A neuron, which is also called a specialized cell, conducts electrochemical impulses known as nerve impulses or action potentials. It acts as the main component of the nervous system and has a critical function in integrating and transmitting electrochemical activity among other interconnected neurons. Neurons are vital structures that contribute to information processing within the CNS. In fact, the human brain can have approximately 10,000 different types of neurons.
Nerve cells consist of a body and axon branches, which are situated near neighboring nerves or muscles. The transmission of nerve impulses takes place between axons and other nerves or muscles. In cases of nerve damage, the speed of impulse transmission can decrease. The nerve is surrounded by a robust protective layer known as myelin.
Nerve damage can result in the loss or impairment of myelin, the nerve body, or the axon area. The nerve conduction study, created in the 1960s, can identify nerve function loss caused by these injuries and provide insights into the underlying issue based on the produced nerve signal pattern. The pattern of signal transmission varies depending on the type of nerve damage. In a healthy nerve cell, sensors positioned at both ends of the cell will detect an identical signal pattern.
But, when there is a blockage in a nerve cell, these sensors will detect different signal patterns. Similarly, when transmission is not fully blocked, the signal pattern at the axon may retain its shape but have reduced intensity compared to the original signal. This is because the signal is not able to complete its journey down the nerve cell entirely. The size of the response (amplitude) is primarily impacted by diseases of the nerve itself, while diseases of the myelin primarily affect the speed of the responses.
Nerve conduction studies have become a standard procedure and can be performed in almost any hospital that has the necessary equipment and qualified personnel. The study involves using a computer, computer monitor, amplifier, loudspeaker, electrical stimulator, and filters. These filters are mathematical filters designed to differentiate between random electrical signals in the background and the signal generated by a stimulated nerve. During the study, small electrodes are placed on the skin over the muscles being examined. Typically, these muscles are situated in the arms or legs.
Some electrodes record the electrical signal, while others, known as reference electrodes, monitor signal quality to ensure accurate test results. Applying a small electrical current along multiple points of the nerve, rather than just one, is necessary due to uneven impulse conduction. Proper monitoring is crucial; otherwise, the obtained results hold no meaning.
Placing stimulating electrodes at multiple sites enables a more accurate measurement of conduction velocity. This is because certain regions of a nerve may conduct slower than others. When electrical current is applied, nearby nerves, including those connected to the specific muscle, are activated. Consequently, the stimulation of these nerves generates an electric signal known as “firing.” Certain electrodes can detect this nerve signal and send it to a computer for analysis.
By examining the way in which the nerve signal travels through both the nerve and neighboring muscle, one can analyze the signal. The examiner can assess the functionality or lack thereof of the nerve by taking into account various factors including speed, shape, wavelength, and height of the signal wave.
The nervous system transmits signals via an elongated and slender cell structure known as an axon. Subsequently, the signal arrives at the presynaptic membrane where neurotransmitters are housed. These neurotransmitters are then released into a gap referred to as the synaptic cleft.
Neurotransmitter molecules that flow freely are collected by receptors, which are structures on cellular surfaces that receive specific molecules like a “lock and key.” These receptors are found in neurons, which are nerve cells responsible for transmitting messages. The nerve impulse travels from the initial neuron through its axon, a single smooth body extending from the neuron, to reach the axon terminal and synaptic knobs. The synaptic knobs in turn connect with dendrites or cell bodies of other neurons. Inside the synaptic knobs, there are neurovesicles that store and release neurotransmitters.
The synapse acts as a connection between the synaptic knob and the adjacent cell, transmitting an impulse by releasing neurotransmitters into the gap. This action stimulates the postsynaptic membrane of a nearby neuron, allowing it to receive the impulse. After being captured by receptors in this membrane, the neurotransmitter is absorbed into the neuron, promoting further propagation of the impulse. This swift process improves communication between nerve cells.
Under normal conditions, the neurotransmitter is usually released from vesicles on the presynaptic membrane and should move towards receptor sites on the postsynaptic membrane. However, certain diseases can disrupt this process. In instances of depression, there is a malfunction in serotonin movement, which is an inhibitory neurotransmitter. As a result, instead of reaching the receptors on the postsynaptic membrane, molecules return to the presynaptic membrane. This interruption impedes the transmission of impulses to neighboring neurons.
Insights into the causes of mental disorders, including clinical depression and chemical dependency, have been gained through understanding neurotransmitter function and their brain locations. This knowledge has also aided in the development of medications that enhance the proper functioning and transmission of neurotransmitters. For instance, schizophrenia, a mental illness marked by disruptions in thinking and emotional responses, is associated with dysfunction in dopamine-containing neurons in the brain.
Both chlorpromazine and clozapine are medications used to help relieve symptoms and assist patients in reintegrating into a normal social environment. These medications work by blocking dopamine receptors in the brain.
Approximately 3.5% of the population is impacted by depression, which results in irregular regulation of mood, thoughts, pain, and other sensations. In order to address depression, antidepressant medication focuses on correcting the abnormal activity of brain neurotransmitters such as norepinephrine and serotonin.
Fluoxetine (Prozac) is an SSRI medication that inhibits the reuptake of serotonin, a neurotransmitter responsible for regulating brain functioning. By doing so, it fosters regular brain activity and alleviates symptoms associated with depression. Alzheimer’s disease impacts around four million individuals in the United States, causing memory loss and impairments in self-care capabilities.
One possible cause of the disease is believed to be a reduction in cells that produce acetylcholine in the basal forebrain. These cells are responsible for processing sensory and associative information, as well as controlling motor activity. Although there are medications that can help relieve symptoms, there is currently no cure available.
Excessive worry caused by generalized anxiety disorder (GAD) impairs individuals’ ability to fulfill work obligations and carry out daily tasks. Research shows that GAD affects various neurotransmitter systems in the brain, including norepinephrine and serotonin.
ADHD individuals face challenges with attention, overactivity, impulse control, and distractibility. Research suggests a significant correlation between ADHD and imbalances in dopamine and norepinephrine neurotransmitters. Furthermore, multiple studies associate these imbalances with different disorders such as borderline personality disorder, schizotypal personality disorder, avoidant personality disorder, social phobia, histrionic personality disorder, and somatization disorder.
Both cocaine and crack cocaine are psychostimulants that affect dopamine neurons in the limbic and frontal cortex of the brain. Cocaine use produces feelings of empowerment and self-confidence, but excessive consumption results in a “crash” characterized by physical fatigue, emotional exhaustion, and depression. In contrast, opiates such as heroin and morphine appear to mimic endorphins – natural peptide substances that act as opiate neurotransmitters in the brain.
The brain naturally produces endorphins, which can alleviate pain, create pleasure, and cause drowsiness. Participating in intense aerobic exercise results in the release of endorphins, contributing to the euphoric feeling commonly experienced by long-distance runners. On the other hand, opiates such as morphine and heroin bind to the brain’s endorphin receptors and inhibit the production of natural endorphins. As a result, addiction develops as these substances become necessary to compensate for the lack of naturally occurring endorphins. To counteract the effects of these drugs, medications like nalorphine, naloxone, and naltrexone are used because they mimic their actions.
Alcohol, a depressant drug, impacts the GABA receptor and has various effects. Initially, it aids in anxiety management; however, excessive consumption hinders muscle control, delays reaction time, and impairs cognitive functions. Neurobiologists have made significant advancements in understanding how neurons regulate dendrite growth to form intricate connections with neighboring cells.
Researchers claim that dendritic connections act as the primary receptors for neurons to establish signaling networks, forming the brain’s circuitry. They argue that this knowledge will aid in comprehending child brain development and restoring lost neuronal connections caused by injury, stroke, or neurodegenerative disease.
In the December 2005 issue of Neuron, Michael Ehlers and his team found that “Golgi outposts” play a vital role in distributing the proteins needed for dendrite growth.
The Golgi apparatus is in charge of receiving, sorting, and shipping recently created molecules essential for cell growth and function. Previously, it was believed that only a central Golgi apparatus played a role in this process. Researchers used to think that in most mammalian cells, the Golgi had a stacked system structure positioned near the cell nucleus, as stated by Ehlers. However, in mammalian neurons found in the brain which are considerably larger than typical cells, the Golgi spans an area approximately ten thousand times larger.
The researchers examined the origin of membrane components responsible for the development of dendrites’ complex surface. They hypothesized that Golgi outposts, which are remote structures found in dendrites, might have a role in this process. The study focused on pyramidal neurons, which have one long “apical” dendrite and several shorter ones. To investigate the function of Golgi outposts, the researchers utilized live imaging of cultured rat brain cells and electron microscopy of rat brain tissue.
These studies found that Golgi outposts were more likely to be found in longer dendrites. The Golgi in the main cell body also showed a tendency to orient towards longer dendrites. Furthermore, studies in cell culture showed that the orientation of Golgi preceded the preferential growth of long dendrites. This discovery indicated that the presence of Golgi was not simply correlated with longer dendrites. Initially, when these developing dendrites are all similar in length, they grow at a similar pace.
The Golgi initially orients towards one dendrite and then starts to grow dynamically, eventually becoming the longest dendrite. According to Ehlers, tracer molecules were used to track the molecular cargo secreted by the Golgi. It was observed that this cargo is directed towards the longest dendrite in a highly preferential manner. The cargo does not randomly go to the cell surface as it emerges from the Golgi.
According to Ehlers and his colleagues, the Golgi outposts have been observed to position themselves at dendritic branch points. This discovery is significant because neurons face the challenge of appropriately sorting cargo molecules in different quantities along separate dendritic branches,” said Ehlers. “Considering the distinct functional properties, molecular composition, and electrical properties that can vary across dendritic branches, it becomes crucial to guide the cargo when it reaches a branch point, similar to an intersection on a highway. Our findings indicate that these dendritic Golgi outposts are strategically positioned to fulfill this role.
And I believe this is the first such specific organelle identified at a dendritic branch point positioned to perform this fundamental neuronal function. Finally, the researchers disrupted the orientation, or “polarity,” of the Golgi — thus causing them to move into all the dendrites — without disrupting their function. They found that disrupting the polarity caused all the dendrites to grow at the same rate. Further studies, said Ehlers, will explore how Golgi outposts arise, how they arrive at dendritic branch points and what cargo they distribute.
Researchers will investigate the selection and synthesis of molecules within dendrites for importation to distant regions. These studies can offer important insights into the regulation and processes of neuronal growth. Ehlers emphasizes the importance of understanding this, as abnormal dendritic structures are frequently linked to developmental disorders in children. Additionally, protein processing significantly contributes to various neurodegenerative diseases such as Parkinson’s and Alzheimer’s.
Nerve conduction is crucial for our perceptions, thoughts, and memories since it entails the transmission of nerve impulses along neurons. This process uses electricity produced by chemical molecules and is electrochemical in nature. In other words, the electrical activity in our brain is distinct from that observed in a standard household electrical wire.
The brain does not generate its own electricity. Instead, it produces electrical activity by facilitating the movement of electrically charged molecules across neuron membranes. Neurons have channels in their membranes that enable the passage of these charged molecules, similar to other cells. However, what distinguishes neuronal channels is their specific function in coordinating charge movement across the membrane to facilitate nerve impulse conduction.
The simplified diagram below illustrates the sequence of events through which a nerve impulse is conducted. By clicking on step numbers 2 and 3, you can view the corresponding steps. The scientific community possesses extensive knowledge regarding the charged molecules responsible for generating nerve impulses and their sequential movements. However, the conduction of a nerve impulse along a solitary neuron would be useless without synaptic transmission, which enables the impulse to pass from one neuron to another.
The brain’s computational abilities stem from the communication amongst its billions of nerve cells. However, for the process of neural conduction to be effective, it must be coupled with synaptic transmission. This mechanism allows a nerve impulse to pass from one neuron to another, despite the fact that the neurons do not physically touch. At the synapse, chemical messengers are secreted to regenerate the nerve impulse and facilitate communication between the neurons.
The process of synaptic transmission consists of four main steps, which can be seen by clicking on step numbers 2, 3, and 4 in the diagram below. The membrane channels are crucial in all four phases of synaptic transmission, along with the chemical messengers and receptors.
The term “synapse” refers to the point of connection between the axon of one neuron and the dendrite of another. This term originated from the Greek words “syn” meaning together and “haptein” meaning join. In the animal kingdom, neurons can be connected in two distinct ways: through electrical synapses, where the cells are physically touching and connected by small holes that allow the nerve impulse to pass directly; or through chemical synapses, where the cells are not directly in contact and specific molecules are required to bridge the gap. The majority of synapses in the human brain are chemical synapses. Although chemical synapses are slower than electrical ones, they offer greater flexibility.
The foundation of all learning lies in the valuable flexibility. While a nerve impulse in a chemical synapse can only travel in one direction, it can travel in both directions in an electrical synapse. Additionally, the transmission of the impulse across a chemical synapse is delayed by 0.5 milliseconds, whereas the delay is nearly non-existent across an electrical synapse.
Neurotransmitters are chemical molecules responsible for transmitting nerve impulses across the synapse from one neuron to another. Each neurotransmitter has a unique molecular structure that allows it to bind to specific sites on the second neuron and produce its specific effect, similar to a key fitting into a lock. Neurotransmitters are categorized based on their effects on the second neuron after being released into the synaptic gap.
Excitatory neurotransmitters aid in the propagation of nerve impulses for neurons, while inhibitory neurotransmitters hinder their propagation. The human nervous system consists of glial cells and neurons. Neurons are responsible for our intelligence. Each neuron, like any other cell in the body, has a membrane surrounding its cytoplasm and a nucleus holding its genes.
Neurons possess organelles for energy production and protein synthesis. However, what sets them apart from other cells are their specialized extensions. Dendrites collect and transmit information to the cell body, resembling tree-like structures. On the other hand, neurons have one axon, which is typically long, responsible for relaying information away from the cell body to other neurons through synapses.
Axons have the ability to directly stimulate various cell types, including muscle and gland cells. The human nervous system consists of two cell types: glial cells and neurons. Although glial cells outnumber neurons by 10 to 50 times in the human nervous system’s typical 100 billion count, they often receive little attention. This is mainly due to the fact that glial cells do not conduct nerve impulses. However, their importance should not be underestimated as they play a crucial role in facilitating the proper functioning of neurons.
The glial cells have multiple roles in supporting neurons. They nourish, physically support, and protect neurons. Additionally, glial cells help eliminate waste produced by dying neurons and enhance neural conduction by acting as an insulating sheath around specific axons. Different types of glial cells carry out each of these functions. The formation of cerebral hemispheres starts around six to eight weeks after fertilization. By the seventh week, nerves establish connections with certain muscles, enabling the embryo to make spontaneous movements.
During the eighth week, all essential internal and external structures of the body are formed. The remaining two trimesters of pregnancy are focused on the growth of these structures. Proliferation occurs in specific areas called germinal zones within the neural tube’s epithelium. The germinal zones responsible for the development of most parts of the nervous system are found near the surface of one of the brain’s ventricular system cavities.
Around three weeks after fertilization, the human brain consists of a single layer of flattened cells called the neural plate, which is located in the ectoderm. A furrow then develops in this plate, extending from the front to the back. The sides of this furrow become the neural groove. Subsequently, the sides of the groove close inward, starting from the center and moving outward towards the front and back, resulting in the formation of the neural tube. Within the dorsal part of the neural tube, specific cells will give rise to the neural crest, which is responsible for producing the neurons of the peripheral nervous system.
The neural plate differentiates into the floor plate above the notochord. The floor plate induces inductive signals that develop spinal motor neurons, as well as motor neurons of the medulla and pons from the neural tube’s most ventral cells. Sensory neurons originate from the most dorsal cells. Neurulation, the formation of the neural tube, often starts before pregnancy is recognized and is where the brain and spinal cord will develop.
During this stage, the largest organs in the embryo are formed, giving it a curved shape. By the end of the third week, the eyes and ears start to develop. Once segmentation and gastrulation are finished, the process of organogenesis begins. In this phase, groups of cells that will later become different organs in the human body are established. Organogenesis initiates with metamerization, where the mesoderm divides into identical segments known as metameres along the embryo’s longitudinal axis.
At this stage of development, the mesoderm forms somites next to the neural tube. These somites will eventually develop into the 33 vertebrae of the spinal column and the corresponding skeletal muscles. (Source: Dr. K. Tosney, University of Michigan) The neural tube fully closes at the beginning of the fourth week after fertilization, marking the completion of the first stage in the development of the brain and spinal cord. The next stage, histogenesis, where stem cells differentiate into various nerve tissues, can now commence.
Simultaneously, the brain’s major divisions develop, with cells rearranging accordingly. The encephalon takes shape as the neural tube expands and divides into the three primary vesicles (prosencephalon, mesencephalon, and rhombencephalon), and further into five secondary vesicles (telencephalon, diencephalon, mesencephalon, metencephalon, and myelencephalon).
The telencephalon is the most rostral of the secondary vesicles. Two buds emerge from either side of its rostral portion to form the two telencephalic vesicles. These two vesicles grow rapidly to form the two cerebral hemispheres. First they grow back over the diencephalon, then they grow down to cover its sides. General diagram of a sagittal section of the brain (applicable to all mammals) | Another pair of vesicles will also sprout from the ventral surface of these cerebral hemispheres to become the olfactory bulbs and other structures that contribute to the sense of smell.
The walls of the telencephalon will give rise to various structures and the white matter that connects them. The neurons in the telencephalon wall will multiply and form three distinct regions – the cerebral cortex, the basal telencephalon, and the olfactory bulb. As these neurons develop, their axons will gradually lengthen and create connections with other parts of the nervous system. Some of these axons will make up the cortical white matter, which originates from and projects to neurons in the cortex. Other axons will form the corpus callosum, a bundle of nerve fibers that links the two brain hemispheres.
Some connections within the brain, known as the internal capsule, link the cortical white matter to the brain stem via the thalamus. For example, the axons from the motor cortex pass through the internal capsule to connect with motor neurons in the spinal cord. Additionally, in the space between the telencephalon and diencephalon on both sides, the two cerebral ventricles (also called lateral ventricles or first and second ventricle) form. The third ventricle forms in the central space of the diencephalon.
The thalamus and the hypothalamus are distinct areas that develop from the diencephalon. Alongside the diencephalon, two secondary vesicles called optic vesicles also form. These optic vesicles fold inward and lengthen to create the optic peduncles and optic cups, which will eventually generate the retinas and the optic nerves. It is important to note that the retinas and the optic nerves are not part of the peripheral nervous system, but rather they are crucial components of the brain. While the telencephalon and diencephalon undergo significant changes, the mesencephalon undergoes relatively minor transformations.
The tectum is formed by the dorsal surface, while the tegmentum is formed by the floor. As these structures differentiate, the cavity that separates them becomes smaller and is called the cerebral aqueduct. The front part of this aqueduct opens into the third ventricle of the diencephalon. The mesencephalon acts as a passageway for bundles of fibers that connect the cortex to the spinal cord. These fibers include those from the sensory system and those involved in movement control. The tectum undergoes differentiation and becomes two structures.
The superior colliculus is responsible for receiving direct information from the eye and controlling eye movements. On the other hand, the inferior colliculus receives information from the ear and acts as an important relay in the auditory pathways. Located in the tegmentum area of the brain, this region is known for its vibrant colors. It houses two structures, namely the substantia nigra (referred to as “black matter”) and the red nucleus, which play a role in voluntary movement control. Additionally, various cell groups in the mesencephalon send their axons diffusely into different regions of the brain, impacting various functions like consciousness, mood, pleasure, and pain.
Located caudally to the mesencephalon is the metencephalon, which is the anterior part of the hindbrain. The metencephalon gives rise to two main structures, namely the cerebellum and the pons. The cerebellum originates from the thickened tissue that covers the lateral walls of the neural tube in this region. Eventually, these two masses merge dorsally to form the cerebellum. Concurrently, a bulge forms on the ventral aspect of the metencephalon, which develops into the pons.
The myelencephalon, which is located in the caudal portion of the hindbrain, plays a crucial role as an information pathway connecting the brain, cerebellum, and spinal cord. While the changes that occur in this region are not as remarkable, the ventral and lateral regions of the myelencephalon undergo enlargement to form the medulla oblongata. Additionally, the development of the two medullary pyramids along the ventral aspect of the medulla is observed. These pyramids are formed by the passage of corticospinal bundles that are responsible for voluntary movement. Furthermore, the central canal that persists during the formation of the medulla ultimately becomes the fourth ventricle.
The spinal cord is formed from the neural tube that is caudal to the five secondary vesicles. This transformation occurs through a process of differentiation where the walls of the tube thicken, gradually reducing its diameter until it becomes the narrow spinal canal. In the cross-section depicted here, the grey matter in the center (resembling a butterfly shape) contains the cell bodies of neurons, while the peripheral white matter consists of bundles of axons.
The spinal cord has grey matter that is divided into the dorsal horn and ventral horn. The dorsal horn receives sensory inputs while the ventral horn innervates skeletal muscles. Additionally, the white matter contains dorsal columns made up of sensory axons that go up to the brain and lateral columns consisting of corticospinal axons that go down to transmit movement control signals. Between the dorsal and ventral horns, numerous interneurons develop. These interneurons play a role in reflexes and establishing networks for processing information in the spinal cord.
A synapse is the point of connection between two neurons. However, a nerve impulse can also be transmitted from a sensory receptor cell to a neuron or from a neuron to muscles, causing them to contract, or to an endocrine gland, causing it to secrete a hormone. In these latter two cases, the points of connection are referred to as neuromuscular and neuroglandular junctions.
In a typical chemical synapse, the neuron that sends the nerve impulse is known as the presynaptic neuron, while the neuron that receives neurotransmitters is called the postsynaptic neuron. The presynaptic neuron possesses specific structures that differentiate it from the postsynaptic neuron.
The terminal button of the presynaptic neuron’s axon contains mitochondria and microtubules that transport neurotransmitters from the cell body to the tip of the axon. The button also has spherical vesicles filled with neurotransmitters. These neurotransmitters are secreted into the synaptic gap through exocytosis, where the vesicles’ membranes fuse with the postsynaptic button. (click on 2. Axonal Transport)
The synaptic gap, through which neurotransmitters must pass, is extremely narrow, measuring around 0.02 micron. Within this gap, the neurotransmitters attach to membrane receptors. These receptors are large proteins that are firmly positioned in the cell membrane of the post-synaptic neuron. By using an electron microscope, one can observe a collection of opaque material at this location, which includes a cluster of receptors and other vital signaling proteins required for chemical neurotransmission. Each neurotransmitter has various sub-types of receptors that are unique to it.
When certain sub-types of neurotransmitters are present or absent, they trigger specific chemical reactions in the postsynaptic neuron, causing it to either become excited or inhibited. An agonist is a molecule that has the same effect on the postsynaptic neuron as the neurotransmitter itself. Conversely, an antagonist is a molecule that…