Lecture Objectives PDF

Objectives **Lecture 1: Organization of the Nervous System** 1. Describe the physiological and anatomical divisions of the nervous system. - The central nervous system (CNS) is housed in bony protective cavities: the cranium and the vertebral canal. - The peripheral nervous system (...

Objectives **Lecture 1: Organization of the Nervous System** 1. Describe the physiological and anatomical divisions of the nervous system. - The central nervous system (CNS) is housed in bony protective cavities: the cranium and the vertebral canal. - The peripheral nervous system (PNS) connects the CNS to peripheral "targets" such as muscle (smooth, skeletal, and cardiac) and glands, as well as to sensory endings. - Despite the chaotic appearance of the swirling lines that depict the nervous system, it is highly organized. Deciphering the structural and functional organization will be the job of neuroanatomy. - **The CNS consists of white matter and gray matter. The cerebral cortex is gray mater.** - **The gray matter has the neurons and cell bodies. The white matter has the axons.** - **Cranial nerves function through different afferent and efferent fibers.** 2. Describe the bony encasement of the CNS - The brain is encased in the cranium by these bones: - Frontal - Parietal - Occipital - Temporal - Sphenoid - The [vertebral canal] is formed from the vertebral foramina when these are stacked into a vertebral column. - 3. Identify the major divisions of the spinal cord - The three meningeal layers wrapping the spinal cord are the same as those that wrap the brain: - Dura - Arachnoid - Pia - Spinal dura is [not] attached to bone. (Cranial dura is attached to bone.) - The space between vertebral bone and the underlying spinal dura is the "epidural" space. - The spinal cord ends at approximately segment L2. - Lumbar and sacral nerve roots extend from L2 to their respective exit point. The bundle of roots is the "cauda equina" --horse tail. - A lumbar puncture can be used to: collect CSF from the subarachnoid space, introduce spinal anesthesia, introduce epidural anesthesia - **Afferent fibers bring signals to the CNS. Efferent fibers carry the response from the CNS.** - **Joint, skin, and skeletal muscle bring messages to the CNS via somatosensory fibers. Viscera and vessels bring messages to the CNS via viscerosensory fibers. Skeletal muscle receive a response from the CNS via somatomotor fibers. Glands, smooth muscle and cardiac muscle receive messages from the CNS via visceromotor fibers.** - **Visceral- gut, heart, smooth muscles and cardiac muscles, organs** - **Somatic is skeletal muscle** 4. Describe the venous drainage of the brain - Four named divisions of internal carotid artery: - cervical - petrous -- petrous portion of temporal bone - Cavernous -- cavernous sinus - cerebral - The [internal jugular vein] provides the main route of venous drainage from the brain. - There are numerous smaller accessory drainage pathways.. - The internal jugular vein provides the main route of venous drainage from the brain. - There are numerous smaller accessory drainage pathways. Though a vertebral vein runs along with the vertebral artery in the transverse foraminae, the vein provides only an accessory route of drainage for the brain. - Other accessory routes of venous drainage include emissary veins, superior ophthalmic vein, and pterygoid plexus. - 5. Identify the describe the meninges - **The brain and spinal cord are covered by three membranes:** - **The innermost layer is [pia mater]** - **The middle is [arachnoid mater] (membrane)** - **\* between the arachnoid mater and pia mater is the subarachnoid space (filled with CSF)** - **The outermost layer is [dura mater]** - **The pia mater is a thin layer of connective tissue cells. Very closely applied to the surface of the brain and covers blood vessels. The glia limitans adjoins the pia from the brain side and is separated from the pia by a basement membrane. Pia adheres associated glia limitans very tightly; this combined structure called the pial-glial membrane** - **The cells of the arachnoid membrane are linked together by *tight junctions.* The arachnoid isolates the CSF in the subarachnoid space from blood in the overlying vessels of the Dura mater** - **The dura mater is a thick, inelastic membrane that forms an outer protective envelope around the brain. The dura has two layers that split to form the intracranial venous sinuses** - **Subarachnoid space- in-between arachnoid and pia mater- arteries carrying blood travel through here** - [Emissary veins] connect intracranial vessels with veins in the scalp. Infections of the scalp can pass into the cranium by way of emissary veins. This is the basis of the "danger zone" of the scalp. - The brain "floats" in the CSF. CSF also accumulates in the subarachnoid space surrounding the spinal cord. - 6. Describe and Identify the major divisions of the brain - The cerebrum is divided into four cerebral lobes: - Frontal - Parietal - Temporal - Occipital - The brain includes the: - Telencephalon - Diencephalon - Mesencephalon (midbrain) - Metencephalon (Pons and Cerebellum) - Myelencephalon (Medulla oblongata) - 7. Identify the ventricles of the brain - CSF is produced within the brain from structures called choroid plexus located in brain ventricles. - Left and right lateral ventricles each have three horns: anterior (frontal), posterior (occipital), and inferior (temporal). - Third ventricle is in the midline; it is connected to the lateral ventricles through the interventricular foramen (of Monro) - The fourth ventricle is also midline; it is connected to the third ventricle by way of the cerebral aqueduct and to the central canal of the spinal cord. - CSF exits the ventricles by way of the lateral appertures (of Luschka) and by a midline aperture (of Magendie) - 8. Describe the Blood Brain Barrier - The blood-brain barrier is a product primarily of tight junctions between endothelial cells lining brain capillaries. - The barrier prevents hydrophilic molecules from moving freely between the lumen of the blood vessel and brain tissue. - Molecules in the blood that are required by neurons must be selectively transported across the blood-brain barrier. - The blood-CSF barrier is present in the choroid plexus. - The cell junctions between choroid plexus epithelial cells prevent the free flow of fluid from the brain to the CSF. CSF must be transported across this cell barrier. - The same barrier also prevents substances from diffusing from the CSF to the brain parenchyma. - **Lecture 2: Physiology of Neurons** 1. Describe the difference between a myelinated and unmyelinated sheaths of an axon - **Myelinated axons in the central nervous system** - **A single oligodendrocyte emits several processes, each of which winds in a spiral fashion around an axon to form the myelin sheath. Oligodendrocytes can myelinate more than one axon.** - **Myelinated axon in the peripheral nervous system-** - **A Schwann cell forms a myelinated sheath for peripheral axons in much the same fashion as oligodendrocytes do for central ones, except that each Schwann cell myelinates a single axon.** - **Myelinated moves faster than unmyelinated axon. Signals have to be propagated via sodium channels. With myelinated nodes of Rainer allow you to jump the signal so it moves faster** - **Axons are still viable even if the myelin goes away.** 2. Describe the morphology of a neuron - **Projects from the cell body at the site of the axonal hillock (or initial segment)** - **Carries impulse [away] from the cell body** - **May be myelinated or not myelinated** - **Contains numerous Na^+^ channels** - 3. Describe Axonal Degeneration and Regeneration - **Step 1: Degeneration of synaptic terminal distal to lesion- the synaptic terminals, distal to the lesion in the axon degenerate.** - **Step 2: Wallerian degeneration- loss of axonal structure distal to lesion** - **Step 3: Myelin degeneration- myelin degenerates leaving debris behind** - **Step 4: Scavenging of debris- microglia (CNS) and macrophages (PNS) scavenge the debris of breakdown.** - **Step 5: Chromatolysis- ER degenerates** - **Step 6: Retrograde transneuronal degeneration- the retrograde neuron's terminals retract and the neuron degenerates** - **Step 7: Anterograde transneuronal degeneration- the anterograde neuron degenerates** - **The rate of regeneration is limited by the rate of slow axonal transport to about 1 mm/day.** - **The thicker and shorter the dendrite, the more likely is a dendritic EPSP to trigger an action potential at the axon hillock** 4. Describe the types of axonal transport and the materials transported in each type - **The neuronal cytoskeleton is important for transport, maintaining shape/structure, and compartmentalizing the cell. The cytoskeleton is made of microtubules, neurofilaments and microfilaments.** - **Kinesin does anterograde movement and Dynein does retrograde movement. They carried by microtubules.** - **Anterograde movement is forward and retrograde movement is backwards** - **Fast anterograde is 400 mm/day. It is done by Kinesin and the material transported are mitochondria and vesicles.** - **Fast retrograde is 200 to 300 mm/day. It is done by dynein and the material is degraded vesicular membrane and absorbed exogenous material.** - **Slow anterograde is 1 to 5 mm/day. The mechanism is unknown and the material transported is cytoskeletal elements, soluble proteins and actin.** 5. Describe what happens at the presynaptic terminal of a neuron in the resting state and activated state - **Axons of different types are bound together with loose connective tissue called endoneurium. These are in turn bound together into a fascicle by a connective tissue sheath called perineurium. The perineurium provides structural stability to the nerve** - **However, strength is increased even more by a third connective tissue layer called the epineurium. Within a single nerve, the axons may shift from one fascicle to another as the nerve traverses the body. The intertwining of the axons results in intertwining of the fascicles which adds further strength to the nerve** - 6. Identify the basic properties of axonal potentials - **Excitatory input to a neuron usually generates a flow of positive charge across the dendritic membrane. Because the interior of a resting neuron is polarized negatively, this inward current *[depolarizes]* (makes the membrane voltage more positive) the cell** - **Action potentials can vary and look different depending on location and they function with different times. stimulus creates action potential, the cell depolarizes (become more positive), repolarization phase- downward slope (returns to resting potential), hyperpolarization is a dip** - **Electronic potentials are proportional to the stimulus** - **An action potential occurs if the membrane potential reaches the threshold** - **Sodium and Potassium are important. Sodium conductance increases first into the cell. Then potassium conductance happens on the interior of the cell and leaves the cell.** - **The change in membrane potential (Vm) caused by a neurotransmitter at the postsynaptic membrane is called *postsynaptic potential* (PSP).** - **If the neurotransmitter is excitatory, it produces a *depolarizing* Excitatory PSP (EPSP).** - **If the neurotransmitter is inhibitory, it produces a *hyperpolarizing* Inhibitory PSP (IPSP).** - Excitatory PostSynaptic Potentials - **Postsynaptic increase in sodium or calcium conductance, Na - most prevalent - leads to depolarization just as for action potential** - **Postsynaptic decrease in potassium conductance, Both increase the positive charge in the cell = *EXCITATORY*** - **Inhibitory PostSynaptic Potentials** - **Increased potassium efflux or chloride influx, ** - **Both decrease the positive charge in the cell = more negative = *INHIBITORY* ** - **Spatial summation is the adding together of EPSPs or IPSPs over [SPACE]** - **Temporal summation is the adding together of EPSPs and IPSPs over [TIME]** - **Lecture 3: Membrane Potentials and Action Potentials** 1. Describe an action potential - **As the number of Na+ ions increases, the accumulation of positive charges internally become greater than externally. Therefore, the membrane is said to be depolarized at about 40mV** - **An action potential is a rapid, all-or-none change in the membrane potential followed by a return to the resting membrane potential. Voltage-dependent ion channels in the plasma membrane are the basis for action potentials.** - **An action potential is propagated with the same shape and size along the entire length of an axon.** - **Action potentials are usually initiated at the initial segment of the axon.** - **The action potential is the basis of the signal-carrying ability of nerve cells.** - **The patterns of conducted action potentials encode the information conveyed by nerve cells.** - **When the membrane is in thermodynamic equilibrium (i.e. no net flux of ions), the membrane potential must be equal to the Nernst potential. However, in physiology, due to active ion pumps, the inside and outside of a cell are not in equilibrium. In this case the resting potential can be determined from the Goldman equation.** - **The Goldman Equation is very similar to the Nerst Equation but it predicts the membrane potential based upon the concentration of several types of ions and the membrane's permeability to each of those ions** - **Axons are specialized for rapid, reliable, and efficient transmission of electrical signals. Myelinated axons are specialized for reliably and rapidly carrying electrical signals from one place to other places, in the form of action potentials. An action potential starts at the initial segment \>\> due to high density of voltage-gated Na+ channels.** - **All-or-none principle:** - **A neuron fires with the same potency each time** - **Frequency for firing can vary** - **It either fires or not; it cannot partially fire** - **Reliable ** - **-Voltage threshold for triggering ** - **-Once triggered, it is self-shaping** - **Can travel very long distances ** - **-Self-propagating ** - **-Passive spread of electrical signal \~1mm** - **Rapid ** - **-Propagate up to 120 m/s** - **Specific ** - **-Carries a signal from one point to another** - **Threshold is important. Needs to be above threshold to fire. Action potentials have large density of sodium to make the action potential to happen. In the nodes of Rainer the sodium channels are more concentrated.** - 2. Identify the changes during the action potential. - **What happens if a membrane is initially permeable to K+ and then temporarily switches to becoming most permeable to Na+? It will depolarize** - **resting membrane is more permeable to K^+^ than Na^+^ due to K^+^ leaky channels** - **Na^+^-K^+^ pump (ion transporter) maintaining concentration gradient** - **Membrane is impermeable to negatively charged proteins (A^-^)** - 3. Identify what the propagation of an action potential - **Action potential propagation requires both active and passive current flow. When the actional potential starts upstream the sodium channels are first activated which causes the action potential to begin. As the action potential moves forward the channels will close and causing the axon to be refractory so it does not move backwards. The sodium channels upstream will close and the potassium channels will open so that axon will be begin to repolarize. Sodium channels will continue to open as the action potential moves down the axon downstream.** - **The Propagation of the Action Potential= the advancement of an action potential in a single direction along the length of the membrane** - **Some movement of sodium is passive after the sodium channels have already opened and the action potential has happened** 4. Describe the difference between the conduction velocities of myelinated and unmyelinated axons - **Conduction Velocities of Myelinated And Unmyelinated Axons as Functions of Axon Diameter- Bigger diameter of myelin has faster velocity** - **Unmyelinated Axons= propagation of the action potential is dependent on the sequential activation of successive Na+ ion channels** - **Myelinated Axons=voltage gated Na+ ion channels farther apart and mainly clustered near the Nodes of Ranvier. Current jumps from node to node making the process become much faster. Clusters of sodium channels help it move faster so that you do not have to create a new one, it skips from node to node** - **the larger the difference between the membrane potential and the equilibrium potential for a given ion, the larger the imbalance between electrical and concentration gradients and the larger the net movement of the ion** - 5. Describe the resting membrane potential - **Resting potential is the voltage difference between the cytoplasmic and extracellular side of the plasmalemma.** - **Neurons have constant permeability K+ channels that formulate a charge difference across the cell** - **The cytoplasmic part will be negative** - **The intracellular concentration of K+ is greater than the extracellular concentration** - **Some K+ ions flow down a concentration gradient via K+ Leaky channels** - **Lecture 4: Synaptic Transmission at the Neuromuscular Junction and CNS** 1. Overview; presynaptic mechanisms and postsynaptic mechanisms - The major difference between the neuromuscular junction and neuronal synapses is ***the type of neurotransmitter used*** \>\>All skeletal neuromuscular junctions use acetylcholine (Ach) - The contact site determines the way in which the synapse is named: **axodendritic**, **axosomatic**, **axoaxonic** 2. Describe dendritic spines - In the CNS, in more than 90% of all excitatory synapses, the postsynaptic site is a **dendritic spine**. - The spines contain : transmitter receptors, structural proteins, and proteins for endocytosis and glycolysis. - These spines increase the opportunity for a dendrite to form synapses, and also isolate (electrically or chemically) individual synapses from the rest of the cell. 3. Describe ascending reticular systems - Several systems of neurons regulate the general excitability of the CNS. Each of these **modulatory systems** use a different neurotransmitter - A small set of neurons (several thousand) forms the center of the system. Neurons of the disperse systems arise from the central core of the brain. Neurons interact via their axons spreading across the brain. - Ascending reticular systems- consciousness is dependent on this system. It is located in the midbrain and rostral pons. It sends a signal to the thalamic intralaminar nuclei, hypothalamus, and basal forebrain. The Neurotransmitter is unknown but it may be glutamate. It is involved in alertness. 4. Describe some neural systems where dopamine is found - Cholinergic Projection Systems use acetylcholine as main neurotransmitter. In the basal forebrain it is located in the nucleus basalis, medial septal nucleus of diagonal band where the signal is transported to the cerebral cortex. In the pontomesenecphalic region it is located in the pedunculopontine nucleus and laterodorsal tegmental nucleus where the signal is transported to the thalamus, cerebellum, pons, and medulla. It uses muscarinic receptors. Involved in alertness and memory. - Dopaminergic Projection Systems use dopamine as the main neutrotransmitter. The system is located in the midbrain at the substantia nigra, pars compacta and ventral tegmental area and transmit the signal to the striatum, limbic cotex, amygdala, nucleus accumbens, prefrontal cortex. It is involved in movements, initiative and working memory. - The cells of the ventral tegmental area innverate the prefrontal cortex of the forebrain and parts of the limbic system. These are the regions that mediate reinforcement or reward, and involved in psychiatric disorders like Parkinsons. - Dopamine is found in a number of neural systems - [Nigrostriatal] system projects from the substantia nigra to the caudate nucleus and putamen - [Mesolimbic] system projects from ventral tegmental area to the limbic system (including the nucleus accumbens, amygdala, and hippocampus) - [Mesocortical] system projects from the ventral tegmental area to the cortex - Dopamine receptors are metabotropic. Two families of dopamine receptors: - D1-like receptors are postsynaptic, whereas D2-like receptors are pre- and postsynaptic - Noradrenergic Projection Systems use norepinephrine as a main neurotransmitter. It is located in the pons at the locus ceruleus and lateral tegmental area. It transmits signals to the entire CNS. It is involved in alertness and mood elevation. The locus coeruleus cells believed to be involved in the regulation of attention, arousal, and sleep-wake cycles, also in learning and memory, anxiety, pain, mood, and brain metabolism. - The serotonergic projection systems use serotonin as the main neurotransmitter. It is locatd in the midbrain, pons and raphe nuclei. It transmits signals to the entire CNS. It is involved in mood elevation. The raphe nuclei cells believed to be involved in the control of sleep wake cycles and also the different stages of sleep. Serotonergic raphe neurons have also been associated with the control of mood and certain emotional behavior. - Histaminic Projection systems use histamine as the main neurotransmitter. It is located in the hypothalamus at the tuberomammillary nucleus and the midbrain at the reticular formation. It sends messages to the entire brain and is involved in alertness. 5. Describe the neurotransmitters of the brain - Neural synapses are represented by their input to the *pyramidal neuron* of the cerebral cortex - **1) Excitatory synapses**: Fast excitatory synapses in the brain use **glutamate** or **aspartate**: *glutamatergic synapses.* These amino acids bind to a group of fast, ligand-gated cation channels \>\> generate an **excitatory postsynaptic potential** (EPSP). This EPSP is similar but much smaller than the EPSP in muscle produced by acetylcholine - **2) Inhibitory synapses**: The inhibitory transmitters **GABA** and **glycine** bind to receptors that gate Cl^-^ -selective channels - **3) Modulatory synapses**: [neuromodulator + membrane receptor + G-protein] \>\> intracellular signal cascade. The systems do not bind directly but help support Neurotransmitters. 6. Describe ISPS and ESPS - EPSPs in the Brain Are Mediated by Glutamate-Gated Channels - Glutamate can act on four major classes of receptors, one is a G-protein coupled or metabotropic receptor, and the others are ion channels or ionotropic receptors. Metabotropic receptors have seven membrane-spanning segments and are linked to heterotrimeric G proteins - Ionotropic glutamate receptors are: - AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid), - NMDA (N-methyl-D-aspartate), - Kainate - Ionotropic receptors Permeable to: - AMPA \-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--Na^+^, K^+^, (Ca2^+^ rarely) \>\> fast excitation - NMDA \-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-- Na^+^, K^+^, Ca2^+^ - Kainate \-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-- Na^+^, K^+^ - Depending on the voltage potential the channels may not open. When the membrane is more negative at -80 mV the AMPA channel opens but the NMDA channels does not open. Mg2+ blocks the NMDA receptor. When the membrane is more positive at -40 mV both the AMPA and NMDA channels will open. Mg2+ will not block the NMDA channel and Ca2+ is able to flow into the cell. - NMDA receptors are coincidence detectors; that is, in order for Ca2+ to enter through NMDA receptor channels, two conditions must be met simultaneously at the postsynaptic membrane. These conditions are: - glutamate binding to the NMDA receptor and anion flux through AMPA receptor channels - glutamate binding to the NMDA receptor and depolarization of the cell membrane - glutamate binding to the NMDA receptor and removal of the Mg2+ block from the NMDA receptor. - depolarization of the cell membrane and inactivation of AMPA receptors - IPSPs in the Brain Are Mediated by the GABA~A~ receptor - **GABA** and **glycine** are the two major synaptic inhibitors in the CNS. Both the GABA~A~ and the glycine receptors are ionotropic receptors (Cl^-^ selective). The GABA~B~ receptor is a G-protein coupled metabotropic receptor (linked to either the opening of K^+^ or suppression of Ca^2+^ channels). - Because of the need for control of inhibition, the GABA~A~ receptor has other binding sites for different chemicals. The probable natural modulators of GABA~A~ receptor are the metabolites of progesterone, corticosterone, and testosterone - Benzodiazepines (i.e., diazepam --Valium-) and barbiturates (i.e., Phenobarbital) can also bind to these specific binding sites on the GABA~A~ receptor channel. Benzodiazepines increase the frequency, and barbiturates increase the duration of channel opening. Benzodiazepines can also increase the Cl^-^ conductance of the GABA~A~ receptor. - People take these medications for anxiety **Lecture 5: The Autonomic Nervous System** 1. Describe the anatomical organization of the sympathetic and parasympathetic systems including preganglionic and postganglionic neurons and synapses. - The autonomic nervous system is responsible for maintaining the internal environment of the body (homeostasis). Within the autonomic nervous system, two neurons are required to reach a target organ, *pre*ganglionic neuron and a *post*ganglionic neuron. - The preganglionic neuron originates in the central nervous system \>\> it forms synapse with the postganglionic neuron, the cell body of which is located in ganglia. - The autonomic nervous system is divided into the *sympathetic* and *parasympathetic* systems. 2. Explain the functional organization of the sympathetic and parasympathetic systems. - The **sympathetic system** is catabolic (burns energy). The sympathetic nervous system is also called the **thoracolumbar** system because the ganglia are located lateral to the vertebral column in the thoracic and lumber regions (T1-L3). Because the ganglia are fixed along the back, the postganglionic sympathetic fibers can be quite long. Within the sympathetic system the preganglionic axons form synapses with many postganglionic cells, therefore giving this system a widespread action - Sympathetic pathway: - Cell bodies of presynaptic neurons are located in gray matter (the intermediolateral cell column) of spinal cord segments C8 -- L2. - Axons exit the spinal cord by way of the [ventral root]. The ventral root combines with a dorsal root to form a spinal nerve. - Presynaptic sympathetic fibers leave the spinal nerve and pass through the white [ramus communicans]. The white ramus communicans connects with the [sympathetic chain]. - What happens to fibers that synapse in a sympathetic ganglion? - The postganglionic cell fiber, or axon, travels along a gray ramus communicans to connect with a spinal nerve. The axon may follow either the dorsal or ventral primary ramus to be distributed to the body wall and limbs (but not to viscera in the body cavities). - These axons continue to target organs: smooth muscle in blood vessels, sweat glands, erector pili muscles. - The **parasympathetic system** is anabolic (tries to conserve energy). The cell bodies of preganglionic parasympathetic neurons are located in specific nuclei of the medulla, pons, midbrain, and in the S2 through S4 level of the spinal cord. - brain \>\> with four cranial nerves: the oculomotor nerve (CN III), the facial nerve (CN VII), the glossopharyngeal nerve (CN IX), and the vagus nerve (CN X). - CN III, VII, and IX originate in three groups of nuclei: - (1): the **Edinger-Westphal nucleus** \>\> subnucleus of the oculomotor complex in the mesencephalon. Parasympathetic neurons in this nucleus project to the eye via CN III and synapse onto postganglionic neurons in the ciliary ganglion - (2): the **Superior salivatory nucleus** \>\> in the rostral medulla. Parasympathetic neurons in this nucleus project to the pterygopalatine via CN VII \>\> supply the lacrimal glands. Another branch of the facial nerve carries preganglionic fibers to the submandibular ganglion \>\> supply submandibular and sublingual glands - (3): the **Inferior salivatory nucleus**, and the rostral part of the **nucleus ambiguus** in the rostral medulla contain parasympathetic neurons that project via CN IX to the otic ganglion \>\> supply to the parotid gland - Cranial Nerve X: Cell bodies are found in the medulla within the **nucleus ambiguus** and the dorsal motor nucleus of the vagus \>\> supplies parasympathetic innervation to all the viscera of the thorax and abdomen, including the GI tract between the pharynx and distal end of the colon. - - S2 --S4 \>\> the pelvic splanchnic nerves. - The parasympathetic system: **craniosacral** 3. Define the sympathetic chain - The sympathetic chain extends from the neck to the pelvis and lies along the lateral border of the vertebral bodies. It is connected to ventral rami by communicating rami (white and gray). - 4. Identify the differences between the parasympathetic vs. sympathetic responses - In response to fear, exercise, or other types of stress, the sympathetic division produces a massive and coordinated output to all end organs simultaneously (fight-or-flight), whereas parasympathetic output ceases - This sympathetic response includes increases in heart rate, cardiac contractility, blood pressure, and ventilation of the lungs; bronchial dilatation, sweating, piloerection, release of glucose into the blood, and decreased GI activity - Parasympathetic- rest and digest a. Slow heartbeat, decreased force of contraction, decrease blood pressure, miosis (pupil constriction), bronchoconstriction, stimulates digestion, vasodilation. - Sympathetic Nervous System- fight or flight b. Accelerates heartbeat, increase force of contraction, increase blood pressure, mydriasis (pupil dilation), bronchodilation, inhibits digestion, vasoconstriction **Lecture 6: Autonomic Nervous System(Part 2)** 1. Describe Acetylcholine Synthesis and Degradation - Acetylcholine is synthesized from acetyl coenzyme A (acetyl Co A) and choline. - Acetylcholine action is terminated by acetylcholinesterase. - Acetylcholine is synthesized in the presynaptic terminal from Acetyl CoA and Choline by Choline acetyltransferase - This enzyme choline acetyltransferase is the rate-limiting enzyme for the formation of Acetylcholine - The enzyme Acetylcholinesterase is located in the synaptic cleft and is responsible for the break-down of Acetylcholine back into Acetate and Choline - 2. Describe what neurotransmitters are - Cells of the nervous system communicate with one another by electrical signals or releasing small molecules known as neurotransmitters. These neurotransmitters bind to ion channels and G-protein-coupled receptors - There are three major catecholamines: Dopamine, norepinephrine, and epinephrine. All of these catecholamine come from tyrosine. Tyrosine hydroxylase contributes in to tyrosine to dihydroxyphenlalanine (L-dopa). Dopamine is derived from the decarboxylation of L-dopa - Norepinephrine is derived from the hydroxylation of dopamine - The rate-limiting step in the synthesis of NE and E is the conversion of tyrosine to DOPA by tyrosine hydroxylase. - The degradative enzymes COMT (catechol-o-methyl-transferase) and MAO (monoamine oxidase) are mainly involved in the inactivation of norepinephrine 3. Describe the location of the various types of receptors ie alpha and beta receptors - α1 receptors: - vascular smooth muscle, on GI and bladder sphincters, and radial muscle of the eye - cause excitation (contraction) - vasoconstriction - Gq IP3 - α2 receptors - presynaptic nerve terminals, platelets, fat cells, walls of GI tract - cause inhibition (dilatation) - inhibition of adenylate cyclase and decrease in cAMP - β1 receptors - SA node, AV node, ventricular muscle of heart - produce excitation (increases heart rate, contractility, - increased conduction velocity - stimulation of adenylate cyclase and increase in cAMP - β2 receptors - vascular smooth muscle of skeletal muscle, bronchioles, walls of GI tract and bladder - produce relaxation (dilation of vascular smooth muscle and bronchioles, relaxation of bladder wall) - stimulation of adenylate cyclase and increase in cAMP 4. Describe afferent feedback and what it involves - The hypothalamus is the most important brain region for coordinating autonomic output. - The hypothalamus projects to the parabrachial nucleus, medullary raphe, NTS (nucleus tractus solitarius), central gray matter, locus coeruleus, dorsal motor nucleus of the vagus, nucleus ambiguous, and intermediolateral cell column of the spinal cord. - The hypothalamus plays a dominant role in the integration of higher cortical and limbic systems with autonomic control. - feeding, thermoregulation, circadian rhythms, water balance, emotions, sexual drive, reproduction, motivation - Afferent feedback to the [brainstem] by way of visceral afferents will stimulate or inhibit, as appropriate, autonomic neurons that regulate blood pressure, respiratory rate (and blood gas concentrations), and other autonomic functions. The afferent input signals regulate the stimulatory level of fibers that end on visceral efferent motor neurons in the thoracic spinal cord. - Internal organs are densely innervated by visceral afferents. These receptors monitors either nociceptive (painful) input or sensitive to mechanical and chemical stimuli (stretch of the heart, blood vessels, and hollow viscera, and changes in PCO~2~, PO~2~, pH, blood glucose, temperature of skin and internal organs) - Most of the visceral nociceptive fibers travel with sympathetic nerves, while axons from physiological receptors travel with parasympathetic fibers. - The visceral afferent axons are mainly concentrated in the vagus nerve, which carries non-nociceptive afferent input from the viscera of thorax and abdomen to the CNS. The cell bodies of vagal afferents are located in the nodose ganglion of medulla. - In the CNS, the visceral pain input is mapped \'viscerotopically\' at the level of the spinal cord because most visceral nociceptive fibers travel with the sympathetic fibers and enter the spinal cord along with a spinal nerve. This mapping is also present in the brain stem, but not at the level of cerebral cortex. Awareness of visceral pain is not localized to a specific organ but is instead *referred* to the dermatome that is innervated by the same spinal nerve. - Afferent fibers travel through both sympathetic and parasympathetic nerves. The sensory cell body is contained in a ganglion. One neuron (not two) connects the visceral organ with the CNS. - Afferent fibers traveling in autonomic nerves may converge upon sensory neurons in the spinal cord that also synapse with somatic afferents. The convergence "confuses" the brain, which "feels" pain in the region supplied by the somatic nerve, even though it is the autonomic fiber that has been activated by pain. Since the visceral afferent fiber travels with the sympathetic ganglion from the dermatome you can have referred pain because the brain is not sure where the initial pain signal came from since they traveled together. Think about what visceral organ can cause the referred pain - The myenteric plexus lies between the external longitudinal and the deeper circular smooth-muscle layers. It is involved in the control of motility - Submucosal (Meissner's) plexus lies between the circular muscle and the most internal layer of smooth muscle, the muscularis mucosae. It is involved in the control of ion and fluid transport **Lecture 7: Neuronal Microenvironment** 1. Describe what the neuronal microenvironment - Neuronal microenvironment includes the extracellular fluid (ECF), capillaries, glial cells, and adjacent neurons. The concentration of solutes in *brain ECF* (BECF) fluctuate with neural activity. Similarly, changes in BECF can influence nerve cell behavior - Blood-brain-barrier (BBB) protects BECF from fluctuations in blood composition - The cerebrospinal fluid (CSF) strongly influences the BECF composition. The surrounding glial cells "condition" the BECF 2. Describe the formation and reabsorption of cerebral spinal fluid (CSF). - CSF is a colorless, watery liquid which fills the ventricles of the brain and forms a thin layer around the outside of the brain and spinal cord in the subarachnoid space - CSF is secreted by a highly vascularized epithelial structure, ***choroid plexus.*** The composition of CSF is highly regulated - The **ventricles** of the brain are four small compartments. Each contains a *choroid plexus* and is filled with CSF. The two lateral ventricles are the largest and each communicate with the third ventricle via the two interventricular **foramina of Monro.** The third ventricle communicates with the fourth ventricle by the **cerebral aqueduct of Sylvius** - The fourth ventricle is continuous with the central canal of the spinal cord. CSF escapes from the fourth ventricle and flows into the subarachnoid space via three foramina. Two laterally (left and right) placed **foramina of Luschka.** Midline opening in the roof of the fourth ventricle, **foramen of Magendie**. All of these three foramina in the 4^th^ ventricle will drain the CSF into the subarachnoid space which will then circulate throughout the brain - The Arachnoid Granulations function to absorb the CSF. Transport some of the CSF made by the choroid plexus into the vascular system on a daily basis - Most of the arachnoid granulations protrude into lacunae lateralis,diverticula of the superior sagittal sinus. The center of the arachnoid granulation is known as the arachnoid trabecula is continuous into the subarachnoid space - Most of the CSF is produced by the **choroid plexuses** which are located in ventricles. Capillaries also form a small amount of CSF - CSF production is 500 ml/day \>\>\> [CSF volume of 150 ml] is replaced three times a day - CSF percolates throughout the subarachnoid space, then absorbed into venous blood from the superior sagittal sinus - Choroid epithelial cells are bound to one another by tight junctions, which makes the epithelium an effective barrier to free diffusion. Ion concentration of CSF is rigidly maintained. Micronutrients are selectively transported - CSF forms in 2 steps: - Ultrafiltration of plasma across the capillary wall into the ECF (underneath the basolateral membrane of the choroid epithelium) - Choroid epithelium cells secrete fluid into the ventricle - CSF production occurs with a net transfer of NaCl which drives water isosmotically - CSF is analyzed clinically for diagnosis 3. Describe Normal pressure hydrocephalus - In Normal pressure hydrocephalus Spinal tap reveals normal pressure readings, but MRI of the head will show enlargement of all four ventricles. An infection or inflammation of the meninges damages arachnoid villi, and causes impaired CSF absorption - Patients typically have progressive dementia, urinary incontinence, and gait disturbance - CSF shunt to venous blood or to the peritoneal cavity helps reducing CSF pressure 4. Describe the components of cerebral edema - Cerebral Edema will cause increased intracranial pressure and is sometimes referred to as brain swelling. There is a net accumulation of water - Cell swelling in the absence of net water accumulation in the brain does *not* constitute cerebral edema. For ex; intense neural activity causes a rapid shift of fluid from the BECF to the intracellular space, with no net charge in brain water content. If the cerebral edema is *generalized*, it can be tolerated until intracerebral pressure exceeds arterial blood pressure - Sensors in the medulla detect the increased intracerebral pressure and can partially compensate by increasing arterial pressure **Lecture 8: Clinical Case Correlations: Multiple Sclerosis and Demyelinating Diseases** 1. Identify the signs and symptoms of multiple sclerosis - Multiple Sclerosis is the most common demyelinating disease of the central nervous system. An autoimmune disease directed against the myelin or oligodendrocytes. Oligodendrocyte In the CNS can myelinate multiple axons. Schwan cells in PNS can myelinate one axon. Unclear trigger, more common in women than one axon. Particularly found within the younger age group population. - With Multiple sclerosis the CNS carries lesions located within the periventricular white matter, corpus collosum, optic nerves, and the dorsal spinal cord. The white matter of the spinal cord carries axons. Multiple sclerosis affects any are that is composed of myelin and oligodendrocyte loss. - Signs and symptoms of Multiple Sclerosis include Sensory disturbances, weakness, vision loss (optic neuritis), abnormal gait etc. Most common presentation is paresthesia which are pins and needles, burning, loss of sensation or numbness 2. Describe the disease course of multiple sclerosis - Patients with MS have remissions and relapses. - The exacerbation and relapse is due to the occurrence of active inflammation of a white matter tract in the CNS. - A remission occurs when the inflammation subsides and the demyelinated axons recover some of their function, and are able to conduct action potentials - Currently no cure for multiple sclerosis - There are currently several FDA approved drugs that can be used to treat MS - Some of those drugs include interferons, Glatiramer Acetate, and Natalizumab, Glucocorticoids 3. Identify Landry-Guillain-Barre Syndrome - Landry-Guillain Barre Syndrome involves paralysis of nerves feeding the brain stem. Patients will require mechanical ventilation. The initial stage reaches a plateau and then gradually resolves. The pathology is demyelination in the PNS. The symptoms include weakness, numbness and paralysis. - Landry-Guillain Barre Syndrome typically follows a recent viral infection. 4. Describe Acute Disseminated Encephalomyelitis and treatment for disease - Acute Disseminated Encephalomyelitis is characterized by multifocal inflammation and demyelination. It is caused by an autoimmune response that causes demyelination of the axon. It is associated with a recent rabies or smallpox vaccine and can also be associated with a recent infection such as varicella or measles. - It is clinically distinguished from MS when people have a background of a recent history of vaccination or infection. - It can cause alterations in consciousness or seizures. - MRI will show various lesions that are acute in nature. The CSF will have lymphocytic pleocytosis, protein elevation, and intrathecal synthesis of gammaglobulins - Treatment is high dose corticosteroids and immunoglobulins (IVIG) which is used for patients who do not respond to high dose corticosteroids. **Lecture 9: Clinical Case Corrélations: Neuromuscular Junction Disorders** 1. Describe the clinical presentation of Myasthenia Gravis - Myasthenia Gravis is an autoimmune disorder that affects the neuromuscular junction. The acetylcholine receptor that is located on the post-synaptic membrane is a ligand-gated ion channel composed of 5 subunits. The alpha subunit in particular is targeted, and autoantibodies are formed specifically against the alpha subunit. These autoantibodies will cause a loss of acetylcholine receptors on the post-synaptic membrane; there are several autoantibodies that target the acetylcholine receptor. - Clinically Myasthenia Gravis Presents as weakness of commonly used muscles such as Ptosis, diplopia, dysarthria, respiratory and limb weakness. The weakness is fluctuating- may increase throughout the day and improve within sustained rest 2. Describe how to diagnose and treatment of Myasthenia Gravis - Screening is done for Myasthenia Gravis through a blood test for a Acetylcholine receptor antibody. An ice pack test can be used as well. Place an ice pack over the eye demonstrating ptosis. If the ptosis improves, it is considered supportive for myasthenia gravis. - Symptomatic Treatment is done with cholinesterase inhibitors which increase the concentration of acetylcholine at the Acetylcholine receptor. Corticosteroids are the first-line immunosuppressive therapy for myasthenia gravis. 3. Identify the signs, symptoms and treatment of botulism - Botulism is caused by ingesting the neurotoxin of the bacterium Clostridium botulinum. Botulinum toxin binds irreversibly to the presynaptic nerve endings of the peripheral nerve system and cranial nerves. The toxin inhibits the ability of synaptic vesicles to dock with the presynaptic membrane of the nerve vesicles. Vesicles cannot fuse to the presynaptic membrane and release Acetylcholine into the synaptic cleft. Under the age of 1 are more susceptible after ingesting honey. - Signs and symptoms of Botulism include hypotonia in infants and descending paralysis. Descending Paralysis is a weakness that starts in the cranial nerves and descends downward towards upper extremities, respiratory muscles and finally lower extremities - Botulism is diagnosed through blood and stool. Food samples can test for toxin. - Treatment for Botulism is supportive care. Patients are monitored for respiratory decompensation. There is no cure. Analgesics can help. 4. Describe Tick Paralysis - Tick paralysis is a rare disease that usually affects children. The disease is associated with approximately 43 different types of tic species. Some cases are known to be within the Rocky Mountains, Pacific northwest, and areas with trees and shrubs. **Lecture 10: Clinical Case Corrélations: Normal Pressure Hydrocephalus and Meningitis** 1. **Identify the signs and symptoms of normal pressure hydrocephalus** - **Normal Pressure Hydrocephalus is excess fluid accumulation in the brain. It can be due to inadequate resorption where the arachnoid granulations do not absorb the CSF (most common cause). It can be due to overproduction of CSF or an obstruction which is less common.** - **Signs and symptoms of Normal Pressure Hydrocephalus include:** - **gait disorder/ trouble walking which can worsen over a period of several weeks to months** - **Increased urinary urgency and frequency** - **Dementia with forgetfulness and impairment in decision making** - **CT scans show enlarged/dilated ventricles** - **Wet, wacky, wobbly** 2. **Describe the treatment of normal pressure hydrocephalus** - **Treatment includes shunting CNS from the ventricle so it will not accumulate** - **There is usually a good prognosis when the initial presentation is a gait disturbance and mild cognitive symptoms** 3. **Describe meningitis and how it is treated** - **Meningitis is when the meninges are infected and inflamed. There are various types of meningitis.** - **Classic symptoms of meningitis include a headache and fever. People are also known to have a stiff neck also known as nuchal rigidity.** - **Diagnosis of meningitis is done by retrieving spinal fluid via a spinal tap. CSF is obtained through a lumbar puncture. A needle is inserted below L2 into the subarachnoid space. The spinal cord will not be damaged because it ends at L2. The long roots of the cauda equina will slide away from the needle tip. CSF is analyzed to determine the type of meningitis present. CSF Fluid can be cultured.** - **Treatment for bacterial meningitis is antibiotics and corticosteroids.** - **Treatment for viral meningitis is supportive treatment with analgesics, antiemetics, and intravenous hydration. There is a good prognosis if treated early.**