Neuroscience, 12 (10), 553-569 DOI: 10.1038/nrn3086

Dibner, C., Schibler, U., Albrecht, U. (2010). The mammalian circadian timing system: organization and coordination of central and peripheral clocks Annual review of physiology, 72 (1), 517-549.

2-Minute Neuroscience: Ventral Tegmental Area

In this video, I discuss the ventral tegmental area, or VTA. The VTA is one of the two largest dopaminergic regions of the brain (the other being the substantia nigra). Dopamine neurons leave the VTA in several different pathways and project throughout the brain. The mesocortical pathway projects from the VTA to widespread areas of the cerebral cortex and has diverse functions including motivation, emotion, and executive functions. The mesolimbic pathway projects from the VTA to several limbic structures; the largest projection is to the nucleus accumbens. The mesolimbic pathway also has diverse functions but is best known for its role in processing rewarding stimuli.

2-Minute Neuroscience: Medulla Oblongata

In this video, I discuss the medulla oblongata. The medulla is part of the brainstem and is responsible for a number of important functions. It is involved with regulating cardiovascular and respiratory functions as well as a variety of reflexive actions like swallowing, coughing, and vomiting. It is also home to an assortment of important nuclei and cranial nerve nuclei. Finally, a number of tracts like the corticospinal and corticobulbar tracts pass through the medulla on their way from the brainstem to the spinal cord and vice versa.

Know your brain: Medulla oblongata

Where is the medulla oblongata?

medulla oblongata

The medulla oblongata, often simply called the medulla, is an elongated section of neural tissue that makes up part of the brainstem. The medulla is anterior to the cerebellum and is the part of the brainstem that connects to the spinal cord. It is continuous with the spinal cord, meaning there is not a clear delineation between the spinal cord and medulla but rather the spinal cord gradually transitions into the medulla.

What is the medulla oblongata and what does it do?

For most of the 18th century, the medulla oblongata was thought to simply be an extension of the spinal cord without any distinct functions of its own. This changed in 1806, when Julien-Jean-Cesar Legallois found that he could remove the cortex and cerebellum of rabbits and they would continue to breathe. When he removed a specific section of the medulla, however, respiration stopped immediately. Legallois had found what he believed to be a "respiratory center" in the medulla, and soon after the medulla was considered to be a center of vital functions (i.e. functions necessary for survival).

Over time, exactly which "vital functions" were linked to the medulla would become more clear, and the medulla would come to be recognized as a crucial area for the control of both cardiovascular and respiratory functions. The role of the medulla in cardiovascular function involves the regulation of heart rate and blood pressure to ensure that an adequate blood supply continues to circulate throughout the body at all times. To accomplish this, a nucleus in the medulla called the nucleus of the solitary tract receives information from stretch receptors in blood vessels. These receptors---called baroreceptors---can detect when the walls of blood vessels expand and contract, and thus can detect changes in blood pressure.

When baroreceptors send signals indicating that blood pressure is deviating from a desired range, then reflexive mechanisms are enacted to return it to equilibrium. For example, when a fall in blood pressure is detected by baroreceptors, they send information regarding such a change to the nucleus of the solitary tract. The nucleus of the solitary tract then activates neurons in the ventrolateral medulla that control sympathetic nervous system innervation of neurons that increase heart rate and blood pressure. At the same time, inhibition of parasympathetic activity ensures there will not be a conflicting drive to lower heart rate and/or blood pressure. Overall, these reflexive actions ensure that critical organs like the brain will not be affected by transient fluctuations in blood pressure.

There are also neurons in the medulla that receive information from receptors called chemoreceptors, which are found within blood vessels and can detect changes in the chemical composition of the blood. These chemoreceptors can recognize changes in oxygen and carbon dioxide levels, and medullary neurons use this information to respond to oxygen need by increasing respiration. These neurons are found in and around the nucleus of the solitary tract and another nucleus in the medulla called the nucleus ambiguus. The medulla isn't only involved in adjusting respiration in response to need, however; the medulla also generates normal breathing movements by stimulating the nerve that supplies the diaphragm. This stimulation begins at around 11 to 13 weeks of gestation in humans and continues until death.

While these cardiovascular and respiratory centers are clearly what led 19th century neuroscientists to consider the medulla the center of vital functions, the full range of activities of the medulla is considerably more diverse. In addition to the reflexive cardiovascular and respiratory actions mentioned above, neuronal groups in the medulla are also responsible for other reflexive actions like swallowing, coughing, sneezing, and vomiting. Vomiting is controlled by an area of the medulla called the area postrema, which is not protected by the blood-brain barrier. This lack of blood-brain barrier protection allows neurons in the area postrema to come into contact with the blood. By doing so, area postrema neurons can detect potentially toxic substances in the blood and trigger vomiting if present.

There are a number of other important nuclei in the medulla. Several cranial nerve nuclei are found there, as well as the inferior olivary nuclei, which are densely interconnected with the cerebellum and thought to play a role in motor control. The nucleus gracilis and nucleus cuneatus are both found in the medulla; they are important nuclei along a pathway called the dorsal columns-medial lemniscus, which carries sensory information to the brain.

The medulla's position as the lowest part of the brainstem also causes it to also be a conduit for a number of tracts that pass from the spinal cord into the brainstem and from the brainstem into the spinal cord. For example, the corticospinal tract---a major descending tract for voluntary movement---passes from the medulla into the spinal cord. The corticospinal tract and another tract called the corticobulbar tract, which is involved with movement of the head and neck, form triangular bundles of fibers in the medulla that create ridges on the outside of the brainstem. The bundles and associated ridges have been termed the medullary pyramids, and the corticospinal and corticobulbar tracts are often referred to as the pyramidal tracts because of their association with the pyramids. At the junction of the medulla and spinal cord, the corticospinal tract decussates, or crosses over to the other side of the body, before continuing down into the spinal cord. The location of this decussation is referred to as the pyramidal decussation.

Thus, the medulla oblongata's functions are extraordinarily diverse and include those that are essential to life as well as to other important activities like movement. Due to its role in regulating vital functions, however, you could make the argument that the medulla is perhaps the most important area of the brain.

Kandel ER, Schwartz JH, Jessell TM 2000. Principles of Neural Science, 5th ed. McGraw-Hill, New York.

Learn more - Know your brain: Brainstem

Watch this 2-Minute Neuroscience video to learn more about the brainstem.