Test III Study Guide
Test III Study Guide NSCI 3310
Popular in Cellular Neuroscience
Joseph Merritt Ramsey
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Popular in Neuroscience
This 50 page Study Guide was uploaded by Joseph Merritt Ramsey on Friday November 6, 2015. The Study Guide belongs to NSCI 3310 at Tulane University taught by Jeffery Tasker in Fall 2015. Since its upload, it has received 110 views. For similar materials see Cellular Neuroscience in Neuroscience at Tulane University.
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Date Created: 11/06/15
October 19, 2015 Synaptic Transmission: The Postsynaptic Perspective Continued Shunting Inhibition o This is an additional type of inhibition o Consider the scenario: GABA activation opens Chloride Channel, so they are open to flow But if the cell is at -70mV, which is fairly common, no flow will occur because there is no driving force Potentials are equal But if Chloride channels are open and an excitatory potential passively diffused down the axon, some positive charge is lost because of the channels The open channels respond to the potential change: slight depolarization gives Chlorine a positive Driving Force current So some positive charge is lost This is known as Shunting o Figure A o This process is described and explained through Ohm’s Law Ohm’s law can be used to make sense of the situation Opening Chloride channels decreases the resistance of the cell Decreased resistance results in decreased Potential V = IR Synaptic Modulation Introduction to Modulation o Metabatropic Receptors Modulation involves slower acting receptors and actions They don’t form ion channels Respond through signaling cascade o Associated with G-Protein Trimer Protein G-Proteins bind a Guanosine Nucleotide (GDP and GTP) o The Receptor is a 7-Transmembrane Protein o Secondary Messengers Activates another intercellular ligand Often acts on an ion channel Often activates a kinase, which activates the target protein G-Proteins o 3 Protein Subunits α, γ, β These subunits for a membrane associated protein o Ligand Binding to the GPCR (G-Proteins Coupled Receptor) The binding to the receptor activates the G-Protein Associated to the receptor α Subunit associates with Guanosine Nucleotide Has GDP and binds GTP instead for activation Initiates the cascade for the Second Messenger o Alpha and GTP affect the Primary Effector β/γ Subunit now separated from the Alpha It can act directly on its target protein o Associated with a Transducer All the action is associated with a specific G-Protein, known as a Transducer o Figure B o GPCR Process 1. First Messenger (Neurotransmitter) Binds to receptor 2. G-Protein Activated through GTP (Protein is the Transducer) 3. Primary Effector Enzyme Activated (Membrane Associated, results in production of 2 Messenger) 4. 2 Messenger Formed (works on secondary effector) 5. Secondary Effector Activated (many times a kinase) 6. Phosphorylation of target proteins Types of Metabatropic Interactions o 1) cAMP Messenger System Overview Two Subtypes: I. β Adrenal Receptor (G Seaning Stimulatory) II. 2 Adrenal Receptor (G mIaning Inhibitory) o 2) Phosphoinostosol System Known as the G Qrotein PLC Targeted (Primary Effector) PIP2is an associated protein that forms the 2 Messenger I. DAG o Acts on PKC (Protein Kinase C) o Calcium sensitive mechanism II. IP 3 o Acts on Calcium Channels in Smooth ER, increasing intercellular Calcium Concentration o 3) Direct β/γ Action nd The α unit functions above for 2 Messenger Cascades β/γ works directly on channels and proteins Work on GIRK Channels (Potassium, K, Channels) How do they function? They create an inhibitory effect o I. Opening Potassium Channels (-80 E ) ion o II. They decrease membrane resistance They act slowly and have a lingering effect Two Examples I. Muscarinic Receptors in the Heart II. GABABreceptors in the CNS Metabotropic Receptors’ Effects on the Cell o Unique Aspects They can open OR close channels Can occur distant from the target protein Ionotropic is only local, but Metabotropic can be both A single receptor can also interact with numerous targets o Example on Potassium Channels (closing) The Two Main Effects: 1. Increase Resistance 2. Depolarize the Neuron o Physiological Consideration Neurotransmitters Paired With Receptors NEUROTRANSMITTER GPCR Glutamate mGluR 1-8 GABA GABA B Acetylcholine Muscarinic (M 1-5 Dopamine D 1-4 Norepinephrine Β (G S α2(G I Serotonin 5-HT (1, 2, 4-7) Histamine H 1-4 Endocannabinoids CB 1nd CB 2 October 21, 2015 Synaptic Modulation Overview of Modulation o Presynaptic – occurs before the action potential fires, so on the terminal, geographically after the Hillock Diffuse Spillover from the cleft (Extrasynaptic) Immediate Retrograde Messenger Axo-axonic Synapses o Postsynaptic – occurs after the signal has reached the cell, so geographically before the Hillock Axo-dendtritic, Axo-somatic Spilled over diffusion can occur here as well (but more likely in the Presynaptic Mechanisms because Postsynaptically must occur far up the axon and to soma and dendrites) This method must overcome reuptake and Glial contributions Glia can produce Gliotransmitters that affect the extrasynaptic membrane on the Soma and Dendrites, thus serving as a Post Synaptic modulation mechanism o Mechanism Effects: 1) Changes Membrane Potential because of Ion Shifting 2) Changes Membrane Resistance because of Channel Openings Postsynaptic Modulations Mechanisms o Overview We’ve studies and reviewed at Neuropeptide acting as AcH acting on Muscarinic Metabotropic proteins in the heart contrasting the AcH fast acting Ionotropic Here is a CNS view, looking at Metabotropic EPSP’s and IPSP’s o Excitatory Action 1. Peptide Example Occurring in the muscular junction 2. Glutamate Occurring in the CNS Closes K Channels through GPCR o Closes off K, causing an overall depolarizing effect o Increases membrane resistance, enhancing charge diffusion Acts mainly on voltage gated channels, but affects Leak channels as well Just as in the Peptide Muscarinic Receptor in the muscular Junction, Glutamate Metabotropic receptors cause an elongated effect in the cell o Inhibitory Action 1. GABA B GABA iB the Metabotropic Receptor It also couples with K-Channels o Unlike Glutamate Metabotropic receptors, GABA opens GIRK channels on the membrane o Opening does the opposite of Glutamate: Decreases resistance, so shunting occurs Opens flow of K, which hyperpolarizes the cell Also has an elongated effect Presynaptic Modulation Mechanisms o Overview Axo-axonic terminal and Retrograde actions both affect the output of Neurotransmitter in the synapse o Excitatory Action There isn’t one – Axo-axonic or Retrograde mGluR is always Inhibitory o Inhibitory Action 1. Glutamate Glutamate Metabotropic receptors affects synaptic proteins in the synapse region o Protein machinery on the terminal: Synatix SNAP-25 Those effects inhibit the budding and excretion of Neurotransmitter vesicles (Glutamate and GABA) 2. GABA GABA (Betabotropic) affects Calcium channels, thus decreasing Calcium presence in the Presynaptic Terminal The inhibition of Voltage Gated Calcium channels decreases Ca presence, thus inhibiting Neurotransmitter Vesicle release (GABA and Glutamate) Synaptic Recordings of Synaptic Modulation o 1. Glutamate (Done through mGluR, Metabotropic Glutamate) First measured spontaneous Excitatory Events (Glutamatergic EPSP’s) A known probability is calculated Small, quick Negative Charges Then measured the cell with mGluAgonist (so ligand that activates the Metabotropic Glutamate proteins) The resulting action probability is then observed ad calculated The mGluR activation in the CNS on an Axo-axonic synapse was found to decrease Excitatory Minis So there was a decrease in vesicular release So we know that mGluR Receptors are Inhibitory on Axo- axonic Synapses o Not directly inhibitory, but inhibitory by increasing the amount of Glutamatergic Ionotropic interactions How does this occur Biologically? 1. Glutamate spilling over in the form of negative feedback 2. Other cells in the region are excreting Glutamate, which diffuses 3. New evidence might suggest a dendritic role o 2. GABA (Done through Norepinephrine) First measured spontaneous, hyperpolarizing, Inhibitory Events (GABA BPSP’s) These are all inhibitory, even the Ionotropic (unlike the above Glutamate example) Small, quick positive charges Norepinephrine acts as an agonist for GABA B New probability recorded with higher GABA acBivation Found that Norepinephrine causes an increase in events (higher probability) of GABAAinhibition (GABA minis) So it facilitates Ionotropic GABA action October 23, 2015 Neurotransmitters Defining a Neurotransmitter o 1. Synthesized/Stored in the Presynaptic Terminal This is determined through Immunohistochemistry (marking through an antigen to determine location of molecules) o 2. Released with Stimulation Microdialysis to take up and peform chemical assay o 3. Specific Receptors Exist on the Membrane for the Transmitter Neuropharmacology Autoradiology – chemical tag placed on a transmitter to see the receptor General Overview of Neurotransmitters o Classes 1. Small Molecule (Amino Acids, AcH, Biogenics) Amino acids have Glycine, GABA, Glutamate o They can be excitatory or inhibitory o Glycine on spinal cord and retina AcH Catecholamines o The Tyrosine chain Neurotransmitters o Serotonin 2. Neuropeptides Always use GPCR Often Neurohumeral Junction o Affects endocrine system Directly into blood stream Neuro hormone Hypothalamic effects 3. Unconventional (gases, Endocannabinoids) o Immunohistochemistry Very important technique used for tracking location/movement of particles An antibody is generated for a particular compound Generated through Polyclonal Process Foreign compound is given to animal The animals produce natural antibodies which are garnered for use The antibody can then be tagged with the desired amount of additional proteins to increase specificity o Discovery of Neurotransmitters Theory had existed for years before – The Reticulate Theory Proposed by Golgi that the nervous system was just a continuous electrical connection Ramon y Cajal found through Golgi staining that gaps existed So he knew it was not continuous as Golgi suggested So inferred the Neuron Doctrine o Chemical synapses exist for communication 1921 Otto Loewi Experiment A frog heart could be used and stimulated after death and removal Focused on the Vegas Nerve o Has an autonomic effect that decreases the heart beat when activated o One heart in one chamber had the nerve, the other didn’t The two chambers were connected, so particles and chemicals could diffuse but there was no electrical connection o When the Vegas nerve in chamber I was activated, the heart in chamber II was activated soon after Determined that the nerve release a chemical, thus allowing diffusion to affect the heart o Eventually found to be AcH in heart o Important Protein Considerations 1. Cytosolic Synthesized by free ribosomes synthesize and affect 2 Types: Cytoskeleton and Enzymes Neuro Application: o Cytoskeleton transports building blocks and vesicles of Neurotransmitters o Enzymes piece them together 2. Nuclear 3. Membrane Associated 3 Types: Attached, ER, and Vesicular Neuro Application: o Neurotransmitters are contained in vesicles Class Overview o 1. Small Neurotransmitters A. Amino Acids (GABA, Glutamate, Glycine) B. Acetylcholine C. Biogenic Amines I. Catecholamines (Tyrosine Derivatives) II. Serotonin o 2. Neuropeptides o 3. Unconventional Neurotransmitters A. Gases B. Endocannabinoids Neurotransmitter Creation and Packaging (Synthesis and Packaging) o I) Small Molecule Cytosolic Proteins and precursor components combine through enzymes to form the Neurotransmitter This occurs in the Synapse The Components are sent down the axon unassembled Through slow axoplasmic transport (Diffusion through Proteins) After the enzymes put together the transmitter in the Synapse, the membrane proteins recognize the Transmitter and form the vesicles o II) Neuropeptides Precursor proteins are cleaved into multiple proteins This occurs in the Soma This cleavage process creates the Neurotransmitter The packaged vesicles are sent down the Axon Done through Fast Anterograde Transport (Through the cytoskeletal proteins) Neurotransmitter Action at the Synapse o Small Molecule High concentration on the Presynaptic region, especially close to the membrane (concentrated at membrane) Clathrin coating surrounds the newly formed Neurotransmitter molecules, Dynamin clips to create vesicle (before the Neurotransmitters are unpackaged) These vesicles are moved by vesicular transport proteins Recycling Occurs Reuptake and Packaging (taken right back in through Neurotransmitter channels on the presynaptic membrane) Uptake Into the Glial Cells (glial cells take and break down into basic components) Breakdown (occurs in both) Vesicles appear as clear, smaller dots o Neuropeptide Already packaged when arriving, have higher concentration farther towards the axon than the synaptic membrane So their release occurs farther up, as well, outside the active site o Results in Extrasynaptic Communication (Called Volume Transmission, because it increases the Extracellular Volume of Neurotransmitter) Vesicles appear as larger, black dots o Co-Release They actually don’t act completely separately, and are Colocally Stored Small Molecule – smaller, clear Neuropeptides – larger, darker Storage Pool/Readily Releasable Pool Predominantly Small Molecule (Synaptic Vesicles) Needs large action to release Neuropeptides (Synaptic Granules) So common, small activity mostly affects Small Molecule Large responses affect Neuropeptides as well (which are released off the synaptic membrane farther up) Modulation Because of the fast response of Small Molecule, they can be depleted from the terminal But Peptides are longer lasting molecules that occur father away from the synapse o This gives Neuropeptides the ability to prime a cellular region because there signal lingers Small-Molecule Neurotransmitters o 1. Amino Acids 1. Glutamate (Glycine sometimes used as excitatory in Spinal Cord and Retina) Overview o Amino acid neurotransmitters are used and recycled through terminals Synthesis o Glutamine is catalyzed and synthesized by Glutaminase Release o Ionotropic Receptors: NMDA, AMPA, Kainate o Metabotropic Receptors: mGluR1 to mGlu8 Termination of Action/Recycling o A. Astrocytes and neurons have Glutamate receptors on their membranes that take up Glutamate The molecule is then broken down and Glutamine (done by glutamine synthetase) precursor is funneled back into presynaptic terminal o B. Glutamate is also taken up by the presynaptic terminal But as this point it is merely repackaged, not broken down o C. Glutamate is also not broken down in the cleft (contrasting AcH which is broken down by the basements membrane) 2. GABA Synthesis o Glutamate is the GABA precursor (Gamma Amino- butyric Acid) o Glutamic Acid Decarboxylase and Pyridoxal Phosphate Release o Ionotropic Receptors: GABA (Al Channel) o Metabotropic Receptors: GABA (ABfects K and Ca Channels) Termination of Action/Recycling o A. Astrocytes take up but don’t break down and reship to terminal like Glutamate o B. GABA Transporters present on the axon terminal also take up GABA o 2. Acetylcholine Action Process Synthesis o Acetyl CoA + Choline worked on by Acetyl- transferase Release and Receptors o Ionotropic: Nicotinic o Metabotropic: Muscarinic Termination/Recycling (Breakdown/Uptake) o Acetylcholinesterase breaks down into its components in the basement membrane of the Neuromuscular junction o Choline is then taken up through its transporter on the terminal membrane It is then reformed inside the cell Systems: I. Cholinergic System o Diffuse System It occurs everywhere in the brain, intrinsic (localized) creation and CNS effect Interneurons are present throughout CNS o Amygdala is GABAergic (extrinsic), allowing for body coordination o Sources in the Brain 1. PMT Complex (PontoMesencephaloTegmental Complex) Basal forebrain connections 2. Medial Septum Cortical and Hippocampal projections o Involved in memory and attention o Innervates directly on Hippocampus AcH Fibers are lost early on in Alzheimer’s disease 3. Basal Nucleus of Meynart Cortical projections o Systems overview The centers are in the brain, but lead to projections all throughout the brain Discrete projections have specific target sites October 26, 2015 Neurotransmitters: Continued Small-Molecule Neurotransmitters o 1. Amino Acids o 2. Acetylcholine Systems: I. Cholinergic System II. Autonomic Nervous System o General Setup Sympathetic – fight or flight Parasympathetic – rest and digest AcH affects both They work through a Double Neuron System with Ganglion (Cluster of Cell Bodies in the PNS) Preganglionic cells – project from CNS to the ganglion Postganglionic Cells – project from ganglion to PNS target sites CNS sends information to PNS Ganglion, which sends another signal to target destination o Sympathetic Ganglion located very close to the Spinal Cord Coordinated response Pre uses AcH, Post uses Norepinephrine System Preganglionic – thoracic and lumbar segments send their extensions o Make AcH and synapse on ganglion Postganglionic – have a synapse with the preganglionic nerve o Once AcH acts on the Postganglionic nerve, it releases Norepinephrine to respond o Parasympathetic Ganglion located very close to the Final Destination Immediate localized response Pre and Post Ganglion use AcH System Preganglionic – most have origin in the Medulla Brainstem o This nerve in the Parasympathetic system is very long Postganglionic – very short, soma is in in extremely close proximity to the target area o 3. Catecholamines Types: 1. Dopamine 2. Epinephrine (More systemic) 3. Norepinephrine Creation (Linear Process beginning with Tyrosine) Tyrosine o Tyrosine Hydroxylase DOPA o DOPA Decarboxylase Dopamine o Dopamine β Hydroxylase Norepinephrine o Phenol Ethanol Epinephrine Effects Mood/Stress Attention/Coordinated Arousal Energy and Homeostasis Reward System ALL Catecholamines work through GPCR’s (Never Ionotropic) A. Dopamine – Metabotropic D1 through D4 B. Norepinephrine – α, β Epinephrine – α, β Systems A. Dopamine System o Sources I) Ventral Tegmental Area Heavily involved in the biological reward system Schizophrenia is linked to the Hyperstimulation of this region II) Substnatia Nigra Parkinson’s is linked with the degradation of this region Deals with Motor Control and Coordination o Directly linked to the striatum III) Basal Hypothalamus Neuroendocrine gland modulation Affects different endocrine and neurotransmitter presence through the Anterior Pituitary o Synapse Dopamine taken back up through the transporter channels VTA-Nucleus Accumbens Reward System Dopamine reuptake can be blocked B. Norepinephrine System (in the CNS) o Sources I) Pons The Locus Coeruleus regulates o Most important contributor Dorsal Noradrenergic Bundle – projections to cortical, cerebellar (including hypothalamus) regions as well as the spinal cord II) Medulla The Brainstem NE System Ventral Noradrenergic Bundle – to the Subcortical basal region o Overview Involved in mood and arousal SNRI’s block Norepinephrine reuptake in the cell to treat depression C. Norepinephrine System (Autonomic Nervous System) o Post ganglionic nerve are involved (not in parasympathetic, only autonomic sympathetic o Does so through Beta receptors o 4. Serotonin (5-HT) Process of synthesis begins with Tryptophan (amino acid) Tryptophan o Tyrptophan 5-Hydroxylase 5-Hydroxytryptophan o Aromatic L-amino Acid Decarboxylase Serotonin Receptors – 5-HT 1 5-HT 7 But 5-HT 4s not in the brain And 5-HT i3 Ionotropic Systems A. Serotonin System Neuropeptides o Overview All Neuropeptides use GPCR (no known Ionotropic Receptors for Neuropeptides) The PNS System in the Gut and the Hypothalamus have been studied the most for Neuropeptides Hypothalamic Cells have both Neuroendocrine and Neurotransmitter effects 1. Pituitary (Endocrine System) 2. Autonomic System Neuron Projections (Neurotransmitter, so Nervous System) o 1. Magnocellular (Posterior Pituitary) Hypothalamic signal causes the release of Neuropeptides directly into the general bloodstream Produces: 1. Oxytocin – parturition and milk ejection o Known as the “love hormone” Induces pair bonding in species o Possibly involved with facial recognition o Patruition (Child Birth) and Milk Ejection Relaxes smooth muscle cells in the uterus and mammary glands 2. Vasopressin – ADH, antidiuretic hormone (ADH) o Controls blood osmolality o Helps fluid homeostasis and hydration o 2. Parvocellular (Anterior Pituitary) Neuropeptides are released from the Hypothalamus in a system These can be inhibitory or excitatory o (GnRH, TRH, CRH, GHRH, Dopamine) Eventually lead to the secretion of pituitary hormones from the Anterior Pituitary Lobe o (Prolactin, FSH and LH, TSH, ACTH, Growth Hormone) System Breakdown: i. Parvocellular Neurosecretory Cells are Synapsed with the Hypothalamus ii. Hormones transport occurs in axons (because these are packaged neuropeptides in the somas) iii. The synapses regions communicate and hypophysiotropic hormones are released, which flow through the blood down to the Anterior Pituitary iv. These hormone stimulate or inhibit the hormone production from the Anterior Pituitary October 28, 2015 Neuroanatomy Overview o CNS – anything held within bone Brain Spinal Cord o PNS – everything else outside bone Spinal Nerves Cranial Nerves o General 1. Sensory Signal Enters the Brain 2. Brain Communicates with the Motor Component (Autonomic and Somatic) 3. Action Occurs o Sensory is Afferent (Towards, input) and Motor is Efferent (Away, output) Anatomy o Figure Outline Rostral Caudal Dorsal Ventral Posterior Superior Inferior Anterior o Planar Cuts Sagittal Horizontal Coronal o General Brain Outline Brain Stem Cerebrum Cerebellum Neural Development Overview o Neural Plate/Disk Formation Embryo made up of three layers 1. Endoderm – viscera 2. Mesoderm – bones, muscles 3. Ectoderm – skin, nervous tissue Neurulation occurs in Ectoderm o Neurulation Occurs in the first Three Weeks 1. The Normal Ectoderm has a Neural Plate 2. The embryo begins to fold and the Plate becomes the Neural Groove 3. As the Embryo continues to fold, it comes over itself and the groove becomes the Neural Tube and the Neural Crest Neural Tube and Neural Crest begin the real differentiation Crest – o Crest folds eventually branch out to become the PNS o This is the Rostral/Anterior section Tube – o Spinal Cord and brain develop o This is the Posterior/Caudal section Differentiation of the CNS o Overview Develops from Neurulation, Neural Tube (Cord, Ventricles) and Crest (Spreading) o Phase I: Primary Vesicle Formation This is the primary formation the lays the foundation for neural development Occurs at the Rostral (Front) end of the Neural Tube Forms three vesicles (Sections) 1. Prosencephalon (Forebrain) 2. Mesencephalon (Midbrain) 3. Rhombencephalon (Hindbrain) Spinal cords end also forms o Phase II: Secondary Vesicle Formation Now the vesicles begin to take shape and form as their respective brain regions Sequence: 1) Prosencephalon o Quickly becomes three entities: A. Optic Vesicles – becomes optic nerve and retina B. Diencephalon – becomes thalamus, hypothalamus C. Telencephalon – becomes cortex 2) Mesencephalon o 2 Differentiation brings about its shape and form A. Tectum – Superior and Inferior Colliculus control motor and optic coordination B. Tegmentum – dopamine reward system C. Cerebra Aqueduct – continuing and connecting the ventricles (3 in the Forebrain and 4 in the Hindbrain) 3) Rhombencephalon o Has two sections, one more Rostrally locate and one more Cadudally, and each have a slightly different appearance Rostral I. Rhombic lips swell and eventually develop into the Cerebellum II. The Pons develops with its Neural connections Caudal I. The Fourth Ventricle forms II. The Medulla takes shape as well, present with Medullary Pyramids o Some functions: A. Cerebellum Controls movement and coordination Convergence of inputs from spinal cord and cerebral cortex Coordinated movement B. Pons The “Bridge,” with 90% of descending axons from the cortex synapsing in the Pons Relays to the Cerebellum C. Medulla Somatic Sensory Relay Houses some autonomic sensory and motor nuclei 4) Spinal Cord o The spinal cord mix of Grey and White matter is of utmost importance Grey: the horns (ventral and dorsal) and the intermediate zone White: columns (dorsal, lateral, and ventral) Ascends (afferent) and descends (efferent) o The cell bodies for many CNS structures o CNS complete overview (post differentiation) Sections 1. Forebrain (Prosencephalon) o Telencephalon o Diencephalon o Optic Nerves 2. Midbrain (Mesecephalon) o Tectum o Tegmentum 3. Hindbrain (Rhombencephalon) o Cerebellum o Pons o Medulla 4. Spinal Cord 5. Ventricles Ventricles Rostral Caudal o Telencephalon Diencephalon Mesencephalon Rhombencephalon Spinal Cord o Lateral Ventrical Third Ventricle Cerebral Aqueduct Fourth Ventricle Spinal Cord Divisions and Subdivisions (up the body, so Caudal to Rostral or Posterior to Anterior) 1. Spinal Cord 2. Medulla 3. Pons 4. Cerebellum 5. Midbrain (Tectum and Tegmentum) 6. Diancephalon (Hypothalamus, Thalamus) 7. Cerebral Hemispheres (Telencephalon) October 30, 2015 Peripheral Nervous System Organization o Somatic Nervous System Skeletal, striated Voluntary control o Autonomic Nervous System Cardiac, smooth Involuntary control Broken down into Three Components 1) Sympathetic – fight or flight 2) Enteric – gut 3) Parasympathetic – rest and digest The Four Properties for Assessing Spinal Cord Construction o 4 Divisions exist I. Central (Neck) – C1-C8 II. Thoracic (Mid Back) – T1-T12 III. Lumbar (Lower Back) – L1-L5 IV. Sacral (Tailbone) – S1-S5 and Coc1 o Spinal Nerves Made up of Dorsal Roots and Ventral Roots meeting up in the Cord Dorsal Roots – sensory (afferent) Ventral Roots – motor (efferent) o Spinal Cord Once the nerves reach the cord, we have three main parts for Grey Matter: 1) Dorsal Horn o Sensory afferent nerves o The nerve ending are in the periphery 2) Ventral Horn o Motor efferent axons are present o Innervate on Striated muscle (in the body) 3) Intermediolateral Columns o Thoracic segments There are also important parts for White Matter: 1) Most of the Columns (except the one above) o Dorsal, Ventral, Lateral, and Ventro-Lateral 2) Ascending sensory, descending Motor o Once they are in the CNS, they are Grey Matter Spinal Ganglia Dorsal root ganglia house cell bodies for sensory input o All the PNS sensory nerves have their bodies here o These are Pseudounipolar Cells So their body is in the Ganglion, but their connections occur in the grey matter region where they are synapsed o Observations to Consider Second Order Neurons These are the connections to the primary sensory neurons whose bodies are in the ganglion Some eventually innervate on Medulla Many begin at the ganglion and enter the spinal cord Columns Dorsal Columns – up and afferent Ventral Columns – down and efferent Autonomic Example Preganglionic nerves in the thoracic section These cell bodies are in the intermediate lateral zone Sectional Swellings The Cervical and lumbar regions are swollen out due to the large number of nerves from the arms and legs (huge volume) Grey matte sections Autonomic Motor System (Somatic will be discussed in more depth in the discussion on systems) o Ganglionic Synapses Parasympathetic Preganglionic neuron synapses occur are present in Cranial and Sacral Regions Sympathetic Preganglionic Neurons are present throughout the Lumbar and Thoracic regions Norepinephrine released as the transmitter to the synapse Then epinephrine from the adrenal can be released as a hormone to the body Somatic vs. Autonomic Nerves Sensory Systems Broad Overview of Systems o Common Organization Sensory Receptors are Unique Transduction occurs on these receptors (physical stimuli become electrical signals) Epithelial Cells in Visual, Auditory, and Gustatory Neurons in Somatic Sensory and Olfactory o Encoding Breakdown 1. Modality – what type? 2. Intensity – what’s the magnitude? 3. Duration – how long? 4. Location – where on the body? o Neural Encoding Physical Properties are turned into an electrical AP This is a binary process, but the combination of binary signals creates a complicated mix A closer look at Modality o Example Receptors Somatic Sensory on the Skin Photosensitive in the Eyes Auditory Pressure Sensors in the Ears o Divisions Five Major Modalities: 1. Touch 2. Hear 3. Taste 4. See 5. Smell Submodalities exist too: Eg: Touch can consist of Pain, Temperature, and Pressure o Specific Receptors 1) Vision – photoreceptors 2) Audition – mechanoreceptors 3) Somatic Sensation – mechanoreceptors, thermoreceptors, and nocireceptors 4) Taste – chemoreceptors 5) Smell – chemoreceptors 6) Proprioception – chemoreceptors, mechanoreceptors, and nocireceptors o Each modality has a specific and discrete system and pathway The Subnuclei of the Thalamus is a common relay point After this relay, they terminate in particular regions of the Cortex Specific Systems o 1. Somatic Sensory Overview Skin and Joints Submodalities o A. Touch/Pressure o B. Temperature o C. Pain Assessing I) Modality (Receptors) o A. Mechanoreceptors (respond to touch, the pressure) Pacinian Corpuscles, Meissner Corpuscles – nerve ending are covered and surrounded by gelatinous substance Merkel Disk, Pacinian Corpuscles – more superficial, not deep Hair Follicle – wrapped around, not a free ending o B. Thermoreceptors Has myelinated (superficial) and unmyelinated (deep) for rapid and slow response Both are branched and free at endings o C. Noci (Pain) Receptors Has myelinated (superficial) and unmyelinated (deep) for rapid and slow response Both are branched and free at the ending II) Intensity o Threshold is important to consider – minimal stimulus that elicits a response The pressure/heat/pain is converted into an electrical signal Consider Pressure o Each neuron has a trigger zone (comparable to the axon hillock) Cell Body in Dorsal Ganglion o Receptor Potential is a Passive Charge Any AP that is induced travels all the way to the Spinal Cord o Has two components to consider: 1] Frequency Code The more intense a signal is, the more it elicits AP’s 2] Population Code The sensors begin to recruit other local neurons November 2, 2015 Sensory Systems Continued Specific Systems o 1. Somatic Sensory Assessing I) Modality (Receptors) II) Intensity III) Location o How does the brain encode where the sensation occurred on your body? o Two Aspects 1. Field of Receptor Your nerves a field in which they can be activated Deep vs. Superficial o Deep have a wider field but need more intensity to fire o Superficial are much more specific and pointed Examples: o Meissner’s Corpuscles – hand, superficial receptors o Pacinian Corpuscles – hand, deep receptors 2. Density of Receptors How many receptors are present in a given area? Two Point Discrimination technique o Allows for more exact and specific response in some areas o Field Depth As the neurons synapse, continuing up the body to the brain, each successive neuron’s field is the aggregation of the previous neuron Eg: o Primary neuron from the skin has a singular, relatively small field of receptor o Secondary neuron has multiple primary neurons synapsing on it, so its field is the sum of the primaries’ o Dermatomes – sensory areas served by each spinal nerve, dorsal root, and spinal segment Divided up into segments IV) Duration o Adaptation – all sensory neurons adapt, in essence habituating the input (getting used to it) Occurs in all sensory Neurons Results in the decreased frequency of action potential, amidst continuous stimulation Measuring the Passive Potential entering the sensory neuron, we see a small dip that occurs despite continued stimulus o Two Types of Adaptation 1) Slow Adapting Gives tonic information (small and consistent) Diagram: o Upon coming down, fewer AP can occur 2) Rapid Adapting Trangent Information (long and sustained) Hump and the back to baseline (passive response) o So while at baseline, no AP can occur o Practical Application - You’re wearing a shirt – it is constantly and always touching you So you’d think it would constantly result in Sensation o But in fact you become used to it and don’t think about it But when you move, you notice it again Displays the interplay of Rapid and Slow Adapting Receptors Aspects of Touch with All Components Considered Size of Receptive Field – large vs. small Adaptation – fast vs. slow Table o All aspect are represented and present Primary Afferent Neuron Styles Names o Myelinated Afferent Neurons are labeled “A” neurons, with α, β, δ o “C” are unmyelinated o Chart Temperature and Pain o Done by the smaller neurons (Aδ and C) Touch and Sensation o All myelinated o Aδ is largest, has Proprioceptors that affect Skeletal Muscles o Aβ is slightly smaller, has Mechanoreceptors that innervate on skin Breakdown o Mehcano – Aβ o Thermo – C, Delta (δ) o Noci – Delta (δ) and C C5 is highly involved with pain Neural Pathways for the Somatic Sensory System Pathways Overview o Primary Sensory Neuron Overview These are First Order Bodies are in the dorsal root ganglia Peripheral Nervous System end is the receptor Central Nervous System End is the Axon Terminal Travels from sensory point to another neuron o Two Main Pathways 1) Dorsal Column-Medial Lemniscus Pathway Mechanoreceptors 2 Order is present in the Medulla Tract goes through spinal cord 2) Spino-Thalamic Pathway Thermoreceptors and Nociceptors nd 2 Order is present in the Dorsal Horn Dorsal Column Medial Lemniscus o Ipsolateral projection (same side, doesn’t cross from Primary to Secondary) o Synapses in the Medulla Specifically, the Gracile and Cuneate nuclei o The Second order then crosses, eventually synapsing on the Thalamus Specifically the Ventral Posterior Nucleus Crosses contralaterally here o From the Thalamus a tertiary neuron synapses on the cortex It does so on the Primary Sensory Cortex This Cortex is contralateral to the reception region, ipsilateral to the thalamus synapse Spinal-Thalamic Pathway o Primary Neurons Synapses Their cell bodies are in the Dorsal Root Ganglia They synapse in the Dorsal Horn in the Spinal Cord o The Secondary neuron then crosses contralaterally and synapses on the Thalamus Specifically the Ventral Posterior Nucleus (Same spot as the Dorsal Column Medial Lemniscus) o The third then goes from the Thalamus to the Primary Sensory Cortex This is contralateral to perception location, but ipsilateral to the thalamus connection Commonalities o 1. The Second Order Neuron Crosses Contralaterally o 2. The Second Order Neuron Synapses on the Thalamus o 3. The Third Order Neuron goes from the Thalamus to the Primary Somatic Sensory Cortex November 4, 2015 Sensory Systems Continued – Somatosensory Specific Systems o 1. Somatic Sensory Assessing I) Modality (Receptors) II) Intensity III) Location IV) Duration Aspects of Touch with All Components Considered Primary Afferent Neuron Styles Neural Pathways for the Somatic Sensory System Somatic Sensory Cortex Somatatopic Organization Post Central Gyrus and Central Sulcus of the Brain is where the tertiary neurons synapse in order to affect movement and sensation This region is spatially represented in the brain and body, with groups of neurons regionally represented in the gyrus o This is known as the somatotopic representation Lateral Inhibition in the Somatic Sensory System How does the body account for the accumulating Fields of Receptors? o Each field of receptor increases as more neurons synapse – secondary is summation of primary, tertiary is summation of secondary, etc. o But the body needs to refine the signal – if all neurons were activated, the signals would be overwhelming The method for refining and limiting is called Lateral Inhibition o Does so through the “Center-Surround” Receptor Interaction Center Receptor – the excitatory, targeted receptor neuron Surround Receptor – inhibitory, surrounding region o Diagram Feed Forward and Feedback Inhibition through Laterally Synapsed Cells o 2. Auditory System Physical Aspects of Sound Works with Air Compression (Increased density, increased pressure) and Rarefication (decreases density, decreased pressure) o This back and forth actions results in waves Frequency – pitch/tone Amplitude – loudness Physical Aspects of the Ear Ear Structure o Rough Components: 1. Outer – pinna and auditory canal 2. Middle – tympanic membrane (ear drum) and ossicles (connect tympanic membrane to the inner ear) 3. Inner – vestibular apparatus and cochlea o Specific Things to Note Ossicles – small bones connecting tympanic membrane to the Oval Window (portion of the inner ear) They essentially “play drums” on the inner ear in response to ear drum movement Oval Window – small portion of the inner ear where the tympanic membrane and inner ear are connected by the ossicles Tympanic Membrane – the ear drum; first registers the auditory vibrations Cochlea – inner ear; transduces physical signal Cochlea o Coiled, snail-like Tube o Contains 3 Fluid Filled Regions Names 1. Scala Vestibuli (large, connected to Tympani, contains perilymph) 2. Scala Tympani (large, connected to vestibule, contains perilymph) 3. Scala Media (smaller, stands alone, contains endophymph) o Contains organ of corti o Organ of Corti (Contained within the Smaller Chamber, the Scala Media – the Scala Media is isolated from the other two) 1. Attached to Basilar Membrane (part of the Scala Media) On the bottom of the Scala Media 2. Hair Cells in the Membrane react and move Have specialized Cilia that are attached to the Hair Cells’ and the Tectorial Membrane (cilia known as Stereocilia) These cells synapse on the Spiral Ganglia, creating the Auditory Nerve 3. Cilia interact with the Tectorial Membrane o Hair Cells Outer – most amplifies the sound Inner – most responsible for hearing Transduction of Sound General Process o Entering the Cochlea (involves the Tympanic Membrane, the Ossicles, and the Oval Window) o Fluid Waves – the physical waves become part of the fluid wave when it enters the Scala Vestibuli o Oscillation in Basilar Membrane – basilar membrane in the Organ of Corti in the Scala Media o Movement of Hair Cells – Hair cells just above the Basilar Membrane begin to move in response to basilar movement o Movement of Cilia – cilia on the hair cells begin to oscillate and move in response to the hair cells, influencing the tectorial membrane, a stiffer membrane Stereo Cilia Movement o Diagram Mechano-Electric Aspect of Transduction o Presence of Mechanically Activated Potassium channels on the tips of the Stereocilia (respond to movement) Causes depolarization In this case, the K equilibrium is equal and the mV is -45, so K flows in when the channels open The Cilia Oscillate back and forth, pulling the channels Open when moving towards the long cilia (diagram) Closed when open towards the shorter cilia (diagram) Depolarization from Potassium opens Calcium channels which mediates the release of
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