Neurons 2022 Sum HP

         **Neurons and the Nervous System** *Objectives:*  * Describe the basic design and function of neurons * Tell how a neuron signals another at a synapse, and describe the possible outcomes * Know what support cells are and what jobs they do * Appropriately apply common terminology and acronyms for nervous system design and function * Identify the basic areas of the brain and their primary functions \ *A question to ponder: Is it a good trade to give up study time to exercise, if you really want academic success?* \ **Neuron design**   \ 1. The cell body of the neuron houses the nucleus and most organelles. When a neuron cell body is lost, it is unlikely to be replaced. Neurons can’t do mitosis and stem cells do not tend to replace lost neurons in adults. 2. **Processes** are where neurons reach out extensions to contact other cells 1. Each neuron has one or more **dendrites** to carry information *towards* the cell body. In the central nervous system (brain and spinal cord, **CNS**) the dendrites of a neuron are often on the receiving end of synapses (connections) with *thousands* of other neurons to form complex networks. 2. Each neuron has one **axon** to carry information *away* from the cell body towards synapses with other cells. The axon branches so it can synapse with many other cells. 3. When discussing a single neuron, dendrites are therefore the *afferent* processes, as ‘afferent’ is an anatomical term meaning ‘toward the point of reference’ which in this case is the cell body. Axons are therefore *efferent* processes, as ‘efferent’ is an anatomical term meaning ‘away from the point of reference’ which in this case is the cell body. The terms afferent and efferent do change when the point of reference changes though (as in the discussion of synapses, where the axons are afferent because they take the information towards the synapse). 4. Processes can at least potentially regrow if damaged. Regrowth is more likely in the peripheral than the central nervous system, and does not always occur. The presence of myelination (described later) encourages regrowth. 5. The diagram below shows a common look for a neuron. The long process with the blue stuff (myelination) on it is the axon; the other processes are dendrites. Some synapses with other cells are shown, as is the axon branching. Insets show a synapse and myelination; refer back here when those are discussed. Thanks for the image to By LadyofHats \[Public domain\], via Wikimedia Commons \ \  \ 3. **Synapses** are the regions where neurons communicate with other cells. The afferent (sending) sides of synapses are at the ends of axons, called *axon terminals*.         The efferent (receiving) sides of synapses are on dendrites and cell bodies. \ **Neurons signal other cells at synapses** \ 1. Synapses are the sites of intercellular communication. 2. Synapses occur where an end of an axon (the **axon terminal**) of one neuron closely approaches but does not *quite* touch the cell to which it will communicate (a dendrite or cell body of another neuron, or a muscle or gland cell).   3. ***Neurotransmitters*** (**NTs**) are chemicals that act as messengers and carry the message across the synapse. 1. A single synapse will usually use only one neurotransmitter. Reception of a given NT at *that* synapse always excite *or* inhibit the receiving cell. The choice of whether it excites or inhibits is made when the synapse is built and does not change thereafter. 2. A given NT can mean different things at different synapses: At one synapse it may excite the receiving cell, whereas at a different synapse it may be inhibitory. 3. A variety of different NTs exist. We will only name a couple in this course, including **Acetylcholine (ACh)** and **Norepinephrine (NorE).** 4. It is quite common for a single *cell* to have receptors for multiple neurotransmitters that mean different things. For example, heart cells have some receptors for the NT ACh, and activation of ACh receptors inhibits these cells; and the same cells have separate receptors for the NT NorE, and activation of these receptors excite heart cells. 4. A scheme of synaptic transmission: 1. An AP occurs in the presynaptic neuron (the one which is to send the signal, also called the afferent neuron). 2. The presynaptic neuron already contains vesicles (small membrane-bound packets) full of the neurotransmitter appropriate for this synapse. 3. The AP in the presnyaptic neuron causes those vesicles of neurotransmitter (NT) to dock, fuse, and release their NT into the ***synaptic cleft***, the small space between the cell membranes of the sending (presynaptic) cell and the receiving (postsynaptic) cell. 4. The NT binds receptors (special proteins in the cell membrane) for it located on the postsynaptic cell. 5. Binding of the NT to the receptor opens or closes gates for specific ions.  (The receptors serve as *chemical-gated ion channels*). Which ions are affected is different for different synapses. 6. Ion flow changes, initiating a GP in the efferent cell. 7. The GP will cause depolarization (called an *excitatory post-synaptic potential*) if this synapse is designed to be excitatory. **Most excitatory synapses work by increasing leakage of Na+ or Ca+2  ions,** which enter the cells to make the membrane potential less negative, or perhaps even positive. 8. If the synapse is designed to be inhibitory, the binding of the neurotransmitter will change ion flows in ways that make it *harder* to depolarize the cell to threshold  **Most inhibitory synapses work by increasing leakage of K+ (which leaks out) or Cl-** (which leaks in), or decreasing the leakage of calcium (which reduces calcium’s ability to depolarize the cell). 9. The GP causes the efferent cell to do whatever it is supposed to do in response to this signal. 10. The NT will be enzymatically broken down or shipped back into the afferent axon terminal to be recycled.This shipment back into the axon terminal is the job of the re-uptake pumps shown in the picture below. 11. There is a diagram below to show a synapse. Also, you might like to cl__[ick here](https://www.google.com/url?q=https://www.youtube.com/watch?v%3DWhowH0kb7n0&sa=D&source=editors&ust=1663284159968242&usg=AOvVaw3tUi9KW7f4wOqLiv59hGDk) to see the process in action: [https://www.youtube.com/watch?v=WhowH0kb7n0](https://www.google.com/url?q=https://www.youtube.com/watch?v%3DWhowH0kb7n0&sa=D&source=editors&ust=1663284159968557&usg=AOvVaw2iRjWw7ggqh9nVOtGF-UnF)__ \  \ 5. Whether or not the efferent (post-synaptic) cell experiences its own AP depends on the algebraic sum of all GPs currently in the cell – if the cell is excitable and its threshold membrane potential is reached, it will fire an AP. 1. Some synapses are so designed that a single receptor event in a single neuron is sufficient to cause an AP in the efferent cell. *e.g*. Motor neurons innervating skeletal muscles. One AP in the neuron causes enough NT release to cause one AP in the skeletal muscle cell. 2. Most often multiple synaptic events are needed to depolarize the efferent cell to threshold to cause it to fire its own AP. 3. Most neurons are simultaneously receiving inputs from hundreds or thousands of synapses, some excitatory and some inhibitory. The net effect of all synapses determines the firing of the neuron. \ **Regions of the nervous system** \ 1. The **central nervous system**  (**CNS**) includes the *brain* and *spinal cord*. 1. **Nuclei** are clumps of neuron cell bodies in the CNS. Nuclei are gray matter (described below). 2. **Tracts** are bundles of processes running together in the CNS. Most tracts are white matter (described below). \ 2. Regions of the brain and their functions. In general: The closer to the spinal cord, the more basic and primitive the function being controlled. Numbers in parentheses after structures refer to labels in the image below. 1.  ***Brainstem***: includes *midbrain (4), pons (5),* and *medulla oblongata (6)*. 1. Complex visceral reflexes: respiration, heart rate, blood pressure, digestion, *etc*. The **medulla oblongata** is particularly important in this. 2. Origin of many cranial nerves 3. Equilibrium and postural reflexes 4. Sleep centers 2. ***Cerebellum (8):  ***Responsible for detailing precise muscular orders 1. Balance 2. Encouraging sufficient muscle tone (the basal level of contraction when you’re not intentionally activating a muscle) 3. Coordination of complex muscle actions                         The forebrain has several important parts: 3. ***Hypothalamus (3)*** 1. Homeostatic regulation: temperature, body water, timing, metabolism, etc 2. ‘Base’ emotional and behavioral responses:  Anger, sex drive, hunger 3. Important controller of endocrine (hormonal) function by controlling the pituitary gland 4. ***Thalamus (region 2, more posterior portion)*** 1. Crude awareness of sensation: Thalamic processing is required for perception, but for precise localization or description of perceptions, further processing by the cerebral cortex is required. 2. Basic level of consciousness 5. ***Basal Nuclei (region 2, near pointer tip) ***Aid muscular control (secondary to the cerebellum) by smoothing actions and inhibiting excess muscle tone. 6. ***Cerebrum (1),*** synonym ***Cerebral cortex***  1. Sense perception: Completes the interpretation of sensory data and assigns meaning   2. Voluntary activity: Decides and initiates action.  Directs the cerebellum to detail the precise orders to be delivered to the muscles. 3. Language 4. Personality 5. Reasoning, decision-making, self-awareness, creativity, memory and other ‘higher functions’ \ By Lsanabria \[CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)\], via Wikimedia Commons \ \ \ 3. The **peripheral nervous system** (**PNS**) includes all non-brain-and-cord neural         material. The PNS includes receptor cells, ganglia, and nerves. 1. **Ganglia** are clumps of neuron cell bodies (gray matter) in the PNS – similar to nuclei of the CNS, but in the periphery. 2. **Nerves** are bundles of processes running together in the PNS.  **–** similar to tracts but in the periphery. Most nerves are white matter. Most nerves carry both sensory (afferent) and motor (efferent) processes. 1. Twelve paired (left and right) **cranial** nerves serve the head and neck.                 One cranial nerve, **Cranial X**, the **Vagus** nerve, serves the viscera. 2. Thirty one pairs of **spinal nerves** arise from the spinal cord and exit between the vertebrae to serve the lower body.         3. The ganglia in the PNS and the nuclei in the CNS house the cell bodies whose processes make up the nerves and tracts. 4)        The image below may help you understand how neurons are related to nerves, ganglia, and nuclei. There are three sensory neurons in blue (their processes are in the area labeled 7) and three motor neurons in red (with processes in the area labeled 6). The single dot on each neuron represents a cell body; the long lines are axons and dendrites. You may note the sensory neurons show long dendrites, cell bodies in a clump (labeled 8), and long axons reaching into the spinal cord (labeled 5).  The motor neurons show cell bodies in the spinal cord and long axons reaching out; their dendrites are too small to show in this diagram. 1. Label 10 indicates a nerve, since it has processes from multiple neurons and is in the periphery. 2. The ends of the three blue axons, shown near label 4, would be a tract; as they are processes traveling together in a bundle in the central nervous system. 3. Label 8 indicates a ganglion, as it is a clump of neuron cell bodies in the periphery. 4. The two red cell bodies shown just down and to the left of label 5 would be in a nucleus, since it is a clump of neuron cell bodies in the CNS. 5. Thanks for the image  to  Jmarchn (Own work) \[CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)\], via Wikimedia Commons \  \ \ 5) Summary of some nervous system definitions: \ | **Structure** | **Made up of** | **Found in** | **Myelinated?** | **Primary Function** | |----|----|----|----|----| | ganglia | clumps of neuron cell bodies, plus support cells | PNS | no | Integration | | nerves | axons and dendrites | PNS | often | Rapid transmission | | nuclei | clumps of neuron cell bodies, plus support cells | CNS | no | Integration | | tracts | axons and dendrites | CNS | often | Rapid transmission | \ \ **Support cells are underrated.** \ 1. Support cells are as numerous and important as neurons. 1. At least half of brain and spinal cord cells are support cells of one sort or another. 2. Examples include glial cells, oligodendrocytes (in the CNS), Schwann cells (in the PNS), and many others. 3. Support cells do not have action potentials or release neurotransmitters, but their functions are vital. Some of their jobs include: 1. Aiding in the transport of materials between blood and neurons. 2. Insulating neural processes to speed the movement of action potentials (Myelination, described below). 3. Assisting the neurons with metabolic processes. One very important aspect of this is the metabolism and recycling of neurotransmitters. 4. Encouraging appropriate neural development, including facilitating *neuroplasticity* (when neurons make new connections or strengthen existing ones, or lose connections that have not been in use). **This function makes support cells vital in learning, as it helps pre-existing neurons strengthen connections with one another to make circuits.** 5. Producing some neuromodulators (described below) 4. Our knowledge of support cells is not well developed, but it is a hot field. The more we learn of these cells, the more we appreciate that they are vital to neural functioning and are part of information processing, rather than being mere nursemaids for neurons. 2. ***Myelination*** is a vital job done by support cells 1. ***Gray matter*** is neural tissue that has no myelination.  1. Gray matter contains neuron cell bodies and uninsulated processes that conduct action potentials relatively slowly and usually over short distances. Many support cells are also found in the gray matter. 2. Gray matter is used primarily for ***integration*** tasks: thinking, coordinating, remembering, *etc.* 3. Most gray matter is in integration areas: nuclei and ganglia. The central part of the spinal cord is gray matter (the butterfly shape seen in a cross section of the spinal cord, such as in the diagram shown earlier), as is the outer skin of the cerebral cortex. 2. ***White matter*** is neural tissue that has been ***myelinated*** by support cells. 1. White matter is processes (axons and dendrites) of neurons that have been wrapped by support cells rich ***myelin***. Myelin is a lipid that provides electrical insulation to the process. 2. White matter has no neuron cell bodies; it is axons and dendrites from many neurons, plus the support cells that provide the myelination. 3. ***Schwann cells*** are the support cells that myelinate in the peripheral NS (so Schwann cells myelinate nerves)*.*  4. ***Oligodendrocytes*** are the support cells that myelinate in the CNS (so oligodendrocytes myelinate tracts). 5. The support cells wrap multiple layers of their myelin-rich membranes around a process to electrically insulate that region of the process. 6. Myelinating cells will insulate a portion of a process, then leave an uninsulated region called a ***node of Ranvier*** before the next myelinating cell insulates another portion of the process. See the diagram at the end of this section of notes for clarification. 7. Regions of processes that are myelinated can’t conduct APs, so the APs ‘hop’ from one node of Ranvier to the next, skipping over the insulated regions. As a result of skipping so much of the process, the AP travels *up to fifty times faster* than it does in an unmyelinated process. 8. To be specific, ions can’t cross a neuron cell membrane where it is wrapped by a myelin-rich support cell, because the nonpolar lipid repels the charged ions. Therefore, ions that enter during an action potential at one node of Ranvier diffuse under the cell membrane, very quickly depolarizing the membrane at the next node of Ranvier to threshold and generating an AP. This is faster than having to open voltage-gated ion channels along every bit of the length of the cell membrane. 9. Image of myelination below thanks to Neuron_with_oligodendrocyte_and_myelin_sheath.svg: \*Complete_neuron_cell_diagram_en.svg: LadyofHatsderivative work: Andrew c (talk)derivative work: Narayanese \[Public domain\], via Wikimedia Commons 10.  \ \ 3. **The purpose of white matter is to transmit action potentials long distances very quickly.** No integration of information occurs, as there are no synapses or neuron cell bodies; it’s all about rapid transmission. 4. Myelin sheaths also provide chemical signals that guide processes from neurons as they attempt to regrow after injury. Therefore, white matter is more successful at regenerating lost processes than is gray matter. Lost neuron cell bodies are not replaced in adults. 5. [Click here](https://www.google.com/url?q=https://www.youtube.com/watch?v%3DDJe3_3XsBOg&sa=D&source=editors&ust=1663284159984234&usg=AOvVaw3ANWgKQZdbVtophPrPxUQs) to see a nice animation of myelination and how it affects AP transmission: [https://www.youtube.com/watch?v=DJe3_3XsBOg](https://www.google.com/url?q=https://www.youtube.com/watch?v%3DDJe3_3XsBOg&sa=D&source=editors&ust=1663284159984554&usg=AOvVaw18d_vOcOsuE7Ud7NyyKlqS) 3. Other signaling molecules, many from support cells, increase the complexity of signaling between neurons. 1. ***Neuromodulators*** are chemical messengers released by one cell that affect how strongly a particular synaptic activation will affect the target cell. Neuromodulators differ from neurotransmitters in multiple ways: 1. Neuromodulators can be released by neurons, but they *may also be released by support cells* which are not excitable cells. 2. Neuromodulators aren’t just released from an axon terminal, crossing a single synapse to affect receptors only on the efferent cell. They are more generally released into the interstitial fluid that surrounds the cells, so may affect multiple synapses.   3. There are many different modulators and they act in many different ways; a good description is beyond the time constraints of this course. To give you an example though: A chemical signal that caused the efferent cell to put out a different number of receptors for the neurotransmitter used in a synapse would be a neuromodulator, since it would affect how much firing of an afferent cell altered the behavior of the efferent cell. 2. Other signaling molecules, from neurons or support cells, have a complex variety of jobs. Some popular actions are encouraging or discouraging synaptic formation. For example, a chemical called ***brain-derived neurotrophic factor (BDNF)*** is released from support cells in response to exercise, and acts to encourage production of new neurons and survival and increased synapse formation of existing neurons. Thus, exercise helps you learn, because it provokes support cells to release more BDNF in any nuclei that are used a lot during or in the hours after the exercise. \ **Neuronal connections result in the development of circuits** \ Just as billions of individual on/off switches in a computer are activated in complex ways to perform a vast array of functions, billions of individual neurons having or not having APs are activated in complex ways to direct most bodily functions. 1. Some of these circuits, such as the reflex pathways, are genetically pre-programmed and the same in all neurotypical individuals. 2. Other circuits develop during a person’s lifetime (we always remodel; and we remodel in response to recent stresses -- a recurring physiological theme). Much of what we call “learning” arises by the mechanism of circuit creation and modulation. Support cells and neuromodulators affect circuit remodeling 3. Fascinating as this topic is, we haven’t time in this course to deal with it in more depth. *A question to ponder: Is it a good trade to give up study time to exercise, if you really want academic success?* Yes. Students who had a vigorous exercise class just before their hard math course learned the math better than students who had the exercise class after, for example. The brain-derived neurotrophic factor released by the exercise was thought to be the reason. \ **Key points for neurons and CNS:** \ 1. Neurons have one cell body but multiple processes. Dendrites collect information, axons carry signals to other cells. Processes may be replaced but not cell bodies. 2. Support cells are at least as abundant as neurons. They protect the neurons, provide metabolic support, insulate processes to speed transmission, and affect the way neurons connect and react when their synapses are activated, among other jobs.   3. Gray matter is for integration, the processing and storage of information. Nuclei and ganglia are composed of gray matter. White matter is myelinated so it can be used for rapid long distance transmission of action potentials. Most nerves and tracts are myelinated but nuclei and ganglia never are. 4. Neurotransmitters carry signals from one cell to another at synapses. The AP in the afferent cell causes NT to be released; it crosses the synaptic cleft, binds to the efferent cell, and causes the efferent cell to have a pre-programmed response. 5. The efferent cell may well have thousands of other synapses (from other neurons).  The efferent cell will fire its own action potential (if it is excitable) whenever the sum of all the ion leaks from all the active synapses brings the efferent cell to threshold. 6. Many chemicals other than neurotransmitters play roles in nervous system signaling, adaptation, and action. This is a complex and evolving story, currently poorly understood. 7. Know the regions of the CNS and their functions to the level of detail shown in the Regions of the Brain section. It’s already quite summarized. \ \ \