It’s about time I posted a new educational post. This will be part of a new series called “Introduction to Neuroscience”. I realize that it’s not the most creative title, but this will do for now.
Here’s what to expect in this lesson:
- A Brief History of the Brain
- Anatomy of the Brain and the Nervous System
- Basics of the Neuron
- Neuromodulators and Neurotransmitters
- Action Potential
- Glial Cells
- Endocrine System
Without further ado, let’s delve right into it.
It might seem obvious to you, but the brain is undoubtedly one of the most important organs in our body. But did you know that the brain was once thought to be just an ordinary organ with no important purpose? The ancient Egyptians used to preserve organs in canopic jars, to take with their corpses in the afterlife. The heart was the most important organ, while when the body was being “cleaned” for organs,
the Egyptians would take the brain out through the nose and discard it. During prehistoric times, trepanation, a form of primitive brain surgery involving a hole through the skull was widely practiced, believed to treat headaches, mental illness, etc. It wasn’t until the Ancient Greek period that there began to be some dispute. Alcmaeon, an early Greek physicist concluded from his studies that the brain was the central organ of the body. However, Aristotle believed the heart was the organ of thought and sensation, and (ironically) the brain was just a regulator that cooled it. It was from that moment onward that the brain became more interesting to human beings, and hence, the field of neuroscience (among many other brain-related fields) was born.
The basic anatomy of the brain and the nervous system is actually rather simple. Some of them are really simple– the frontal lobe… It’s bound to be at the front of the brain. Others are a little bit more tricky– where’s the parahippocampal gyrus again? But today, we’ll only be covering the essential basics, and we’ll get back to the complicated parts later.
Cerebrum: The largest part of the human brain, is associated with higher order functioning, including the control of voluntary behavior. Thinking, planning, understanding language is all under the cerebrum’s control. It is divided into 2 hemispheres– the right hemisphere, and the left hemisphere. The corpus callosum is a bundle of fibers that bridges the two hemispheres, and is important for the hemispheres to communicate.
Cerebral cortex: The covering of the outermost layer of the cerebrum, almost like a sheet of tissue. It has a grayish color in appearance, leading it to be often called gray matter. The cerebral cortex also provides a wrinkled appearance for the brain, over which two-thirds of the layer is folded into grooves (sulci and gyri). These grooves actually increase the brain surface area, which is beneficial– there’s more room for neurons! The cerebral cortex can be divided into the 4 lobes that we may or may not be familiar with.
Frontal Lobe: Responsible for initiating and coordinating motor movements, cognitive skills (planning, problem solving, organizing, etc).
Parietal Lobe: Involved with sensory processes, attention, and language. If the right side is damaged, the individual will have difficulties navigating spaces, no matter how familiar. If the left is damaged, the ability to understand language overall may be affected.
Occipital Lobe: Responsible for processing visual information, which includes recognition of colors and shapes. At the back of the head, funnily enough.
Temporal Lobe: Involved in processing auditory information and also integrations information from the other senses. Scientists believe that this lobe may have a role in short term memory via its hippocampal formation, and in learned emotional responses via the amygdala.
All of the above make up the first section of the anatomy, the forebrain. It’s the largest. Other important parts of the forebrain include the basal ganglia, which is cerebral nuclei deep in the cerebral cortex, thalamus, and hypothalamus.
Basal ganglia: Help coordinate muscle movements and reward helpful behaviors.
Thalamus: Passes most sensory information to cerebral cortex.
Hypothalamus: Control center for sleep-wakefulness, appetites, as well as defensive and reproductive behaviors.
The midbrain consists of two pairs of small hills called colliculi. The collections of neurons play an important role in visual and auditory reflexes and in relaying the information to the thalamus. It also has clusters of neurons that regulate activity over the CNS.
The hindbrain contains the pons, medulla oblongata, and cerebellum. These control respiration, heart rhythms and blood sugar (glucose) levels.
Cerebellum: Very similar to cerebrum, has two hemispheres which help control movement and cognitive processes requiring your time. It is important to Pavlovian learning.
The spinal cord is the extension of the brain via the vertebral column.
The Central Nervous System (CNS) consists
of the brain and spinal cord, and is one of two great division that define the nervous system. The skull protects the brain, while the spinal cord is protected by the vertebral column (around 17 inches).
The other nervous system is the Peripheral Nervous System (PNS), which consists of nerves as well as small concentrations of gray matter called ganglia. Overall, the nervous system, is a vast biological computing device formed by q network of gray matter regions interconnected by white matter tracts.
The brain sends messages via the spinal cord to peripheral nerves all throughout the body that control the muscles and internal organs. The PNS can be split into 2 branches: somatic and autonomic nervous systems. The somatic nervous system is made up of neurons connecting the CNS with parts of the body that interact with the outside world. Somatic nerves in the cervical section relates to the neck and arms; those in the thoracic serve the chest; those in the lumbar and sacral regions interact with the legs. The autonomic nervous system is made of neurons connecting to internal organs, and is once again, split into 2 parts: sympathetic and parasympathetic nervous systems. The sympathetic nervous system uses energy and resources during times of stress, fear, and arousal, activating a fight-or-flight response. The parasympathetic is just the opposite– it conserves energy and resources during relaxation, such as sleep.
The most important player in this field? Neurons. The mammalian brain contains between 100 million and 100 billion neurons, depending on the species. Each mammalian neuron has a cell body (soma), dendrites, an axon, axon hillock, dendritic spines, myelin sheath, Nodes of Ranvier, and presynaptic terminals. The cell body contains the nucleus and cytoplasm. The axon extends from the cell body and end at the axon terminals. Dendrites (in greek: tree) branch out from the cell body and receive the messages. Synapses are the specific contact points where neurons communicate with each other. When neurons send/receive messages, they also end up transmitting electrical impulses along their axons. When these axons have a myelin sheath, they go faster, since the myelin sheath insulates them and accelerates the transmission of electrical signals. The Nodes of Ranvier allow the signals to hop down the neuron, giving rise to the phenomenon termed “saltatory conduction“. Only cells with a myelin sheath can perform saltatory conduction. The myelin sheath is made by specialized support cells called glial cells (or just glia). In the brain, the glia that form the sheath are known as oligodendrocytes, but in the PNS, they are known as Schwann cells. There are much more glia than neurons, in fact, around 10 times more. Glia serve to transport nutrients to neurons, clean up brain debris, digest the parts of dead neurons, and help support the neuronal position.
So, what is the action potential? Well, to start off, nerve impulses involve opening and closing of ion channels. These, in particular, are selectively permeable, water filled molecular tunnels that pass through the cel membrane and allow ions (electrically charged atoms; small in size) to enter or leave freely. The flow of these ions creates an electrical current which causes a small voltage change across the neuronal cell membrane. These channels are the Sodium-Potassium (Na+/K+) pumps.
When it begins, a dramatic reversal occurs: the neuron switches from a internal negative charge (~-70mv) to a positive charge state, and reverses again. It causes almost a ‘spike’, if you can visualize it. This spike is called the action potential. I won’t delve too much into detail (that’s for a later post), but for now, an image should do a lot of explaining. The action potential is the reason that a neuron can possibly fire impulses multiple times every single second.
When these changes finally reach the end of the axon, they trigger the release of neurotransmitters, the brain’s chemical messengers. They are released specifically at nerve terminals, then diffuse across the synapse, and bind to receptors on the surface of the adjacent cell (usually neuron, but it could also be a muscle or gland cell!) . Each receptor is distinctly shaped that recognizes a specific neurotransmitter, almost like a lock and key! (There’s actually a model on this.) Understanding neurotransmitters is essential to understanding the circuits responsible for unfortunate disorders such as Alzheimer’s and Parkinson’s.
The first neurotransmitter to identified (around 80 years ago) was Acetylcholine (ACh). This neurotransmitter is released by neurons connected to voluntary muscles, causing contraction, and also by neurons responsible for heartbeat. It’s also in many regions of the brain. It’s synthesized in axon terminals. ACh on voluntary muscles causes muscles to contract. Acetylcholine is broken down by acetylcholinesterase and is re-synthesized in the nerve terminal. It is extremely important, and is important to activity in general. This is characterized especially in an example where they are blocked: myasthenia gravis. This disease often shows fatigue and muscle weakness in individuals. Acetylcholine is probably critical for attention, memory, and sleep. Acetylcholine releasing neurons actually die in Alzheimer’s patients, therefore drugs that inhibit acetylcholinesterase (hence increase ACh) are some of the drugs used for treatment.
Amino acids are everywhere. They’re the building blocks of proteins, after all! Sometimes, they can serves as neurotransmitters. For example, the neurotransmitters glycine and gamma-aminobutyric acid (GABA) inhibit the firing of neurons. The activity of GABA is increased by benzodiazepines (such as Valium) and anticonvulsant drugs.
For example, in Huntington’s disease, the GABA producing neurons in brain centers that coordinate movement begin to degenerate, causing uncontrollable movements, that characterize the disease.
On the other hand, glutamate and aspartate are excitatory signals, which activates N-methyl-d-aspartate (NMDA). NMDA has been implied to be in activities such as learning and memory to development and specification of nerve contacts. The stimulation of these NMDA receptors as a result may have beneficial changes, but as always, overstimulation is not good– it may cause cell death or damage.
Catecholamines includes the neurotransmitters dopamine and norepinephrine . Dopamine is directly involved in 3 circuits.
- Dopamine circuit #1 that regulates movement is evidently linked to Parkinson’s disease. In Parkinson’s, there is a dopamine deficiency. This causes tremors, rigidity, and difficulty in movement. Administration of levodopa, a substance from which dopamine is synthesized, has been proven to be an effective treatment for Parkinson’s, in addition to Deep Brain Stimulation (another interesting topic).
- Dopamine circuit #2 that’s important for cognition and emotion– this time, there’s an overabundance. Abnormalities in this system has been implicated in schizophrenia. As a result, drugs that block specific dopamine receptors in the brain actually help in diminishing psychotic symptoms. Understanding dopamine is crucial to mental illness.
- Dopamine circuit #3 that regulates the endocrine system– it’s a crucial player. Dopamine directs the hypothalamus to create hormones and store them in the pituitary gland for eventual release into the bloodstream or to trigger the release of hormones held within the pituitary.
Deficiencies in norepinephrine occur in patients with Alzheimer’s, Parkinson’s and Korsakoff’s Syndrome, which is a cognitive disorder associated with chronic alcoholism. Interestingly, they all often lead to memory loss and a decline in cognitive functioning. Perhaps it plays a role in learning and memory as well? Norepinephrine is also secreted by the sympathetic nervous system to regulate heart rate and blood pressure, especially from acute stress. Acute stress increases its release from sympathetic nerves and the adrenal medulla, which is the innermost part of the adrenal gland.
Serotonin is another important neurotransmitter, present not only in the brain, but also in other tissues, especially blood platelets and the lining of the digestive tract. It is especially important in sleep quality, mood, depression, and anxiety. Since it controls different switches, these can be manipulated by analogs, which are chemicals with molecular structures similar to that of serotonin. There are drugs that can alter serotonin’s action, such as fluoxetine (Prozac) which relieve symptoms of depression and OCD.
Peptides are short chains of amino acids linked together, and are synthesized in the cell body. In 1973, scientists found receptors of opiates on neurons in regions of the brain, which means the brain might make similar substances. They found it shortly after– the chemical resembles morphine, used to medically kill pain. They named it “enkephalin“, literally meaning “in the head”. Other types of opioid peptides were found later: endorphins, for example. They’re released in times of stress to minimize pain. Some sensory nerves (tiny un-myelinated C fibers) contain a peptide called Substance P, the principle substance causing the sensation of burning pain. It’s no surprise that it’s found in capsaicin and chili peppers then!
Trophic factors are small proteins in the brain, but don’t underestimate it for its size. They are essential for the development, function, and survival of neurons. Knowledge on trophic factors have proven useful in designing new therapies for neurodegenerative disorders.
The endocrine system is the 2nd largest communication system after the nervous system. Instead of neurotransmitters, it’s hormones! The pancreas, kidneys, heart, adrenal glands, gonads, thyroid, parathyroid, thymus and even fat are all hot spots and sources of hormones. It’s important because it acts on the pituitary gland in the brain. The pituitary gland secretes factors in the blood to act on the endocrine glands to either increase or decrease hormone production. This phenomenon is known as feedback loop. It involves communication between the two back and forth, and is responsible for the activation of basic behavioral activities such as sex, emotion, eating, etc. It’s also important to the regulation of body functions such as growth, reproduction, energy use, and metabolism. This proves that the brain is malleable and capable of responding to environmental signals, an evolutionary adaption.
In response to stress and environmental changes in our biological clocks (day and night circles and jet lag, for example), hormones enter the blood and travel everywhere. The brain adjusts its performance as a result. This is why it’s malleable. However, severe and prolonged stress can actually impair the ability of the brain to function normally, but it can also make an incredible recovery.
The brain contains receptors for thyroid hormones and the six classes of steroid hormones, synthesized from cholesterol:
- vitamin D
The brain also has receptors for:
- metabolic hormones such as insulin
- insulin like growth factor
These are fairly important since they’re taken up from the blood and act to affect neuronal activity and some aspects of neuronal structure.
Reproduction in females is a great example of a cyclic and regular process lead by hormones within a feedback loop. Neurons in the hypothalamus produce gonadotropin-releasing hormone (GnRH), which is a peptide that acts on cells in the pituitary. In BOTH males and females, this creates the hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to be released into the bloodstream. From here, the track between male and female splits. In females, these hormones act on the ovary to stimulate ovulation, promoting the release of the hormones estradiol and progesterone. In males, the hormones go to the testes, promoting spermatogenesis and release the male hormone, androgen, into the bloodstream. These hormones mentioned, as a result, are referred to as sex hormones. The increased levels of the newly release hormones decrease the release of FSH and LH, continuing the feedback loop of control. Don’t underestimate these hormones– sex hormones are also important for attention, motor control, pain, mood, and memory.
Another interesting find is that there are actually anatomical differences between the brains of heterosexual and homosexual men. Perhaps these hormones and genes act on early in life to lead to these differences?
Oh! I nearly forgot. There’s actually a new class of neurotransmitters, and they’re gases. That’s right– nitric oxide and carbon monoxide are different. They aren’t stored in vesicles, but are made by enzymes when they are needed and are released by diffusion. They just diffuse into the next neuron and act upon their targets, which could be enzymes. The exact function for carbon monoxide hasn’t been determined yet, but we have for nitric oxide. Nitric oxide governs erection in the penis, and in the intestine, it governs the relaxation that causes normal movements in digestion. In the brain, it regulates the intracellular messenger molecule cyclic GMP. In stroke (as result of excess glutamate release), neuronal damage that occurs may be attributed to nitric oxide.
The brain also derives signals from lipids. Prostaglandins are a class of compounds made from lipids by an enzyme known as cyclooxygenase. These are very small and short lived, but are strong– they can induce a fever and can cause generation of pain in response to inflammation. Aspirin reduces fever and pain by inhibiting the enzyme. The brain’s own marijuana is known as endocannabinoids, essentially cannabis by the brain. They control the release of neurotransmitters (usually inhibiting) and can affect the immune system. These, like the opioid-like morphines, increase in the brain during times of stress.
Substances that continue to communicate after the action of neurotransmitters are called second messengers. They may last from a few milliseconds to minutes. They may also cause long-term changes in the nervous system. An example of this involves the activation of adenosine triphosphate, or ATP, the chemical source of energy in all cells. When norepinephrine binds to its receptors on the surface of the neuron, the activated receptor binds a G protein on the inside of the membrane. This G proteins causes the enzyme adenylyl cyclase to convert the ATP into cyclic adenosine monophosphate (cAMP), which is the second messenger! cAMP may cause a change in the function of ion channels to the expression of genes in the nucleus itself. Second messengers may play a role in the manufacture and release of neurotransmitters and in intracellular movements and carbohydrate metabolism. They are also involved in growth and development processes. If their strength is just strong enough, they might even lead to changes in behavior.
Next up on “Introduction to Neuroscience”? Embyronic development of the brain.