Neuro MNTS Notes 2025 PDF

Course : Neuro The Medical Note-Taking Service Lecturer : Ullman Date : 08/26/2021...

Course : Neuro The Medical Note-Taking Service Lecturer : Ullman Date : 08/26/2021 Lecture Number: 45 Class of 2025 Page 1 of 8 NOTICE &DISCLAIMER Note-Taker: Ryan Greguske The Medical Note-Taking Service makes every effort to provide accurate class notes. However, errors will occur from time to time. The user Corrected by: uncorrected assumes the risk for any and all errors. We recommend that you use these notes as a supplement to your own notes. Approved for distribution: yes Greetings once again, everybody! Dr. Ullman kept this lecture straightforward, so I will do the same with the MNTS, primarily following the outline he provided on slide 4. Per usual, I have incorporated some questions in red as well as bolded/highlighted HY information. LO’s as always are clumped here, and I encourage you (and Dr. Ullman recommended!) to refer back to these objectives throughout MNTS/lecture reviews to ensure you are understanding the information as a whole and not just memorizing individual components. It’s kind of like the brain – it’s useless if we just memorize/consider individual components, but when we think of it as a whole and the connections between respective parts then we’re really functioning. (I admit the analogy was a bit lame but I hope it adds some perspective!) LO #1: Describe and understand the basic functions and organization for the nervous system, including the CNS and PNS LO #2: Know some important CNS and PNS illnesses, as presented in lecture LO #3: Understand neurons, including how they work together to underlie behavior LO #4: Know the basic structural, directional, and functional classifications of neurons LO #5: Know and understand the different types of glial cells and their basic functions LO #6: Understand the difference between gray and white matter Dr. Ullman started off with some context regarding why understanding neuroscience is important, and how it manifests as neurological and mental disorders that affect the nervous system. Dr. Ullman notes he will continue to repeat important information (repetition!) throughout the lecture (spacing effect!). The Nervous System, which Dr. Ullman functionally defines as the “system that underlies behavior and transmits information between parts of the body” is organized into two parts: the Central Nervous System (CNS) and Peripheral Nervous System (PNS). I’ve highlighted and bolded these here because it is important, throughout the lecture, to understand not only the components of each but also how they differ structurally and functionally. Q. What makes up CNS? Braint spinalcord CNS A. The brain and spinal cord! Broadly, the CNS “integrates and controls information (i.e. cognitive, sensory, motor) in the nervous system.” The Brain (CNS) Q. What are the four main, anatomical regions of the brain? A. Cerebrum, Diencephalon, Brain Stem, Cerebellum INSERT JOKE HERE  Course Neuro Lecturer Ullman Date 8/26/21 Lecture 45 Page 2 of 8 Let’s explore these four parts a bit further. -Cerebrum – cortex (the “rind” or covering) and subcortical structures (i.e. basal ganglia, amygdala). -Diencephalon – thalamus and hypothalamus -Brain Stem - midbrain, pons, and medulla oblongata. -Cerebellum – latin for “little brain” On a very simplified level, different structures and regions of the brain underlie different functions. But, it’s a bit more complicated than that simplification. For example, Dr. Ullman pointed out: Broca’s area – on a simplified level, Broca’s functions in speech control. Q. However, is it the case that Broca’s area (and other brain regions) has only one underlying function? A. No! Dr. Ullman pointed out that Broca’s area is also important for memory, for example. Again this is just one example and the take-home point is: functions of the brain depend on networks of structures that kitten work together, and are not just controlled by a single anatomical location. This will be reinforced throughout lecture. FEET Spinal Cord (CNS) – divided into Cervical, Thoracic, Lumbar, Sacral, and Coccygeal vertebra. Looking at a cross section, we can see: -afferent (aka sensory) information (INCOMING to the CNS from the PNS) enters dorsally and -efferent (aka motor) information (EXITING the CNS to the PNS) exits ventrally. *Don’t get bogged down by the anatomy here, but understand afferent vs. efferent (reinforced more later!) Afferent motor sensory CNS Efferent dorsal Jenna  Course Neuro Lecturer Ullman Date 8/26/21 Lecture 45 Page 3 of 8 Clinical Context (CNS) – Dr. Ullman briefly introduces some clinical context to wrap up the CNS portion of the lecture. -Alzheimer’s Disease (AD) – progressive late onset dementia. Extra info – Alzheimer’s affects ~6.2 million adults in 2021, but is projected to affect 12.7 million in 20501. -Glioblastoma (GBM) – malignant tumors that forms from astrocytes (glial cells supporting neurons). Extra info – only 5% of GBM patients survive more than five years2. -Multiple Sclerosis (MS) – degeneration/breakdown of myelin in the CNS. ^apologies for the grim statistics, but for me anyways it helps add some perspective of why we’re learning this stuff, and how much learning and work still needs to be done in neuroscience/neurology/neurosurgery (and other fields!) 1. https://www.alz.org/alzheimers-dementia/facts- figures#:~:text=By%202050%2C%20the%20number%20of,slow%20or%20cure%20Alzheimer's%20disease 2. https://www.thebraintumourcharity.org/brain-tumour-diagnosis-treatment/types-of-brain-tumour-adult/glioblastoma/glioblastoma- prognosis/ Moving on from the CNS (brain and spinal cord), the Peripheral Nervous System (PNS) is a bit more anatomically ambiguous, but remember the PNS is composed of cranial and spinal nerves. Overall, as Dr. Ullman summarizes - the PNS “connects the CNS to senses, muscles, and internal organs.” PNS spinal cranial nerves As we’ll get into, the PNS is divided into several different sub-systems and divisions and it is important and HY to understand the different sub-systems and functional divisions of the PNS. That said… Q. What are the two main “sub-systems” of the PNS? A. Autonomic Nervous System & Somatic Nervous System Q. We’ve all heard of the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS). Are these divisions of the CNS or PNS? A. You guessed it – the PNS! Let’s get a bit more detailed here. -The SNS and PSNS are divisions of the Autonomic Nervous System, which from the previous question we know is a sub-system of the Peripheral Nervous System (PNS). -Broadly, the autonomic nervous system is the part of our nervous system that controls involuntary functions performed by internal organs and glands. Q. The somatic nervous system, which – like the autonomic nervous system – is a division of the PNS, functions to communicate with sense organs (i.e. taste, hearing, temperature, touch) as well as muscles to perform voluntary actions. What are the two divisions of the somatic nervous system? A. Afferent (sensory) and efferent (motor) are the two divisions of the somatic nervous system, which again is part of the PNS. Somatic afferent (sensory) – afferent sensory nerves bring INCOMING sensory information from the periphery (PNS) to the spinal cord (CNS). Somatic efferent (motor) – think EXIT – motor information exits the spinal cord (CNS) and is carried by efferent motor nerves to the periphery (PNS) involuntary an soman the afferent sensory symphitpamsymp.am effect moto  Course Neuro Lecturer Ullman Date 8/26/21 Lecture 45 Page 4 of 8 The below chart is a helpful reference for all the above questions regarding nervous system divisions. It’s tricky at first to get all these down at first, but it’s important to ensure you are properly oriented. involuntary voluntary or Hit n'figest To practice differentiating afferent from efferent (remember – both are PNS divisions!) let’s review a few scenarios: 00 Q. Stretching the skin will send sensory information to the CNS via (autonomic or somatic?) (afferent or efferent?) nerve fibers A. Somatic afferent (sensory) nerve fibers. Recall that “sense organs” (i.e. touch/stretch of the skin) communicates via somatic. Q. While walking to class through the swamp that is DC, information is being transmitted to your 0 skeletal muscle via (autonomic or somatic?) (afferent or efferent?) nerve fibers A. Somatic efferent (motor) nerve fibers. Recall that voluntary muscle function communicates via somatic. This schematic gives a picture example of the questions just discussed, and does a nice job of reinforcing the different divisions of the PNS. Dr. Ullman also notes that future lectures will dig deeper here, but getting the basic divisions down for now is a good idea.  Course Neuro Lecturer Ullman Date 8/26/21 Lecture 45 Page 5 of 8 Clinical Context (PNS): -Diabetic neuropathy – progression of diabetes can reduce blood-flow and affect nerve function. A great example of why control for diabetes (and making insulin affordable for patients!!) is so important. -Schwannoma – benign tumors that affect schwann cells. Q. What do Schwann cells do? Located in the CNS or PNS? PNS schwann my min A. Schwann cells myelinate PNS neurons. -Sciatica – pain in the sciatic nerve (longest nerve in the body) often caused by herniated discs, among other things. Next, Dr. Ullman starts to dig deeper into the cellular structures of the nervous system. He begins by introducing the anatomy of a neuron and synapse: holdsnucleus Basic neuron structure -Cell body – like all cells, neurons have a cell body! -Dendrites – dendrites increase the surface area of the cell in SA Info received body of neurons by extending projections that receive communication from other cells. -Axon – can range in size from very short to very long (i.e. sciatic nerve). -Axons are typically encased by a myelin sheath (schwann cells – PNS; oligodendrocytes – CNS) -Action potentials (AP) are electrochemical impulses that traverse axons until they reach the … -Axon Terminal – the axon terminal receives the action potential, and typically transfers the electrical signal to a chemical one by releasing neurotransmitters (i.e. acetylcholine, GABA, glutamate, etc) into the … -Synapse – neurotransmitter molecules traverse across the synapse to then bind receptor molecules (i.e. on another neuron or target organ). To further understand how neurons work together let’s turn to guest lecturer Steven Colbert … Q. Steven Colbert - How does the brain work in five words or less? A. Steven Pinker - Brain cells fire in patterns (Colbert Report, 2007)  Course Neuro Lecturer Ullman Date 8/26/21 Lecture 45 Page 6 of 8 Comedy aside – this answer is insightful – remember that we learned earlier that functions of the brain are not as simple as “x region does y function.” Networks of structures work together to create function. Many of these circuits and networks are still being discovered! With basic neuron cellular components described, let’s explore different classifications of neurons: Structural Classifications I in the.ie f -Multipolar – most neurons are multipolar in humans and other vertebrates! Multipolar neurons neurite kite have multiple projections (dendrites) extending from the cell body → transmit information to cell body → single axon → axon terminal → synapse -Bipolar neurons – have two projections to opposite poles - one dendrite and one axon -Pseudo-unipolar – begin as bipolar neurons but then fuse as a single process (“neurite”) off of the cell body -Unipolar – also have a single “neurite” extending from the cell body, with branches of dendrites and axon terminals. *Note – the above is a bit difficult to explain/conceptualize via text and static imagery. I recommend reviewing Dr. Ullman’s visual annotations (~32:00 of lecture) to understand structural differences. Directional Classifications – we’ve described afferent (sensory) and efferent (motor) neurons several times to this point, but always remember: -Afferent neurons – bring IN sensory information dorsally from PNS to spinal cord (CNS) -Efferent neurons – carries motor information as it EXITS ventrally from the spinal cord to the periphery. -Dr. Ullman also introduced us to interneurons – which connect sensory and motor information in the spinal cord (CNS). aren't or Functional Classifications – nation in spinal -Excitatory – increase the probability that target neurons fire. Recall cord the introduction to the synapse earlier – one neuron fires → releases neurotransmitter → next neuron fires. Q. What is a common excitatory neurotransmitter? A. Glutamate Glutamate excitatory -Inhibitory – as you can guess, inhibitory neurons would decrease the probability of target neurons firing. Think – it’s important to have a good balance of excitatory and inhibitory neurons for proper function. Q. What is a common inhibitory neurotransmitter? GABA inhibit  Course Neuro Lecturer Ullman Date 8/26/21 Lecture 45 Page 7 of 8 A. GABA -Modulatory – can modify the probability that a neuron target fires. For example, the substantia nigra (part of the midbrain) has dopaminergic neurons that modulate other parts of the basal ganglia (subcortical region) which pathologically can affect motor control in Parkinson’s disease. The interplay between excitatory, inhibitory, and modulatory neurons again are a wonderful representation of how neural networks communicate with each other to control function. But, the nervous system is not just neurons of course! In the final few slides, Dr. Ullman introduces us to glial cells as well as other cell types that make up the fascinating world of the nervous system. gilal cells no electrical conduction Glial cell types – it is important to note that glial cells do not produce electrical impulses, rather they support neurons via other functions detailed below. -Astrocytes – astrocytes are even more numerous than neurons, and support via multiple functions: guiding neural migration, help form the blood-brain barrier, and help maintain brain homeostasis. In CNS addition to glioblastoma, astrocytomas can arise from astrocytes in the brain and spinal cord. -Microglia – immune defense cells of the brain and spinal cord, similar to macrophages. Q. Astrocytes and microglia are located in the CNS or PNS? A. CNS! (Brain & spinal cord!) -Oligodendrocytes (CNS) & Schwann cells (PNS) -Again, we’ve introduced these already but to reinforce their function – Oligodendrocytes myelinate CNS axons vs. Schwann cells myelinate PNS axons. -Beyond the CNS vs. PNS distinction, you can see in the image on the right that oligodendrocytes have projections that myelinate portions of multiple neurons whereas schwann cells myelinate parts of just one neuron. -Digging deeper into myelination, understand that the axon is not completely, continuously myelinated, rather the myelin is deposited in segments with nodes of ranvier between them. Action potentials then “leap” from node to node via saltatory conduction.  Schwan olig white myelinated Course Neuro Lecturer Ullman hray everything else Date 8/26/21 Lecture 45 Page 8 of 8 Dr. Ullman next provides a brief introduction to gray and white matter. No need to make this more confusing than it is – White matter is composed of myelinated axons, schwann cells, and oligodendrocytes. -Vs.- Other neuronal components (cell bodies, dendrites, synapses, astrocytes, microglia, etc) make up gray matter. Dr. Ullman closes off the lecture with a wonderful summary slide. There is no new information here, but I recommend listening in (begins at 43:50 of lecture) if you want some extra *repetition!* Note: The quality of MNTS notes depends on your feedback. We encourage you to rate this noteset on a scale from 1 to 10, with 10 being the most helpful and 1 being the least. Please use the following link: https://docs.google.com/forms/d/e/1FAIpQLSeNjjQIoVdFBvZipZJA4_ik8lCbM6_r2pNVOZwv561gB Bb68w/viewform?usp=sf_link to anonymously rate the writers. In addition, please include any errors or other reasons that substantiate your rating in the Comments section. Email [email protected] with other concerns. Thank you!  Course : SFI Lecturer : Maguire-Zeiss The Medical Note-Taking Service Date : 9/8/21 Lecture Number: 64 Class of 2025 Page 1 of 7 NOTICE &DISCLAIMER Note-Taker: Taylor Martin The Medical Note-Taking Service makes every effort to provide accurate class notes. However, errors will occur from time to time. The user Corrected by: uncorrected assumes the risk for any and all errors. We recommend that you use these notes as a supplement to your own notes. Approved for distribution: yes Hi everyone! I hope you’re all enjoying the nice weather and are getting excited that, dare I say it, you’re almost done with Block 1 material! This note set will cover Synaptic Cellular Biology with Dr. Maguire- Zeiss, which was very straightforward. This note set will be organized by objective. Questions, comments, concerns, and fall cooking or baking recipes to [email protected]. Let’s get to it! 1. Know and understand the structure and function of a chemical synapse There are two types of synapses in the body, electrical and chemical, today we will focus on the latter. A chemical synapse is a functional unit and is the site of unidirectional chemical transmission via neurotransmitters between a presynaptic neuron and a postsynaptic target cell, which could be another neuron, a muscle cell (neuromuscular junction), a glial cell, an intestinal cell (Enteric Nervous System), or a macrophage. Regardless of what type of postsynaptic cell the neuron is communicating with, the synapses all have the same basic structure: 1. Presynaptic neuron has synaptic vesicles that contain neurotransmitters. 2. These neurotransmitters are secreted at the active zone of the presynaptic neuron (usually at the axon terminal aka the synaptic bouton) into the synaptic cleft (20- 40nm). 3. The neurotransmitters travel across the synaptic cleft and bind to specialized receptors on the postsynaptic cell. 4. The neurotransmitters elicit a response in the post- synaptic cell. If there is something wrong with the receptors, there may be a weakened or absent response. 5. The neurotransmitter’s action will be terminated somehow. Is the synaptic cleft part of the pre and postsynaptic cells? NO!! It is the space BETWEEN the two cells and is not a part of either of them. However, the pre and post-synaptic cells are held together by transmembrane proteins so they stay close together. 2. Name the molecular and cellular events that must occur for the release of neurotransmitters at the synapse There are two types of neurotransmitters, small molecule and peptide, we will focus on the former this time! What continues to work even after it’s fired? A neuron.  Course Lecturer Date Lecture Page 2 of 7 What are the requirements for something to be a neurotransmitter? Be synthesized in the neuron Be released in response to presynaptic depolarization Have a Ca2+ dependent release mechanism Have specific receptors on the postsynaptic cell that bind it Have specific mechanisms exist which terminate its actions For neurotransmitters to be released we need a few things to happen. 1. Action potentials depolarize presynaptic membrane 2. Voltage-gated Ca2+ channels on presynaptic membrane open in response to membrane depolarization 3. An increase in intracellular Ca2+ (~1000-fold) 4. Ca triggers vesicle FUSION with the presynaptic membrane 5. Neurotransmitters are exocytosed into the synaptic cleft Wait, so is the whole vesicle exocytosed into the synaptic cleft? NO!! It is important to know that the whole vesicle is not exocytosed out of the neuron, it fuses with the neuronal membrane and becomes part of the cell membrane for a short time. Only the neurotransmitter is released into the synaptic cleft. Let’s talk a little more about calcium-mediated vesicle fusion. Inside the presynaptic cell there are large protein complexes called SNAREs which hold the synaptic vesicles at the active zone. Once it floods into the cell, Ca2+ binds to Ca2+ sensor SNARE proteins on the vesicle, specifically synaptotagmin. This causes a conformational change of the SNARE which creates a pore in both the vesicle membrane and the presynaptic neuron membrane and neurotransmitters will be released into the synaptic cleft. What would happen if we inhibited SNAREs? Since SNAREs are required for neurotransmitter release, inhibiting them is one way we can stop neurotransmitter release. Tetanus and botulinum toxin (botox!) inhibit SNARE function to affect muscle function. So, remember how the vesicle membrane FUSED with the presynaptic neuron membrane? Now that the neurotransmitter has been released into the synaptic cleft, the vesicles need to be recycled so we can repeat this process over and over and over again. This is accomplished via endocytosis and occurs at the SIDE of the active zone (as more vesicles fuse at the active zone they push the previously fused vesicles farther to the side!). **Dr. Maguire-Zeiss mentioned that one way this is done is by using a clathrin coat. If you want more details on this refer to last year’s MNTS, but since she didn’t cover it this year, I wouldn’t focus on it.  Course Lecturer Date Lecture Page 3 of 7 The basic process of neurotransmitter production and release all starts in the cell body 1. Enzymes and proteins needed for neurotransmitter biosynthesis are made in the rough ER. 2. These proteins are sent to the Golgi for packaging. 3. Once packaged, they are transported down the axon to the presynaptic terminal via anterograde transport. 4. Once they get to the presynaptic terminal where the precursor molecules for neurotransmitters are pumped in, they can get to work synthesizing neurotransmitters in the CYTOPLASM of the bouton. Are all neurotransmitters synthesized in the cytoplasm of the presynaptic neuron? Yes, except NE, which is made inside the vesicle (more on that below!). Once synthesized in the presynaptic terminal, the neurotransmitters are packaged into vesicles and can be released once triggered by Ca2+. After neurotransmitters have bound to their postsynaptic receptors and done their job, we want to get rid of them and terminate whatever downstream effects they are causing. 3. Name and understand the biochemical events for the production, release, recycling/degradation of acetylcholine (Ach), epinephrine (E), norepinephrine (NE), and serotonin (5-HT). a. Name the rate limiting factors that control the production of these neurotransmitters and know why they are rate limiting. b. Compare and contrast how neurotransmission is terminated at cholinergic vs adrenergic synapses. Now let’s go through some specific neurotransmitters. Acetylcholine (ACh) Acetyl CoA + Choline Þ ACh ChAT Precursors: Acetyl CoA, Choline Enzyme: ChAT Rate-limiting: Choline availability Vesicular Transporter: VAChT Removal/degradation: ACh is hydrolyzed by AChE (tethered to postsynaptic side) into acetate and choline. This is one of the fastest reactions in your body! Choline is then taken back up into the presynaptic cell to make more ACh! Clinical relevance: AChE is the target of nerve gases, insecticides, and drugs. When AChE is inhibited, ACh will remain and accumulate in the synaptic cleft and cause very bad things like hyperstimulation of Ach receptors, which can lead to death. Physostigmine is a reversible AChE inhibitor used to treat glaucoma!  Course Lecturer Date Lecture Page 4 of 7 Catecholamines: NE, E (dopamine (DA) is also produced along the way) Norepinephrine (NE) 1. Tyrosine Þ L-DOPA Þ dopamine cytoplasm TH DOPA decarboxylase 2. Dopamine Þ NE DBH synapticvesicle **this reaction occurs in the synaptic vesicle Location: Part 1 occurs in the cytoplasm, Part 2 occurs in the synaptic vesicle. Precursor: Tyrosine Enzymes: tyrosine hydroxylase (TH), DOPA decarboxylase, DA-beta-hydroxylase (DBH, which is inside the vesicle) Rate limiting: TH amount and activity Tyrosine L Dopa Intermediates: L-DOPA, dopamine Vesicular Transporter: VMAT Removal/degradation: NE is taken back up into the presynaptic neuron by a NE transporter. It is then metabolized by MAO or reloaded into vesicles. If it makes its way to the periphery then the liver will take it up and metabolize it via MAO and COMT. Epinephrine (E) Wait, so how do we get E?? Remember that NE is the only neurotransmitter made inside vesicles so to get E, NE must leak out of the vesicle it was so nicely made from dopamine in. Once NE is in the cytoplasm, PNMT will convert it into E. Then, it will get loaded into a vesicle again and released into the synaptic cleft. NE Þ E PNMT Location: Cytoplasm Precursor: NE Enzyme: PNMT Rate limiting: TH amount and activity (from above) Vesicular Transporter: VMAT Removal/degradation: Same as NE.  Course Lecturer Date Lecture Page 5 of 7 Serotonin (5-HT) Tryptophan Þ 5-HTP Þ 5-HT Tryptophan-5-hydroxylase AADC Location: Cytoplasm Precursor: Tryptophan Enzymes: tryptophan-5-hydroxylase, aromatic L-amino acid decarboxylase (AADC) Intermediate: 5-hydroxytryptophan (5-HTP) Rate-limiting: Conversion of tryptophan to 5-HTP by tryptophan-5-hydroxylase Vesicular Transporter: VMAT Removal/degradation: Serotonin is taken back up into the presynaptic neuron by SERT and then metabolized by MAO or reloaded into vesicles. If it makes its way to the periphery then the liver will take it up and metabolize it via MAO. You probably noticed above that catecholamines and serotonin have some commonalities in their synthesis and transport. We can use these to affect levels of both catecholamines and serotonin. 1. They both use decarboxylases in their synthesis. 2. VMAT transports both catecholamines and serotonin into vesicles. 3. They are both metabolized by MAO. NE E How can we increase levels of catecholamines and serotonin in the synaptic cleft? Inhibit MAO. reuptake How can we decrease levels of catecholamines and serotonin? We can either inhibit decarboxylases, which they both use in their synthesis, or we can inhibit VMAT to prevent their transport into vesicles to be exocytosed. 4. Know the different classes of postsynaptic receptors and how they signal and are different from each other. Remember that neurotransmitter receptors are located on the postsynaptic membrane, and they bind neurotransmitters with high specificity. This area is sometimes called the postsynaptic density because there’s a ton of proteins there (scaffolding proteins and receptors) that look dense on an electron micrograph. There are two types of receptors: ionotropic and metabotropic. Shoutout to Emily who made this table for last years’ MNTS.  Course Lecturer Date Lecture Page 6 of 7 Here is the chart for which receptors each neurotransmitter can bind to. I recommend familiarizing yourself with this now since we will be seeing this a TON in the near future. Remember that epinephrine and norepinephrine are also known as adrenaline and noradrenaline, respectively. This is why their receptors are adrenergic and why receptors for acetylcholine are cholinergic. Remember that a neurotransmitter can bind more than one type of receptor, as long as the receptor is specific for it! Here is a fun introduction to what we will become all too familiar with next block(: Let’s go over what’s happening with each neuron. 1. In the CNS, lower motor neurons synapse directly on the muscle cell they are affecting. They are cholinergic and the receptors on the muscle are nicotinic. 2. This short sympathetic presynaptic neuron is cholinergic and synapses at the sympathetic chain ganglia. The postsynaptic receptors are nicotinic. The long postsynaptic neuron is adrenergic (NE) and the effected tissue has either alpha- or beta-adrenergic receptors. 3. This short sympathetic presynaptic neuron is cholinergic and travels through the sympathetic chain but does not synapse there. It synapses at another location. The postsynaptic neuronal receptors are nicotinic. The long postsynaptic neuron is adrenergic (NE) and the effected tissue has either alpha- or beta-adrenergic receptors. 4. This short sympathetic presynaptic neuron is cholinergic and does not synapse at the sympathetic chain but travels all the way to the adrenal medulla. The receptors on the adrenal medulla are  Course Lecturer Date Lecture Page 7 of 7 nicotinic. The adrenal medulla acts like a postsynaptic neuron and releases E and NE into the blood stream to travel to alpha- or beta-adrenergic receptors throughout the body. 5. This long parasympathetic presynaptic neuron is cholinergic and travels all the way to the wall of the organ it is affecting (intramural synapse). The postsynaptic receptors are nicotinic receptors. The short postsynaptic neuron is also cholinergic and releases ACh onto muscarinic receptors. Lastly, it was mentioned that serotonin influences peripheral tissues, not just the brain! 80% of serotonin is made in the gut, and serotonin affects many different parts of your body including the liver, adipose cells, bones, and microbes inside you! And that’s it, folks. Here is the final image that was shown in the lecture, which nicely ties everything we talked about together. See ya next time! Note: The quality of MNTS notes depends on your feedback. We encourage you to rate this noteset on a scale from 1 to 10, with 10 being the most helpful and 1 being the least. Please use the following link: https://docs.google.com/forms/d/e/1FAIpQLSeNjjQIoVdFBvZipZJA4_ik8lCbM6_r2pNVOZwv561gB Bb68w/viewform?usp=sf_link to anonymously rate the writers. In addition, please include any errors or other reasons that substantiate your rating in the Comments section. Email [email protected] with other concerns. Thank you!  Course : Neuro The Medical Note-Taking Service Lecturer : Rebeck Date : 9/1/2021 Lecture Number: 2 Class of 2025 Page 1 of 8 NOTICE &DISCLAIMER Note-Taker: Sara Ibrahim The Medical Note -Taking Service m akes every effort to provide accurate class notes. However, errors will occur from tim e to tim e. The user Corrected by: uncorrected assum es the risk for any and all errors. W e recommend that you use these n o te s a s a sup p le me n t to yo u r o wn no te s. Approved for distribution: yes Hi everyone! A lot of these concepts from the Peripheral Nervous System will come up over and over again in future anatomy and physiology modules, so I hope these notes help you build a strong foundation. Call me, beep me, if you wanna reach me → si278 ☺ Development of the PNS (Obj 1) PNIET.az mresIsEtoam The PNS develops from the neural crest while the CNS develops from the neural tube. o Neural crest cells migrate to form PNS neurons (cranial nerves, sensory neurons, autonomic neurons) and peripheral glia (Schwann cells, satellite cells). o The neural tube develops some polarity during development: the dorsal part is associated with sensory information and the ventral part is associated with motor information. ▪ Sensory neurons develop on dorsal aspect of the neural tube to form the dorsal root ganglia (DRG) along the spinal cord as shown in the diagram below. The DRG is a collection of nerve cell bodies that helps relay sensory information to the dorsal horn of the spinal cord. Sensory neurons can either go up the spinal cord to relay information to the brain, or they can synapse within the spinal cord with motor neurons (e.g. reflex arcs). Motor neuron cell bodies are found within the ventral horn of the spinal cord. They send axons out of the CNS which will then join the sensory neurons to make up the spinal nerve. The brainstem develops such that sensory neurons are located more laterally while motor neurons are located more medially. o Since this is at the level of the brain and not the spinal cord, we have the cranial nerves located next to the brainstem instead of the DRG. Types of Peripheral Nerves (Obj 2) Sensory neurons (aka afferent neurons) carry sensory information from periphery towards spinal cord and ultimately up to brain Satellite cells: located around cell bodies o Provide general support and create proper environment for peripheral neurons o Protect neurons after damage o Contribute to chronic inflammation and pain Schwann cells: provide myelination o Can remyelinate axons after damage Motor neurons aka efferent neurons o Information from CNS sent to periphery (eg. muscles)  Course Neuro Lecturer Rebeck Date 9/1/2021 Lecture 2 Page 2 of 8 Size and Myelination of Peripheral Nerves (Obj 2) Impulses travel faster in larger, more myelinated nerve fibers. o Aα-motor neurons are the largest and most heavily myelinated neurons, so they are also the fastest. o Aβ-sensory neurons are also large and myelinated, so they bring sensory information in virtually instantaneously. Pain sensation is slower because it is carried through small, unmyelinated C fibers. o If you accidentally hit your finger with a hammer, you are aware it hit your finger for a fraction of a second before you know that it hurts because the information from the sensation comes faster than the information about the pain. Autonomic nerves convey visceral motor information slowly via small, unmyelinated C fibers as well. This information doesn’t have to be sent to the brain instantaneously. Tl;dr: In terms of speed, myelinated neurons > larger neurons > smaller, unmyelinated neurons. Peripheral Nerve Coverings (Obj 5) Peripheral nerve coverings are made up of collagen, support cells, and blood vessels. They serve as protection. The endoneurium fills the space around individual axons deepest outside Schwann cells (endo = inside) o The diagram to the right shows one myelinated axon in on surrounded by the endoneurium multipleaxon s The perineurium surrounds axons or fascicles (peri = around) o The single axon surrounded by the endoneurium is grouped with other sensory and motor axons within the ve perineurium. The epineurium is the outermost layer of dense tissue around peripheral nerves that merges with adipose tissues (epi = upon) nerve Blood vessels are found within these protective coverings. Peripheral Nerve Groupings (Obj 5) Fascicles are bundles and bundles of axons. There is a lot of flexibility with the composition of fascicles. o An axon doesn’t just go to directly to one place—they have lots of collaterals, so information can go down an axon and then spread out to multiple targets. o Some areas require more protection than others e.g. areas with bones or a lot of movement. Around joints, fascicles are thinner, more numerous, and they have a thicker perineurium to protect against pressure and stretching. ▪ The PNS is more vulnerable than CNS, which has skull and vertebra for protection. A plexus is an intricate network of fibers that combine sensory and motor information i.e. a whole bunch of nerves coming together. o We will have the great pleasure of learning the specifics of the brachial and lumbosacral plexuses later in anatomy. These spinal plexuses consist of nerves coming off one part of the spinal cord that merge with nerves coming off another part of the spinal cord.  Course Neuro Lecturer Rebeck Date 9/1/2021 Lecture 2 Page 3 of 8 Organization of the Nervous System The nervous system is divided into the CNS and PNS. The PNS can be further divided into the autonomic and somatic nervous systems. Within the autonomic nervous system, we have the sympathetic, parasympathetic, and enteric nervous systems. Somatic Nervous System Broadly speaking, sensory information (e.g. touch, pain, temperature, proprioception) comes from the periphery and passes through the DRG to enter the dorsal horn of the spinal cord. o From here, sensory neurons can travel up the spinal cord or synapse with another neuron within the spinal cord. Voluntary motor information is sent from cell bodies in the ventral horn of the spinal cord. Motor neurons then meet up with the sensory axons in the peripheral nerve. While we’re talking about sensory information… let’s talk about dermatomes, cranial nerves, and referred pain. Each spinal nerve corresponds to a part of our skin that it receives sensory information from. The skin supplied by a specific spinal nerve is called a dermatome. o Dermatomes are clinically relevant. For example, if you observe a rash along a particular dermatome, it may indicate pathology of the corresponding spinal nerve (e.g. shingles). o On a related note, myotomes are muscles served by single spinal nerves. ▪ For testing of myotomes, look for weakness of particular muscles. Results may indicate a lesion to the nerve, or the nerve root at the spinal cord (e.g., pressure from the disks between vertebrae).  Course Neuro Lecturer Rebeck Date 9/1/2021 Lecture 2 Page 4 of 8 You may notice that in the dermatome diagram, there are no dermatomes for the face. This is because sensory information (vision, smell, taste, etc.) from the head and neck is picked up by cranial nerves. They also carry motor output (moving your eyes, chewing, salivation, etc.) to the head and neck. o CN X (vagus nerve) is a special outlier; it goes everywhere—the heart, lungs, GI tract, etc. Referred pain is pain perceived at a location that is not the site of injury/stimulus i.e. visceral pain from an organ is perceived by the brain as somatic pain. (Obj 6) o There is not a whole lot of sensory information for visceral organs like the heart. There is an overlap in visceral nociceptive and somatic afferent nerve terminals, so the dorsal horn and brainstem neurons can misidentify pain as more common somatic pain signals. o This is why someone with a heart attack may feel pain radiating down their left arm; the brain thinks, “I don’t usually feel my heart, so maybe something is wrong with my arm.” Autonomic Nervous System: Sympathetic vs. Parasympathetic (Obj 3) The autonomic nervous system regulates involuntary physiologic processes. It is divided into sympathetic (fight or flight) and parasympathetic (rest and digest) nervous systems. These dichotomous systems work at all times to balance each other. Let’s take an extreme example: if you’re trying to run away from a bear, your sympathetic nervous system kicks in. Your pupils dilate so you can see more, your heart rate accelerates to get more oxygen and nutrients to your muscles to run away, your bronchi dilate to bring more oxygen into the lungs, your liver stimulates glucose release to provide energy for your muscles. o At the same time, you inhibit salivation and digestion, and you relax your bladder because now is not the time to have an accident on yourself. If you’re sitting on your couch snacking on some hummus and crackers like I am currently, you don’t need to use energy to increase your heart rate, you don’t need to breathe hard, and your muscles don’t need all that energy to run away from a bear, so you can focus on digesting and such with your parasympathetic nervous system. The thing that isn’t quite explained by the examples above is the case of the genitals. Luckily, there is a helpful mnemonic to help us out: point and shoot. The parasympathetic system stimulates erections while the sympathetic nervous system stimulates orgasms.  Course Neuro Lecturer Rebeck Date 9/1/2021 Lecture 2 Page 5 of 8 Sympathetic Nerves and Ganglia o Sympathetic nerves are spinal nerves that connect to the sympathetic trunk (aka sympathetic chain ganglia aka paravertebral ganglia). ▪ The sympathetic trunk is a chain of ganglia that runs vertically along both sides of the vertebrae. It is connected to each spinal segment. o Generally, pre-ganglionic sympathetic neurons synapses in the sympathetic chain ganglia (SCG) with a post-ganglionic neuron. ▪ Sometimes, pre-ganglionic neurons don’t synapse at the SCG and just pass through until they reach prevertebral/collateral ganglia (eg. celiac, superior mesenteric, and inferior mesenteric ganglia). This is the route sympathetic nerves take to the abdomen and pelvis. o Pre-ganglionic sympathetic neurons come out of the thoracolumbar segments of the spinal cord, but they can exit the SCG at any level. ▪ Think of the SCG as an elevator—nerves can travel up or down, working in concert to spread their influence to many tissues. This allows our heart rate to increase AND breathing to increase AND eyes to dilate AND inhibit our GI tract at the same time. Parasympathetic Nerves and Ganglia o Parasympathetic nerves are mostly cranial nerves: CN III, VII, IX, but most importantly CN X (vagus nerve). Also, pelvic nerves relay parasympathetic signals to the pelvis. o Parasympathetic ganglia are called intramural ganglia because they lie near or within the walls of target organs. Somatic vs. Autonomic Nervous Systems (Obj 4) Let’s talk through two diagrams for a nice summary: Somatic Somatic neurons are single, myelinated neurons that release ACh on skeletal muscles. Sympathetic Short, lightly myelinated pre-ganglionic sympathetic neurons synapses in the sympathetic chain ganglia where it releases ACh on a long, unmyelinated post-ganglionic neuron, which releases NE on target tissues OR Lightly myelinated, pre-ganglionic sympathetic neurons bypass the SCG and synapse at a collateral ganglion and releases ACh on an unmyelinated post-ganglionic neuron OR Lightly myelinated, preganglionic sympathetic neuron bypasses the SCG and releases ACh, which stimulates the adrenal medulla to release NE and Epi. Parasympathetic Long, lightly myelinated pre-ganglionic parasympathetic axons synapse with short, unmyelinated post-ganglionic neurons at intramural ganglia. Both pre-ganglionic and post-ganglionic parasympathetic neurons release ACh.  Course Neuro Lecturer Rebeck Date 9/1/2021 Lecture 2 Page 6 of 8 Somatic Nervous System (left) - Sensory information comes in to the dorsal horn. - Motor information goes out from the ventral horn to skeletal muscle. - Sensory and motor fibers meet in the neurons and they branch in complex ways. - The route of sensory information from the viscera to the CNS overlaps with the sensory information from the periphery (since both travel through the DRG and enter the spinal cord at the dorsal horn) and this is one of the ways we may get referred pain. Sympathetic Nervous System (right) -Autonomic fibers exit from the lateral horn of the spinal cord. CNS Input into the Autonomic Nervous System (Obj 7) The autonomic nervous system is not under direct control of the CNS. The hypothalamus is the main integration center for the CNS. It gets information from the periphery, integrates it, and sends the appropriate information to nuclei in the brainstem and spinal cord. o For example, the hypothalamus can take info from amygdala, which is involved in fear and emotion, and send information to the autonomic nervous system to activate certain responses (e.g., increase heart rate when you are scared). o It can also affect cranial nerves such as the vagus nerve. Dr. Rebeck included the following clinical case to further illustrate this point: Due to a recent skiing accident, a 33 year old woman became paraplegic, losing control and sensation from the lower part of her body, but maintaining control of her arms and her breathing. Several months after her accident, she came to the emergency department with a pounding headache, heavy sweating, and a low heart rate. She demonstrated high blood pressure (even though individuals with spinal cord injuries are typically hypotensive). o This is a case of autonomic dysreflexia, where there is a sudden onset of very high blood pressure. It is common in patients with spinal cord injuries above T6. o There are usually reflexes within spinal cord of the autonomic nervous system to regulate blood pressure. In this case, there is a loss of brainstem control on these reflexes, so small stimuli (such as pressure on the bladder or wearing tight clothes) can cause sudden, dramatic increases in blood pressure. The hypothalamus is no longer able to communicate all the way down to the spinal cord to inhibit this stress response.  somatic ventral dorsal sympathetic Lateral him Course Neuro Lecturer Rebeck pantymp mgrs here Date 9/1/2021 Lecture 2 Page 7 of 8 Enteric Nervous System (Obj 8) The enteric nervous system is a part of the autonomic nervous system found in the lining of the GI tract all the way from the esophagus to the anus. There are thousands of small ganglia within the GI tract between the layers of GI muscle, which affect the muscles, epithelia, arterioles, and secretory cells. ANS Motor: control of motility; regulation of gastric secretions, pancreatic enzymes, and bile; regulation of fluid exchange and blood flow o In the GI mucosa, cell secretions help with digestion. o Parasympathetic information (from vagus and pelvic nerves) promotes digestion and peristalsis while sympathetic information turns the system off. ANS Sensory: detection of distension and GI contents o There are receptors in the GI mucosa to monitor the tract; for example, a blockage would stimulate mechanoreceptors to indicate that there is a problem. This sensory information is then relayed to the CNS. Local autonomous motor function: enteric reflexes (e.g., motility, secretions) can function in absence of other ANS input o There are layers of muscle surrounding the mucosa which are innervated by neurons that tell those muscles to contract and relax to help move food through the tract (peristalsis). CNS Involvement in the ENS (Obj 7) Parasympathetic information can be sent to the GI tract through the vagus and pelvic neurons and sympathetic information can be sent through lateral horn of spinal cord. The sight or smell of food (detected by the CNS) can promote salivation and other secretions. Sensory information from the GI tract including pain and discomfort can be sent up to the CNS. Enteric glia between the layers of GI muscle play a role in chronic inflammation and pain. Dr. Rebeck ended the lecture with some clinical correlates to illustrate the relevance of the ENS: o ENS-immune interactions are involved in Crohn’s disease and inflammatory bowel disease. o Neurons projecting to GI tract can be important for CNS diseases. ▪ For example, prions (infectious, misfolded proteins) can travel from these neurons to the spinal cord and brain ▪ Inflammation in the periphery can contribute to early stages of neurodegeneration (e.g., Parkinson’s disease) o The ENS relies on neurotransmitters found throughout the CNS and PNS (e.g., ACh, NE), so drugs that target neuronal transmission in the brain can have GI side effects.