2-Minute Neuroscience: Long-Term Depression (LTD)

Long-term depression, or LTD, is a process by which synaptic connections between neurons are weakened. Although the functions of LTD are not completely understood, it may be important to memory formation---perhaps by resetting previous synaptic changes to allow for new memories to be formed via long-term potentiation (LTP). In this video, I discuss the best understood mechanism underlying LTD, which involves AMPA and NMDA glutamate receptors.

Know your brain: Telencephalon

Where is the telencephalon?

The telencephalon highlighted red. The telencephalon not only includes the cerebral cortex (visible here) but also a large number of subcortical structures, pathways, etc.

The telencephalon is also known as the cerebrum, and it consists of the largest part of the brain (it makes up about 85% of the total weight of the brain). It contains the cerebral hemispheres, and thus includes the cerebral cortex and a number of other structures lying below it (subcortical structures), along with a variety of important fiber bundles like the corpus callosum. The inferior boundaries of the telencephalon are found at the diencephalon (e.g. thalamus and hypothalamus) and the brainstem. Posteriorly, it is bordered by the cerebellum.

What is the telencephalon and what does it do?

The telencephalon begins to emerge in embryonic development at about 5 weeks. At this time, the nervous system consists of tube-shaped piece of tissue called the neural tube. The neural tube begins to develop swellings (called vesicles) that will later develop into important structures in the nervous system. The swelling that forms at the farthest end of the neural tube is called the telencephalon (telencephalon is Greek for "far brain"). 

As development continues, the growth of the telencephalon far outpaces the growth of the other structures of the nervous system. The telencephalon begins to expand into two symmetrical structures that sit alongside one another at the very end of the neural tube; these will become the cerebral hemispheres. Initially, the surface of each cerebral hemisphere is smooth, but over the course of neural development it becomes more convoluted until it takes on the appearance of an adult brain with its many sulci and gyri. Thus, the cerebral cortex is part of the telencephalon---as are all of the divisions of the cerebral cortex like the prefrontal cortex, motor cortex, somatosensory cortex, occipital cortex, and so on. 

In addition to the cortex and its recognizable features, there are a large number of subcortical structures that are considered part of the telencephalon. These include the hippocampus, amygdala, and a majority of the regions included in the basal ganglia, among others. Also a multitude of major pathways traverse the telencephalon, such as the corpus callosum---a large bundle of fibers that connects the two cerebral hemispheres---and the internal capsule---another prominent collection of neurons that carries almost all information to and from the cerebral cortex.

The telencephalon is too large an area of the brain to try to link it with a function or short list of functions. It plays a role in most of our brain activity and thus is more analagous to an entire division of the nervous system than to a particular delimited brain structure.

References:

Haines DE. Fundamental Neuroscience for Basic and Clinical Applications. 4th ed. Philadelphia, PA: Elsevier; 2013.

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

History of neuroscience: Julien Jean Cesar Legallois

The idea that different parts of the nervous system are specialized for specific functions has been a pervasive concept in brain science since ancient times, perhaps best exemplified by the belief---dating back to the 4th century CE---that the four cavities of the brain known as the ventricles each were responsible for a different function, e.g. perception in the two lateral ventricles, cognition in the third ventricle, and memory in the fourth ventricle. By the early 1800s, however, there was still no definitive experimental evidence linking a particular function to a circumscribed area of the brain.

Image showing the medulla oblongata, the region of the brainstem that Legallois found was essential to respiration.

Image showing the medulla oblongata, the region of the brainstem that Legallois found was essential to respiration.

This changed with Julien Jean Cesar Legallois, a young French physician who was driven to identify the parts of the brain and body that were essential for maintaining life. The thinking at the time was that the heart and brain were both integral to life, but there was some debate about where the life-sustaining centers in the brain were located. Some, for example, considered the cerebellum to be the organ that controlled vital functions like heartbeat and respiration. Research conducted in the second half of the 18th century by the French physician Antione Charles de Lorry, however, had suggested that the area of the brain most critical to life was found in the upper spinal cord. Legallois would take Lorry's research a step further by conducting a series of gruesome experiments with rabbits that would help him to specifically pinpoint the center of vital functions in the brain.

Before detailing these experiments, it's important to mention that Legallois' studies were done at a time when the ethical treatment of animals in research---and indeed ethics in research at all---were not given much thought. Legallois was a vivisectionist, meaning that he performed surgery on living animals in his experiments. Legallois' work would not be likely to be approved by a university or research institution today, and indeed when you read Legallois' own impassive descriptions of his grisly experiments they sound like something a budding serial killer might have dreamed up before he moved on to human victims. But this was a different time, when thoughts about animal welfare were not as well formulated as they are now---and Legallois was far from the only vivisectionist of his day. Indeed, a great deal of our current neuroscience knowledge was developed using experimental methods we would consider unjustifiably cruel today. 

Legallois' method of exploring the centers of vital functions in the brain primarily involved the decapitation of rabbits. Legallois observed that after a decapitation made at certain levels of the brainstem, the headless body of a rabbit could still continue to breathe and "survive" for some time (up to five and a half hours according to Legallois). Decapitation further down the brainstem, however, would cause respiration to cease immediately. This observation was in agreement with Lorry's. Legallois then set out to isolate the particular part of the brainstem where these respiratory functions were located.

To do this, Legallois opened the skull of a young rabbit (while the rabbit was still alive), and began to remove portions of the brain---slice by slice. He found that he could remove all of the cerebrum and cerebellum and much of the brainstem, and respiration would continue. But, when he reached a particular location in the medulla oblongata---at the point of origin for the vagus nerve---respiration stopped. Thus, Legallois surmised that respiration did not depend on the whole brain but on one circumscribed area of the medulla. He concluded that the "primary seat of life" was in the medulla, not the cerebellum or cerebrum.

Legallois published the details of his seminal experiment in 1812. We now consider the medulla to be a critical area for the control of respiration as well as the regulation of heart rate, and the region is often considered to be a center of vital functions in the nervous system. Indeed, Legallois was influential in establishing the hypothesis that the brain is involved in the regulation of heart rate as well (prior hypotheses had emphasized the ability of the heart to act alone---without the influence of the brain). While Legallois was not the first to hypothesize that vital functions are localized to the medulla (he was preceded by Lorry), he was the first to provide clear experimental evidence linking the medulla to such functions, and he greatly refined Lorry's estimation of where the vital centers were located. In the process, Legallois gave us our first clear evidence that linked a function to a localized area of the brain.

Cheung T. 2013. Limits of Life and Death: Legallois's Decapitation Experiments. Journal of the History of Biology. 46: 283-313.

Finger, S. 1994. Origins of Neuroscience. New York, NY: Oxford University Press.

For more about the medulla oblongata's role in vital functions, read this article: Know your brain - Medulla oblongata

History of neuroscience: Charles Scott Sherrington

sherrington.jpg

To many, Charles Scott Sherrington is best known for providing us with the term synapse, a word we still use to describe the junction where two neurons communicate. While Sherrington's work to understand synapses and neural communication was important, however, his studies of reflexes, proprioception, spinal nerves, muscle action, and movement were much more expansive and probably even more influential.

Regardless, his observations concerning synapses are representative of the meticulous care with which he investigated and made deductions about the nervous system and its function. His writings on the synapse came at a time when Santiago Ramon y Cajal was beginning to convince the scientific community that the brain consists of separate nerve cells (which became known as neurons in 1891) rather than a continuous "net" of uninterrupted nerves. One thing missing from this theory was an understanding of how neurons might communicate with one another.

In writing on that issue, Sherrington proposed a specialized membrane---which he termed a synapse---that separates two nerve cells that come together. Microscopes of the day couldn't actually observe the separation found at synapses (which is minutely small), so Sherrington was forced to describe the synapse as a purely functional separation---but a separation nonetheless. He based his hypothesis on observations he made in his own research like the fact that reflexes (which he studied extensively) weren't as fast as they should be if they involved simply conducting signals along continuous nerve fibers. Sherrington had originally planned to use the term syndesm to describe the functional junction between neurons, but a friend suggested synapse, from the Greek meaning "to clasp," since it "yields a better adjectival form." 

Thus the term synapse was born, but for Sherrington his observations about the synapse were really just one part of a much greater investigation into reflexes and nerve-muscle communication. He made an important contribution in this area when he helped to elucidate the mechanism underlying the famous knee-jerk reflex (which you've likely experienced when a doctor has tapped just below your kneecap to cause your leg to kick outwards).

His work on spinal reflexes also led Sherrington to another seminal hypothesis. He proposed that muscles don't just receive innervation from nerves that travel to them from the spinal cord but that they also send sensory information about muscle length, tension, and position back to the spinal cord. Sherrington believed that this information is important for things like muscle tone and posture. He hypothesized that there are receptors in the muscle that convey this type of information, and he specifically identified muscle spindles and golgi tendon organs as potential receptors that send information about stretch and tension, respectively (this would later be confirmed). To describe the information these muscle receptors send, Sherrington coined another termproprioception. He chose this term because proprius is Latin for "own" and he wanted to emphasize that the sensory information sent from these muscle receptors comes from an individual's own body, and is not initiated by an external stimulus (as is common with other receptors).

Among Sherrington's many other contributions to understanding movement and muscle function, he also helped to develop a better understanding of the mechanism underlying something called reciprocal innervation. Reciprocal innervation refers to the way in which the activation of one muscle influences the activity of other muscles. This is a common and necessary response. As we walk across the floor, for example, when the muscles involved in the extension of one leg are activated, the muscles involved in the retraction of that same leg must be inhibited. Otherwise, our muscles would constantly be competing with one another, which would result in complete rigidity and make movement (or even standing in one place) impossible. Sherrington didn't discover the phenomenon of reciprocal innervation, but he spent years studying it and in the process gave us a better understanding of how it works. His investigations of reciprocal innervation led to a number of experiments on complex reflexes involved in movements like walking, running, and even scratching. His work helped us to understand how some reflexes involve chaining together several simple reflexive actions to create a seemingly complicated behavioral display.

Sherrington's focus on spinal nerves and reflexes led him to map the motor nerves traveling from the spinal cord to the muscles and the sensory nerves traveling from the muscles to the spinal cord---a task which took him almost ten years. He also explored the functionality of these nerves, helping to create a map of the area of the body served by a single spinal nerve (areas known as dermatomes). And he mapped the ape motor cortex, expanding on previous maps that had been made with dogs and monkeys.

Thus, although Sherrington may be best known for his naming of the synapse, his other work---which was broad but focused a great deal on muscles, movement, and reflexes---was probably even more valuable to our overall understanding of the nervous system. Sherrington won the Nobel Prize for Medicine in 1932 just as he was entering into his retirement, as recognition for his wide-ranging contributions to neuroscience. He continued to write into retirement, and branched out from scientific writing to publish a collection of poems as well as a book that focused on philosophical themes like the relationship between the mind, brain, and soul. He died in 1952 at the age of ninety-five.

Finger S. Minds Behind the Brain. New York, NY: Oxford University Press; 2000