what should i study for neuroanatomy?
is it enough to study from road map neuroscience?
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INTRODUCTION TO NEUROSCIENCE


Gross Brain Development:

• Rhombencephalon (Hindbrain)
  • Myelencephalon ------> Medulla Oblongata
  • Metencephalon ------>Pons, Cerebellum
• Mesencephalon (Midbrain) ------> Midbrain
• Prosencephalon (Forebrain) ------> Diencephalon + Telencephalon
  • Diencephalon
    • Thalamus
    • Epithalamus
    • Hypothalamus
    • Subthalamus
  • Telencephalon ------> Cerebral Hemispheres

Five Main Divisions to the Central Nervous System:

• Spinal Chord -- 31 pairs of spinal nerves give SEGMENTATION to the body
  • Dorsal Root ------> Dermatomes
  • Ventral Root ------> Myotomes
  • Developmentally, they originate from formation of the somites.
• Brainstem -- divided into three divisions
  • Medulla Oblongata (Myelencephalon): Associated with part of CN XIII, and CN IX, X, XI, and XII.
  • Pons (Metencephalon): Associated with CN V, VI, VII, and part of CN VIII.
  • Midbrain (Mesencephalon): Associated with CN III and IV
• Cerebellum: Coordination of skeletal muscle activity
• Diencephalon: Integrates and routes sensory and motor information
  • Dorsal Thalamus
  • Subthalamus
  • Epithalamus
  • Hypothalamus
• Cerebral Hemispheres (Telencephalon): Higher perceptual, cognitive, and motor functions
  • White Matter -- myelinated, in the center
  • Grey Matter: Cell bodies composing the cerebral cortex.
  • Lateral Ventricles: Filled with cerebrospinal fluid.
  • Basal Ganglia: Important role in modulating motor activity and emotional tone.

FRONTAL LOBES: PRE-CENTRAL GYRUS, Cerebral cortex in front of the Central Sulcus. Responsible for effecting voluntary motor activities, and foresight and judgment.
SENSORY LOBES: POST-CENTRAL GYRUS. The other cerebrocortical lobes are responsible for one or another sensory

• PARIETAL LOBES -- somatosensory
• TEMPORAL LOBES -- auditory
• OCCIPITAL LOBES -- visual

CROSSING OF FUNCTION: The left side of the brain controls the right half of the body.

• Stimulation of the PRE-CENTRAL GYRUS will cause motor stimulation on the opposite side of the body.
• Stimulation of the POST-CENTRAL GYRUS will cause sensation to occur on the opposite side of the body.

SENSORY TRACTS: Sensory highways go up the spinal cord, converge on the thalamus, and are then distributed to the proper location in the Post-Central Gyri of the opposite side of the body.

• There are considered to be two different sensory systems:
  • Primary Sensory Tracts -- somatic sensation
  • Discriminative Touch and Proprioception information.

MOTOR TRACTS: There are two different motor tracts that convey information from the Pre-Central Gyri to the destination motor units.

• Corticospinal Fiber System: Travels down spinal cord to influence motor units on the opposite side of the body.
• Corticobulbar Fiber System: Influences the head and neck via the four cranial nerves that provide parasympathetic motor innervation to the head and beck region.

NEUROHISTOLOGY


SANTIAGO RAMON Y CAJAL: He came up with evidence that nerve fibers are not continuous, but rather contiguous, and that synapses separate them.

• He asserted the polarity of cells, with dendrites receiving and axons delivering.
• Also established the neuronal growth occurs at the proximal stump (nearest the cell body) during development, and not at the distal stump.

CONTENTS OF THE NEURON SOMA: Only those things beyond the obvious.

• NISSL BODIES: Clusters of basophilic Rough ER, found in abundance in the neuron soma.
• Phagosomes: Waste-containing vacuoles that fuse with primary lysosomes to form secondary lysosomes.
• DENSE BODY: A tertiary lysosome, or a lysosomes that has already degraded much of its contents, but has non-digestible materials remaining.
  • Dense bodies contain Lipofuscin, which tends to accumulate with age.

DENDRITES:

• They generally develop after the axons.
• NO Golgi apparatus, and Nissl Bodies (i.e. Rough ER) diminish as you get away from the soma.
• Microtubules: The orientation of microtubules in dendrites is mixed -- both plus to minus and minus to plus.

AXONS:

• Axon Hillock is the initial segment of the axon, as it narrows down from the soma.
  • Nissl substances and Golgi can still be found at the hillock, but diminish as you move down the axon.
• Myelin Segments:
  • Node of Ranvier: The region of saltatory conduction where there is no myelin.
    • It is rich in Na+ channels.
  • Internode: The myelinated regions between nodes of Ranvier.
    • They are rich in K+ Channels.
  • Paranode: The region right next to a node of Ranvier.
• Microtubules and Neurofilaments: Histologically, they predominate throughout the axon.
  • For Microtubules, the plus-end points away from the cell body.
  • Mitochondria and smooth ER can also be found in axon. Other organelles are absent.
• AXOLEMMA: Membrane of the axon.

AXONAL TRANSPORT:

• Anterograde Transport: Movement away from the soma, toward the axon terminal.
  • Fast Anterograde Transport: 200-400 mm / day. This is the majority of standard protein transport, of stuff from the Rough ER.
    • Movement occurs in vesicles
    • Kinesin is required for transport of these vesicles. Kinesin is the plus-end microtubule motor protein.
    • ATP is therefore required for this movement, as Kinesin is an ATPase.
    • Cytoskeletal Proteins are not moved by this mechanism.
  • Slow Anterograde Transport:
    • Slow Component A: Moves primarily alpha-tubulin and beta-tubulin.
      • Proteins transported by this mechanism are synthesized on free polysomes in the soma.
      • Dynamin is the name of the microtubule motor protein that functions in slow-component A.
    • Slow Component B: Moves about 200 different polypeptides.
      • Proteins include actin, spectrin, clathrin, and others.
      • Motor mechanism may utilize actin/myosin.
      • Calcium-dependent proteases function to disassemble the structure so that proteins can be utilized at their destination.
    • Slow Component C: Not much is known about Slow Component C.
• Retrograde Transport: Movement toward the soma.
  • TWO FUNCTIONS:
    • Reprocessing or recycling of endogenous molecules.
    • A way for the neuron to obtain information about the periphery (as in trophic factors)
  • Molecules transported: NGF, neurotoxins, viruses
  • horse radish peroxidase = a retrograde tracer molecule.
  • Dynein moves things from the plus to the minus end of microtubules and is therefore responsible for retrograde transport.

NEUROPIL: The interconnected and interwoven processes of dendrites, axons, and glia. The neuronal environment.
Distinguishing Axons and Dendrites Histologically:

• Dendrites have a homogenous collection of microtubules, while axons have them in clumps.
• Axons may be myelinated. Dendrites aren't.
• The presence of synaptic vesicle indicates that it is an axon.

Types / Classifications of Neurons:

• According to number of processes
  • Unipolar -- have a single process that may give rise many branches.
    • One of those branches may serve as the axon while the other ones serve as the dendrites.
    • Distribution: The Parasympathetic cranial nerves
  • Pseudounipolar: Having the single process come off a stem attached to the soma.
    • Distribution: Dorsal Root Ganglia.
  • Bipolar: Having a single axon and single dendrite coming out of the cell body.
    • Distribution: Visual, Olfactory, Auditory, and Vestibular centers.
  • Multipolar: Most neurons. Multiple Axons and Dendrites
    • Fusiform: Web-like
    • Stellate: Star-shaped
    • Pyramidal: Containing an apical dendrite, basal dendrites, and an axon.
    • Polyhedral: As in motor horn of spinal cord, containing a single axon and multiple web-like dendrites.
• According to function: Sensory / Motor
  • Sensory: The majority of neurons.
  • Motor: (The cell bodies are) found in three discrete places.
    • Anterior Horn of spinal cord
    • Purkinje cells of cerebellum
    • Parasympathetic cranial nerve nuclei in Brainstem
  • Associative: Interneurons, which make connection between other neurons.
• According to function: Mode of Action
  • Excitatory
  • Inhibitory
  • Both Excitatory and Inhibitory: Release neurotransmitters that excite some neurons but inhibit others.
• According to length
  • Golgi Type I: Long axons, as in PNS.
    • They are also called projection interneurons.
  • Golgi Type II: Short axons, as in CNS.
    • They are also called local interneurons.

ASTROCYTES: Star-like neuroglial (neural accessory) cells.

• Functions:
  • Supportive role
  • Insulate synapse from each other
  • Regulate extracellular pH, K+ concentration.
  • Induce formation of the blood-brain barrier
  • Interaction with immune system
  • Limited phagocytosis
• GLIOSIS / ASTROCYTOSIS: Astrocyte response to disease in te brain.
  • They proliferate and divide
  • They increase their concentration of GFAP-laden intermediate filaments.
  • They form a dense network termed a glial scar.
• Astrocyte Morphology / Histology
  • Glial Fibrils: The name of the intermediate filaments in astrocytes.
    • Glial Fibrillary Acidic Protein (GFAP): The intermediate filaments are made up of this protein, hence stains specific for GFAP will illuminate astrocytes.
  • There are no microtubules in mature astrocytes.
  • Astrocyte End-Feet: Help form the blood brain barrier.
    • They are expansions at the end of astrocytic processes.
    • Glial Limitans: The "layer" of end feet that is right up against brain blood-vessels.
  • Astrocytes are the largest of all the accessory neuronal cells.
• Two General Types of Astrocytes: The two types of astrocytes are really two morphological ends of a continuous spectrum.
  • Fibrous Astrocytes: Prominent in white matter.
    • They have long, straight processes.
    • They contain more glial fibrils than protoplasmic processes.
  • Protoplasmic Astrocytes: Prominent in grey matter.
    • They have wavy, thin processes.
• Special Types of Astrocytes
  • Bergmann Glial Cell: Found in cerebellum, they have processes that extend all the way to the pial membrane, similar to early development.
  • Muller Cell: Found in retina, sharing features with both astrocytes and ependymal cells.

OLIGODENDROCYTES: Makes myelin in the CNS, and can myelinate multiple internodes.

• Morphology:
  • They can have up to fifty processes coming off of them. Each myelin sheath connects back to the oligodendrocyte by a single process.
  • They have no intermediate filaments.
  • They are smaller than astrocytes but larger than microglia.
• ORIGIN: Neuroectodermal
• Two types of Oligodendrocytes:
  • Interfascicular Oligodendrocytes: Oligodendrocytes found along and in between the axons they myelinate.
    • They are dedicated to myelin production.
  • Satellite Oligodendrocytes: Oligodendrocytes found only in the grey matter of the CNS.
    • They are found next to the neuron cell body.
    • They do not make myelin.
    • Thought to play a role in the maintenance of the neuron they are associated with.

SCHWANN CELLS: Makes myelin in the PNS.

• The Schwann Cell is associated with the myelin that it forms.
• Each Schwann Cell myelinates only one internode.
• ORIGIN: Neural Crest Cell
• Morphology: They do have intermediate filaments.

SATELLITE CELLS: Forms a single layer around neuron soma, separating the soma from adjacent capillaries.

• They are morphologically similar to Schwann cells.
• They help to form the "Blood-Neuron Barrier" in the PNS.

MYELIN:

• FORMATION: It is formed from two membranes with cytoplasm in between. The two membranes juxtapose and role up like a jelly donut.
  • Major Dense Line: The union of the two cytoplasmic faces of the lipid bilayer.
    • It is thought to be formed by Myelin Basic Protein.
  • Inter period Line: The union of the two extracellular faces of the lipid bilayer.
    • It is thought to be formed by Proteolipid Protein.
• Mesaxons: The cytoplasmic loops of myelin that are closest to the axolemma. Basically, the first layer of myelin that is immediately adjacent to the axon.
• SALTATORY CONDUCTION: Myelin is high resistance, and current jumps from one node of Ranvier to the next. Advantages of Saltatory Conduction:
  • Higher conduction velocity at a much smaller nerve diameter.
  • Conserve tremendous amount of energy by concentrating Na+ channels at the Nodes of Ranvier, so that the Na/K ATPases don't have to work as hard.

MICROGLIAL CELLS: The macrophages of the brain. They phagocytose debris in the CNS.

• These cells can get infected with HIV in individuals with HIV-dementia (presumably a possible but not essential manifestation of AIDS).
• Developmental origin is thought to be mesodermal.
• Morphology: They are much smaller than Oligodendrocytes or Astrocytes.

MULTIPLE SCLEROSIS: Lack of myelin in cells. Auto-antibody attack against myelin.
EPENDYMAL CELLS: Specialized epithelial cells that line the ventricles of the brain.

• Morphology:
  • Cuboidal or Columnar Epithelium.
  • They have polarity, and have a junctional complex near the luminal side. Junctional complex consists of:
    • Gap Junctions
    • Fascia Adherens and Zonula Adherens, both of which completely encircle the cell.
    • Zonula Occludens which obliterates any space between cells.

TANYCYTES: Found interdigitating with ependymal cells, in the walls of the third ventricle.

• They are thought to be transporter molecules.
• They contain GFAP.

BLOOD-BRAIN BARRIER:

• Brain Arteries: They are covered by Astrocyte End-Feet and pia mater.
• Brain Capillaries: The primary barrier is the capillary endothelium which has tight junctions. Diffusion in and out of capillary is tightly regulated.
  • Basement Membrane surrounds the outside of the capillaries.
  • Astrocyte End-Feet are outside the basement membrane.

BRAIN MENINGES:

• Dura Mater: Attached to skull, made of collagen.
• Arachnoid Mater: Interdigitating fibers make it seem several layers of thick.
  • The arachnoid mater is avascular.
• Subarachnoid Space: Contains the cerebrospinal fluid.
  • Arachnoid Trabecula form a web-like structure in this space.
• Pia Mater: Adherent to the brain.
  • The pia mater is highly vascular.
  • It follows vessels into the brain, forming reflections off of them as they enter brain.
  • Glial Limitans is just deep to the pia mater, separating brain from vessels. It is made of astrocyte end-feet.

CEREBROSPINAL FLUID:

• Functions:
  • Removes waste products and drugs
  • Supports and cushions the brain against trauma.
  • Carries hormones from the hypothalamus.
• Contents: It is made primarily of choroid plexus, with some capillary ultrafiltrate (18%) and glucose oxidation products (12%).
• CHOROID PLEXUS: Contain numerous villi, made of ependymal cuboidal epithelial cells.
  • The Ependymal cells have a basement membrane, and beneath that is the stromal core, in which the blood vessels are found.
  • Each choroid plexus is supplied by an artery.

CEREBELLUM LAYERS:

• MOLECULAR LAYER: Outermost layer of grey matter, containing relatively few, unmyelinated fibers.
  • Basket Cells: They send out processes in the molecular layer that interconnect Purkinje cells.
• PURKINJE CELLS: Middle border layer containing huge neurons, that have fine dendrites and axons extending beyond.
  • Purkinje Dendrite extends into the molecular layer (outer layer), where they receive efferent signals from the cerebellar cell bodies.
  • Purkinje Axons extends into the granular layer (inner layer), where they relay efferent signals ultimately to the white matter of the cerebellar core.
    • Purkinje axons are the only efferent fibers coming out the cerebellum.
• GRANULAR LAYER: The innermost layer, containing numerous cells and containing axons that extend into the molecular layer to meet up with the Purkinje dendrites.
• WHITE MATTER: Beneath the granular layer is the white matter core of the cerebellum, which is the interface between the cerebellum and the brainstem.
  • All incoming fibers have multiple connection in white matter and then make their way up to the cerebellar cortex, via the Purkinje cells.
  • Outgoing fibers go back to the white matter and down the brainstem, once again via Purkinje cells.

DORSAL ROOT GANGLION: Consists of pseudounipolar cells on the dorsal root (intervertebral foramen) of the spinal column. Both processes of a dorsal root ganglion cells are considered to be axons. Dorsal root ganglia are sensory neurons.

• Central Process: Transmits the sensory information into spinal column.
• Peripheral Process: Receives information from the periphery at the respective dermatomal level.

LAYERS OF THE RETINA: From the first layer that the light contacts, to the last layer that it contacts.

• Choroid: The material between the sclera and the beginning of the retina, through which the light travels.
• Pigmented Epithelium: Pigments in this layer absorbs a lot of the light initially.
  • It also supplies Vitamin-A to (and exchanges it with) the photoreceptor cells.
• Outer Segment: Contains the outer segment of rods and cones.
• Inner Segment: Containing the inner segment of rods and cones.
• Outer Nuclear Layer: Contains the nuclei of the rods and cones.
• Outer Plexiform Layer: Contains:
  • Horizontal Cells
  • Bipolar Cells
  • Processes and synapses from the rods and cones.
• Inner Nuclear Layer: Contains the nuclei and soma of the Bipolar, Amacrine, and Horizontal cells.
• Inner Plexiform Layer: Contains processes and synapses from the Bipolar, Amacrine, and Horizontal cells.
• Ganglion Cell Layer: Contains the Ganglion Cells, which ultimately converge on the Optic Nerve.
• Nerve Fiber Layer: Contains the axons of ganglion cells.
• Inner Limiting Membrane

NERVE SYNAPSES


ELECTRICAL SYNAPSES: A signal is passed from one neuron to another by the passive diffusion of electrical charge.

• General properties
  • They are only excitatory.
  • They are less common than chemical synapses.
  • Electrical synapses have cytoplasmic continuity between cells, formed by gap junctions.
  • Electrical synapses can conduct action potentials in both directions.
  • Electrical conduction of a signal is virtually instantaneous, while a chemical synapse has a delay time.
• Development: Electrical synapses are prevalent during development.
• Gap Junction: Structure is six cylindrical proteins, one each cell membrane, aligned in a circle such that they form a hole between the two cells.
  • Gap Junctions can exist in the open or closed state. The state of the junction is influenced by Ca+2, neurotransmitters, etc.

THE PRESYNAPSE:

• Bouton: The bulb-like structure formed at the axon terminal.
• Quantal Unit: The constant number of neurotransmitter molecules found in a single synaptic vesicle.
• Active Zone: The electron-dense end of an axon terminal, that extends from the plasma membrane to the synaptic vesicles.
• Three Proteins control the release of neurotransmitters in synaptic vesicles
  • Actin + Spectrin: Form the active zone cytoskeleton, and hold the synaptic vesicles in place.
  • Synapsin: Cross-links synaptic vesicles with the cytoskeleton of the active zone.
    • STRUCTURE: Phosphoprotein with globular head and fan-like tail.
      • Head: Binds other synapsin heads or actin filaments.
      • Tail: Binds the synaptic vesicles.
  • Dense Projections helps guide released synaptic vesicles to the right part of the plasma membrane.
• Synaptic Vesicles: They are acidic. Protons are pumped into the vesicle by an ATPase.
  • The acid pH creates a gradient so that neurotransmitter can get imported into the vesicles.
  • It is thought the acid pH protonates neurotransmitters once they get in the vesicle, so they can't get back out.
• Fusion of Synaptic Vesicle with Pre-Synaptic Membrane:
  • Synaptobrevin and Syntaxin: May be essential for targeting and docking of vesicles.
  • Synaptotagmin: Calcium-dependent releasing protein, that facilitates fusion in presence of calcium, and prevents it in absence of calcium.

NEUROTRANSMISSION: The process of releasing neurotransmitter is calcium-mediated.

• Membrane Depolarizes.
• Voltage-Gated Ca+2 Channels open on pre-synaptic membrane.
• Ca+2 comes flooding into the pre-synaptic axon.
• Ca+2-Dependent Protein Kinases become activated in the presence of Ca+2. They phosphorylate targets to cause neurotransmitter release.
• Synapsin gets phosphorylated, which causes it to release the synaptic vesicle and let go of the actin filament.
• Synaptotagmin and other Vesicle-Releasing Proteins also get phosphorylated, which causes them to facilitate the fusion of the synaptic vesicles with the pre-synaptic membrane.

RECYCLING: Synaptic vesicles are recycled following their fusion with the plasma membrane, by continual pinocytosis.
THE SYNAPTIC CLEFT: 10-20 nm wide in the central nervous system.

• It contains filamentous materials that link the pre and post synapse together, and that may help prevent extracellular diffusion of the neurotransmitter.
• NEUROTRANSMISSION Across the Synaptic Cleft: Occurs by simple diffusion.

NEUROTRANSMITTER CLEARANCE: After affecting the post-synapse, the neurotransmitter is disposed of by one of three mechanisms.

• Degradation (as in Acetylcholinesterase)
• Diffusion
• Reuptake (as in Norepinephrine)

TYPES OF SYNAPSES: Synapses can be categorized by various means.

• Categorization by the types of cells synapsing:
  • Axo-Dendritic: An axon synapsing on a dendrite.
  • Axo-Somatic: An axon synapsing on the cell soma.
  • Axo-Axonal: An axon synapsing on another axon.
• Synapses based on synapse morphology: This is actually a continuum.
  • Type I Synapse: Found on Dendritic Spine and the smooth parts of neurons.
    • Prominent dense bodies and synaptic vesicles
    • Synapse contain a basement membrane.
  • Type II Synapse: Found on Dendritic shaft or cell body.
    • Dense bodies and synaptic vesicles less prominent.
    • Synapse does not contain a basement membrane.

Criteria for being a "Classical Neurotransmitter":

• The presynaptic neuron must synthesize it, or its precursor.
• It must be found in the nerve terminal
• The terminal should release the compound.
• Compound should bind with high affinity to post-synaptic membrane.
• The compound should cause the effects expected of neurotransmission at the post-synaptic membrane.
• The effects should be susceptible to antagonistic and/or agonistic drugs.
• The compound should be removed from post-synaptic membrane.

RECEPTORS: There are several sets of criteria that define a neurotransmitter receptor.

• Kinetic Criteria:
  • High affinity binding of the ligand
  • Saturable binding at low concentrations
  • First order kinetics
  • No other molecules should be involved
• Pharmacological Criteria:
  • Agonistic and antagonistic pharmacological effects
  • Binding is stereospecific
  • The pharmacological effect should be coupled temporally (in time) with the effect.
• Anatomical Criteria:
  • An organ tissue that shows no response to the neurotransmitter should not have the receptor.
  • Concentration of receptors should be appropriate for the concentration of neurotransmitters found in that region.
• Chemical Criteria:
  • Chemical structure
  • Antibodies can be made to it, and it should be able to be localized by immunocytochemistry
  • In Situ hybridization to isolate and localize the mRNA's that encode the receptor.

AMINO ACID NEUROTRANSMITTERS: These neurotransmitters function in the CNS and exhibit ionotropic effects. They all exhibit ionotropic effects on the post-synapse.

• GABA (gamma-Amino Butyric Acid): Inhibitory Neurotransmitter
  • SYNTHESIS: alpha-Ketoglutarate ------> GABA, via a transamination and then decarboxylation.
  • GABAA RECEPTOR: Opens a Cl--Channel which hyperpolarizes the membrane.
    • alpha-Domain: Principle site to which GABA Itself binds.
    • beta-Domain: Barbiturates bind to the beta-domain and have agonistic effects.
    • gamma-Domain: Benzodiazepine binds to the gamma-domain and ultimately has agonistic effects.
  • VALIUM: Benzodiazepine
    • It only will bind to the gamma-domain of the GABAA receptor.
    • It is thought to facilitate the binding of GABA to its receptor, as opposed to having straight agonistic effects in itself.
  • GABAB AUTORECEPTOR: Thought to decrease inward Ca+2 flux on presynapse, thereby inhibiting further GABA release.
  • REMOVAL:
    • GABA Reuptake is done by the presynapse and glial cells.
      • The presynapse reuptake transporter is a Na+/GABA Antiport ATPase.
    • GABA Degradation can occur by GABA alpha-Oxoglutarate Transaminase. Some drugs can block this degradation, thus enhancing GABA's effects.
• Glycine: Also causes the opening of Cl- channels on the post-synaptic membrane.
  • DISTRIBUTION: Glycine is a specific to certain regions of CNS:
    • Cerebellum
    • Retina
    • Brain Stem
    • Spinal Chord
  • SYNTHESIS: Serine ------> Glycine
  • GLYCINE RECEPTOR
    • Appear to be homologous with both nicotinic Ach receptor and GABAA Receptor.
  • Strychnine blocks Glycine receptors.
  • REMOVAL: The only known method of removal is reuptake. Degradation may also occur but details are not known.
• Glutamate and Aspartate: Both are excitatory Neurotransmitter in the CNS. Generally they work by opening Na+-Channels and depolarizing post-synapse membrane.
  • SYNTHESIS: Brain tissue makes them de novo. They do not diffuse into CNS neurons from the general circulation.
    • Glutaminase can make Glutamate in brain, via Glutamine ------> Glutamate
  • N-Methyl-D-Aspartate (NMDA) RECEPTOR: A Voltage-Gated and Ligand-Gated receptor, which has both metabotropic and ionotropic effects.
    • RESTING STATE: Magnesium is bound to the inside of the receptor, blocking current flow through it.
    • ACTIVATED: The effects of voltage-gating and ligand-gating are additive in the NMDA receptor.
      • VOLTAGE-ACTIVATION: Magnesium is driven out, and Ca+2 and Na+ can come in. These are the ionotropic effects, as this further depolarizes the membrane.
      • LIGAND-ACTIVATION: Binding of aspartate or glutamate facilitates even higher current flow and more calcium coming into the cell.
    • METABOTROPIC EFFECTS: Calcium, once inside, activates Ca+2-Dependent (calmodulin) Kinases
  • Glutamate Toxicity: High levels of glutamate are toxic.
    • Overstimulation of NMDA Receptor ------> Too much in Ca+2 in cell ------> Ca+2-dependent proteaases will produce free radicals and cause neuron death.
    • Aspartate would be similarly toxic, but it isn't present in high enough levels to ever be a threat.

Long-Term Potentiation: An enhanced response to a neurotransmitter, via a higher EPSP.

• Potentiation plays a role in learning.
• The enhanced response is thought to be mediated by NMDA-Receptors and Nitric Oxide.

AMINE NEUROTRANSMITTERS: CATECHOLAMINES (Generally Metabotropic)

• Dopamine:
  • SYNTHESIS:
    • Tyrosine Hydroxylase: Tyrosine ------> L-DOPA (Dihydroxyphenylalanine)
    • DOPA-Decarboxylase: L-DOPA ------> Dopamine
  • DISTRIBUTION: It is the most prominent catecholamine in the brain, found in the midbrain, through three neuronal tracts.
    • Nigrostriatal Tract: Initiation and execution of movement. Implicated in Parkinson's Disease
    • Mesolimbic-Mesocortical Tract: Emotions, thought organizations. Implicated in Schizophrenia.
    • Tuberoinfundibular System: Couples the hypothalamus to the pituitary. Dopamine gets put into portal circulation in this system.
  • DOPAMINE RECEPTORS: Dopamine has metabotropic receptors.
    • D1 RECEPTOR: Coupled to a G-Stimulatory Protein that stimulates adenylate cyclase ------> higher cAMP levels.
    • D2 RECEPTOR: Coupled to a G-Inhibitory Protein that inhibits adenylate cyclase ------> lower cAMP levels.
  • DOPAMINERGIC DRUGS: Lots of them, both agonistic and antagonistic.
  • REMOVAL: Two compounds will degrade all catecholamines:
    • Monoamine Oxidase (MAO): Several drugs inhibit this compound ------> higher catecholamine levels.
    • Catechol-O-Methyltransferase
• Norepinephrine:
  • SYNTHESIS: Dopamine beta-Hydroxylase: Dopamine ------> Norepinephrine
  • DISTRIBUTION:
    • In the CNS, Norepinephrine is more concentrated than dopamine in other parts of the brain (other than midbrain)
    • Norepinephrine is the main sympathetic neurotransmitter in the PNS.
  • REMOVAL: Norepinephrine is primarily removed by reuptake, although degradation also occurs.
• Epinephrine:
  • SYNTHESIS: Norepinephrine ------> Epinephrine via a methyltransferase.
  • DISTRIBUTION: Primarily secreted by adrenal medulla into bloodstream, but it is also found as a neurotransmitter in medulla, and maybe hypothalamus + retina.

AMINE NEUROTRANSMITTERS: OTHER AMINES (Generally Metabotropic)

• Serotonin (5-Hydroxytryptamine): Involved with appetite, thermoregulation, sleep, pain perception.
  • SYNTHESIS: It is synthesized from Tryptophan.
    • Tryptophan ------> 5-Hydroxytryptophan ------> Serotonin
  • DISTRIBUTION: In CNS, the medulla, pons, and midbrain.
  • SEROTONIN RECEPTORS: Metabotropic.
    • 5HT1-RECEPTOR: beta-Adrenergic Receptor, linked to adenylate cyclase.
    • 5HT2-RECEPTOR: alpha-Adrenergic Receptor, linked to Inositol Triphosphate (IP3) and Diacylglycerol (DAG).
  • DRUGS: Several, both antagonistic and agonistic.
    • Antidepressant Prozac = inhibit Serotonin reuptake.
    • LSD is a serotonin antagonist.
  • REMOVAL: Reuptake, plus monoamine oxidase.
• Histamine: Involved in arousal, mental disease, cardiovascular control, to name a few.
  • SYNTHESIS: It is synthesized from Histidine
    • L-Histidine Decarboxylase: Histidine ------> Histamine
  • DISTRIBUTION: Only hypothalamus
  • RECEPTORS:
    • H1 + H2 RECEPTORS: Metabotropic
    • H3 RECEPTOR: An Autoreceptor.
  • REMOVAL: Via monoamine oxidase.

NEUROPEPTIDES: Also called Cotransmitters or Neurohormones.

• How they differ from Amino Acid and Amine Neurotransmitters:
  • They are present in very low concentration
  • They are made from amino acids 3-100 residues long
  • They are found in association with other transmitters (i.e. not acting by themselves)
  • They may act at a distance (i.e. through a microcirculation)
  • They are degraded by peptidases. There is no reuptake.
  • They are propeptides, and they are generated by cleave of the precursors.
• HYPOTHALAMUS: A rich source for neuropeptides in the brain.
• RECEPTORS: The same neuropeptide can have multiple receptors (like hormones), and they are generally metabotropic.

ACETYLCHOLINE:

• DISTRIBUTION:
  • In the PNS, primary neurotransmitter in the Parasympathetic nervous system and at the skeletal neuromuscular junction.
  • In the brain there are five discrete functions, to be learned later.
• SYNTHESIS: Choline Acetyltransferase: Choline ------> Acetylcholine
• ACETYLCHOLINE RECEPTORS: There are multiple types of both the muscarinic and nicotinic type receptors.
  • MUSCARINIC RECEPTORS: Metabotropic Receptor
    • DRUGS:
      • Muscarine is an agonist to the receptor.
      • Atropine is an antagonist.
    • Activation of this receptor has slow excitatory onset.
    • Thalamus: Muscarinic receptors have slow inhibitory onset.
    • Effects are stimulatory or inhibitory, depending on the type of G-Protein attached.
  • NICOTINIC RECEPTORS: Ionotropic Receptor
    • DRUGS:
      • Nicotine is an agonist to the receptor.
      • Tubocurarine is an antagonist.
    • Activation of this receptor has rapid excitatory onset.
    • STRUCTURE: There are five separate subunits comprised of four different chains: 2 alpha, 1 beta, 1 gamma, 1 delta. The subunits form a Na+-Channel that opens which Acetylcholine binds.
• REMOVAL: Acetylcholinesterase. Reuptake is not significant.

NITRIC OXIDE: Important in communication between cells.

• SYNTHESIS: Nitric Oxide Synthetase
  • L-Arginine ------> Nitric Oxide + Citrulline
  • NADPH and Ca+2 are cofactors.
• FUNCTIONS:
  • Relaxation of smooth muscle vascular walls.
  • Contraction of GI Tract
  • Penile erection
  • A neurotransmitter
• Unique Properties:
  • It is not stored in vesicles.
  • It is used once synthesized, and it passes through cell membrane to reach target.
  • It binds to iron to modulate enzymatic activity.
• Long-Term Potentiation: NO is synthesized at the post-synapses and then diffuses backward to the presynapse, or so they think.

CARBON MONOXIDE: Synthesized by Heme Oxygenase. Little else is known.
METABOTROPIC RESPONSES: Response via a signal transduction pathway that ultimately changes metabolic behavior.

• Signal Transduction Pathways, for the 25th time:
  • beta-Adrenergic: cAMP.
    • Adenylate Cyclase ------> cAMP ------> Protein Kinase A ------> Target
  • alpha-Adrenergic: IP3 + DAG
    • Phospholipase C cuts Phosphatidylinositol-4,5-biphosphate into Inositol Triphosphate (IP3) and Diacylglycerol
    • IP3 then goes to ER where it opens Ca+2 Channels ------> influx of Ca+2 into cytoplasm.
    • IP3 activates Calcium-Dependent Protein Kinase C which then phosphorylates targets.
    • Lithium blocks the degradation of inositol phosphates.
  • Arachidonic Acid: It is released by the cell membrane Phospholipase A2. Arachidonic acid then leads to several short-lived metabolites:
    • Prostaglandins via cyclooxygenase
    • Leukotrienes via 5-lipoxygenase
    • These hydrophobic compounds interact with neighboring cells without going through a receptor.
• EFFECTS OF PROTEIN PHOSPHORYLATION:
  • Close K+ Channels: They can lead to closure of K+ channels ------> membrane depolarization and hence an excitatory effect.
  • Altered gene expression
  • Short Term Sensitization: Make the post-synapse more sensitive to certain neurotransmitters, such as Serotonin, for short-term.
  • Long Term Memory: Come genes that are up regulated by phosphorylation are believed to play an important role in long-term memory.

IONOTROPIC RESPONSES:

• Ligand-Gated Channels: They open Na+-Channels in response to binding ligand (such as ACh).
  • They are not voltage-sensitive and therefore cannot spread an action potential, but only initiate it at the post-synaptic membrane.
  • Voltage-gated channels are required to spread the AP.
  • Excitatory Ligand Gated Channels: Unlike voltage-gated channels, most of them are non-specific. They let Na+, Ca+2, and K+ through equally.
• In the CNS, about 10 signals (+1 mV each) are required to generate a post-synaptic action potential.
  • CNS resting potential is around -65mV and threshold is generally -55mV.
  • Summation of signals is required to accomplish this. One signal is insufficient.

INHIBITORY POST-SYNAPTIC POTENTIAL (IPSP): Hyperpolarization of the post-synaptic membrane in response to a neurotransmitter.

• Ligand-Gated Cl- Channels can be triggered open.
• A second messenger (metabotropic) that opens K+ Channels can also cause an IPSP (via K+ out ------> hyperpolarization).

EXCITATORY POST-SYNAPTIC POTENTIAL (EPSP): Depolarization of the post-synaptic membrane in response to a neurotransmitter.

• Na+ and Ca+2 ligand-gated channels will lead to EPSP.

GRAND POSTSYNAPTIC POTENTIAL and SUMMATION: The sum of all EPSP's and IPSP's generated in the soma, from multiple simultaneous in-coming signals.

• Spatial Summation: Summation of signals in space, due to juxtaposed or closely placed synapses on the same post-neuron.
• Temporal Summation: Summation of signal in time.
• It is the job of the cell body, at the axon hillock, to process and interpret the summation of positive and negative signals.
• FREQUENCY: The larger (more positive) the incoming signal is at the Axon Hillock, the faster it will fire action potentials. A larger incoming signal does not generate a stronger action potential -- only more action potentials in a faster time.

AXON HILLOCK: It has five different ion channels to achieve the function of encoding incoming signals and converting them into a firing frequency.

• "Delayed Rectifier" Voltage-Gated Potassium-Channel: Functions to repolarize the membrane.
  • It open in response to depolarization, but it does so more slowly than the Na+ channels.
• "Early" Voltage-Gated Potassium-Channel: Modulates the frequency of depolarization according to the strength of the stimulus.
  • STIMULUS SLIGHTLY ABOVE RESTING: The channel is open. It thus behaves like an A-Type K+ Channel (which this might be) and counteracts the Na+ current, slowing down the rate of depolarization.
  • STIMULUS SIGNIFICANTLY ABOVE RESTING: The channel is inactivated, so that there is no countercurrent to the Na+ channels, so that depolarizations occur more rapidly.
• Ca+2-Activated Potassium Channel: Spike Frequency Adaptation.
  • In response to high Ca+2, these channels are just plain open, hyperpolarizing the membrane and making it difficult (or impossible) to fire an action potential.
• Voltage-Gated Calcium Channel: A brief influx of Ca+2 occurs through these channels at each action potential.
  • This calcium contributes to spike frequency adaptation, when the level is high enough.
• Voltage-Gated Sodium Channel: Standard depolarizing kinda channel.

THE NEUROMUSCULAR JUNCTION


Somatic Efferent Motoneurons: Myelinated peripheral neurons that target skeletal muscle.

• Neuronal Cell-Type = Polygonal, Multipolar.
• Cell bodies in the ventral horn of the grey matter of the spinal column.

Visceral Efferent Motoneurons: Unmyelinated

• Cell bodies in various autonomy ganglia.

MOTOR UNIT: A single somatic motor neuron, plus all of the muscle fibers it supplies.

• Small motor units: Fine, precision control and less strength
• Large motor units: Gross motor control and greater strength

SYNAPSE MORPHOLOGY:

• Pre-Synaptic Boutons: As the nerve approaches the muscle, the myelin disappears and the nerve divides into multiple boutons.
  • The boutons generally lie along the middle of the muscle fiber.
  • They contain synaptic vesicles and numerous mitochondria.
    • Synaptic Vesicles are near the Active Zone
    • Mitochondria are away from the Active Zone.
  • The muscle cells have troughs (infoldings), and the presynaptic boutons of the motoneurons lie in those troughs.
• Acetylcholine Synthesis in Boutons:
  • Acetylcholine Synthesis occurs in the pre-synaptic boutons themselves.
  • Choline-Acetyltransferase is synthesized in the cell body and transported down the axon.
  • Choline is taken in from the ECF via an energy dependent Na+ cotransport mechanism, in the nerve terminals.
• Acetylcholine Receptors: They are present at the mouths of the junctional folds on the muscle membrane -- that portion closest to the presynaptic boutons.
  • They are present in very high concentration.

MINIATURE ENDPLATE POTENTIAL (MEPP): The potential created by a single quantum of acetylcholine, or one synaptic vesicle.

• One MEPP results in a muscle membrane depolarization of about 0.4mV
• A quantum contains about 5000 ACh-Molecules, and about 2000 ACh-Receptors are activated per MEPP.
  • 2 molecules of Ach bind to each receptor, so about 4000 Ach molecules contribute to each MEPP.
• Multiple MEPP's are required to depolarize a muscle membrane.

PROCESS OF MUSCLE STIMULATION:

• PRESYNAPSE
  • Action potential causes depolarization of pre-synaptic bouton.
  • This causes Voltage-Gated Ca+2 Channels to open on the pre-synaptic membrane, and Ca+2 comes pouring into the presynapse.
  • The Ca+2 then triggers the mobilization of the synaptic vesicles and ultimate exocytosis of acetylcholine.
    • Botulinum Toxin blocks release of acetylcholine from presynapse.0
  • About 15-250 quanta of acetylcholine are released, in 1-2 millisec.
• ACETYLCHOLINE RECEPTOR: Again -- five subunits, 2alpha,beta,gamma,delta
  • The two alpha-subunits both contain ACh-binding sites -- so two acetylcholine bind to each ACh-Receptor.
    • alpha-Bungarotoxin binds the alpha-subunits and blocks ACh from binding.
    • Both of the alpha-subunits must bind a molecule in order to effect the conformational change in the molecule.
  • ION CHANNEL: The cation channel in the middle of the acetylcholine receptor, when open, is equally permeable to Na+, K+, and Ca+2
• POSTSYNAPSE: Muscle Activation
  • 2 Acetylcholine molecules per receptor bind to the post-synaptic membrane.
  • The receptor changes conformation for a brief time and then changes back. This allows cations to flow through, depolarizing the membrane slightly.
    • Na+ contributes the most to the depolarization, because of its concentration gradient, although Ca+2 contributes too.
  • This triggers the standard Voltage-gated Na+ Channels on the muscle membrane. They finish the depolarization, creating an action potential in the muscle membrane.
  • The depolarization spreads throughout the Sarcolemma and triggers voltage-gated Ca+2 channels in the SR to open, leaking Ca+2 into the muscle fibers and effecting muscle contraction.
• SUMMATION: Muscles are not affected by summation. A single motoneuron action potential ------> a single muscle contraction.
• Acetylcholine REMOVAL: Acetylcholinesterase.
  • Neostigmine: It blocks acetylcholinesterase.
  • Some ACh is also removed by simple diffusion.
  • TROPHIC FACTORS
    
    
    ANTEROGRADE TROPHIC EFFECTS: A cell secreting substances onto a target cell, thereby effecting a change in the target cell. This is basically a hormonal paracrine (cell to neighboring cell) interaction.
    • Mediated primarily by classical neurotransmitters.
    • Atrophy and Hypertrophy of muscles (where the muscle is subjected a trophic effect) is an example, although this may be due to electrical stimulation rather than to a substance.
      • Working the muscle plays a role, but electrical stimulation of a muscle alone, without the contraction, can prevent a muscle from undergoing atrophy.
    • Regulating the levels of substances in the target cells (such as neurotransmitter in the target cell) is a primary function of anterograde trophism.
    RETROGRADE TROPHIC EFFECTS: All other important effects are retrograde -- the target cell secreting some substance onto the axonal process. Then the axonal process takes it back to the soma, via retrograde transport, where it elicits some response in the cell body.
    • Neurotrophins is the catch-term for all compounds that elicit retrograde trophic effects.
    NERVE GROWTH FACTOR (NGF): The one and only coolest retrograde neurotrophin.
    • DEVELOPMENT: As nerves grow, the final number of neurons that will ultimately innervate a target is determined by the target. This determination is mediated by NGF.
      • NGF by itself is all that is necessary for a neuron to survive. If a target substance secretes NGF, then the neuron adjacent to it will survive.
      • Antibodies to NGF will cause neuronal developmental death, as NGF is unavailable.
      • Neuronal Morphology: Trophic Factors affect neuronal shape and size during development -- especially the complexity of the dendritic tree.
    • • • The larger the target mass, the higher the dendritic complexity. Supplementing a neuron with extra NGF can also increase dendritic complexity.
    • WALLERIAN DEGENERATION: Death of a nerve axon distal to the point of lesion. Loss of NGF from target is the central cause of this neuronal death.
      • Axotomy: Cutting a nerve is known as axotomy. It will make the segment of axon distal to the lesion die.
        • Axotomy also makes the cell body swell, and Rough ER is lost, a process called Chromatolysis because of the RER staining properties.
      • Chromatolysis: The structural changes to the cell body resulting from axotomy.
        • NGF prevents Chromatolysis.
        • Chromatolysis is caused by an absence of NGF. This can be from a loss of axonal transport or loss of contact with the target.
        • So, the nerve, now severed from its target, no longer as the effects of NGF acting on its cell soma.
      • The loss of NGF can be trans-synaptic and spread to neighboring neurons.
      • SUPPORT CELLS: With a nerve injury, Schwann Cells dramatically increase NGF production.
        • They are stimulated to do that by interleukins released from macrophages at the point of injury.
        • This can help explain how cell death is prevented, in cases when it is prevented.
        • Because of the role of Schwann cells, lesions closest to the cell body of a neuron are most likely to result in the neurons death.
    • INNERVATION DENSITY: NGF also correlates with sympathetic innervation density, i.e. the number of neuroeffectors innervating a target organ or muscle.
    • COLLATERAL SPROUTING: NGF mediates recovery from limited nerve damage, by adjacent neurons extending processes to the denervated area.
      • This appears to be mediated by NGF and other neurotrophins.
      • This is an important in Polio where many muscles are partially denervated.
    OTHER NEUROTROPHINS OF THE NGF FAMILY: These molecules have similar sequences as and bind the same receptors as NGF.
    • Brain Derived Neurotrophic Factor (BNDF)
    • Neurotrophin 3 (NT3)
    NGF RECEPTORS: There are two NGF-type receptors. Both are required on the nerve-membrane for high affinity binding of NGF.
    • Low-Affinity NGF Receptor (LNGFR):
    • Tyrosine Kinase NGF Receptor: Autophosphorylating tyrosine kinase cascade.
      • This receptor has three genetic isoforms. BNDF, NT3, and NGF differ in which forms they are receptive to.
      • The genes are protooncogenes.
    CILIARY NEUROTROPHIC FACTOR (CNTF): Another neurotrophin that does not belong to the NGF family.
    • FNXN: It mediates the switch from noradrenergic to cholinergic innervation of sympathetic neurons on eccrine sweat glands.
    • Nearly all sympathetic neurons secrete NorE, except those innervating eccrine sweat glands, which secrete Acetylcholine.
    • The nerves that innervate these glands originally secreted NorE, and it wasn't until they contacted the target glands that they switched to Cholinergic.
    Amyotrophic Lateral Sclerosis (ALS): A loss of anterograde trophic effects to skeletal muscles, from lower motor neurons.
    • Lateral Sclerosis = hardening and gliosis of corticospinal tracts along lateral spinal cord.
    • Recombinant CNTF is currently being tried as a potential therapy.

THE AUTONOMIC NERVOUS SYSTEM


Autonomic Reflex: Autonomic efferent fibers can be initiated in response to different types of afferent signals:

• Visceral Afferent Fibers: Transmission of visceral pressure, stretch, and noxious-stimuli.
  • Cell bodies of these sensory neurons are located in the sensory ganglia of CN VII, IX, and X.
  • Enteroreceptors are specialized fibers to transmit these visceral signals.
• Somatic Afferent Fibers: Temperature, pain, and light.
• Cognitive Input from higher learning centers: Perceived threats, anxiety, excitement, and sexual arousal can all influence autonomic motor responses.

AUTONOMIC -vs- SOMATIC NERVOUS SYSTEMS:

• The autonomic system generally acts slower.
• The last inter-neuronal synapse of a somatic nerve is in the CNS (in the spinal column), while the last inter-neuronal synapse of an autonomic nerve is in a peripheral ganglion.

PropertyPARASYMPATHETICSYMPATHETICAnatomical OriginCRANIO-SACRAL: CN III, VII, IX, X, and the Pelvic Splanchnic NervesTHORACO-LUMBARPreganglion Axon : Postganglionic AxonLong Preganglion Axon and short postganglionic Axon; Ratio is nearly 1:1, yielding discrete effectsShort Preganglionic Axon and long postganglionic axon; ratio is 1:many, yielding diffuse effectsLocation of Upper Cell BodiesBrainstem nuclei and sacral segmentsIntermediolateral segments of the thoracolumbar spinal cordLocation of Interneuronal GangliaIn or very near the target organParavertebral and Prevertebral Ganglia, far away from target organsPrinciple NeurotransmitterAcetylcholineNorepinephrineOther Neurotransmitters foundVasoactive Intestinal Peptide (VIP), which results in synthesis of NO ------> vasodilationNeuropeptide Y
Somatostatin Enkephalins
Principle Neurotransmitter Receptors at target organs:Muscarinic acetylcholine receptors, at the end organs. Also Muscarinic Autoreceptors on the postganglionic terminal, providing feedback inhibition for release of Ach.
beta-Adrenergic Receptors (cAMP secondary pathway) alpha-Adrenergic Receptors (IP3/DAG secondary pathway)
Neurotransmitter InactivationAcetylcholinesterase is the primary wayReuptake is the primary method of getting rid of NorE.Ocular ReflexMiosis: constriction of pupil is a reflex to light
Accommodation: Initiated by afferent signals from optic nerve ------> Contract ciliary muscle ------> increase natural curvature of lens ------> focus for near vision Lacrimation via Facial VII.
Pupillary Dilation: Radial smooth muscle of pupil contracts
Ciliary Muscle Relaxation These neurons for these reflexes come from Superior Cervical Ganglion ------> Carotid Plexus
Digestive ReflexSalivation via Chorda Tympani (VII) and Lingual (IX)
General increase in GI smooth muscle tone Liver promotion of glycogenesis
Salivation via sympathetics from external carotid plexus
General Relaxation of GI smooth muscle tone
Liver induction of glycogenolysis and gluconeogenesis Anal Sphincter contraction
Respiratory ReflexBronchoconstriction Vagal innervation of smooth muscle in trachea and bronchi.
BronchodilationCardiac ReflexDecrease heart rate by vagal innervation SA nodeIncrease heart rate by innervation of SA Node Increase heart contractility
Sexual ReflexPenile Erection -- vasodilation involved NO and possible VIPEjaculation
SYMPATHETIC NERVOUS SYSTEM:

• Pathway of sympathetic spinal nerves out of the spinal cord:
  • From spinal cord, the dorsal root and ventral root of each sympathetic nerve join to form the White Communicating Ramus.
  • The White Communicating Ramus goes to the Paravertebral Ganglia, on either side of the spinal cord.
  • PREGANGLIONIC NERVE: Once in the Paravertebral Chain, it can do one of four things:
    • It can go up to a level rostral to the current level (to provide sympathetics to cranial region)
    • It can go down to a level caudal to the current level (to provide sympathetics to sacral region)
    • It can synapse with a ganglion cell located in the chain ganglia.
    • It can go straight through the chain without synapsing, thereby forming a splanchnic nerve which will go onto the Prevertebral Ganglia.
      • Prevertebral Ganglia: The prevertebral ganglia receive preganglionics from the Thoracic Splanchnic Nerves.
        • There are four major prevertebral ganglia:
          • Celiac Ganglion
          • Superior Mesenteric Ganglion
          • Inferior Mesenteric Ganglion
          • Aorticorenal Ganglion
        • There are four major thoracic splanchnic nerves, which go straight through the paravertebral chain to synapse in the prevertebral ganglia.
          • Greater Thoracic Splanchnic (T10)
          • Lesser Thoracic Splanchnic (T11)
          • Least Thoracic Splanchnic (T12)
  • POSTGANGLIONIC NERVE: For those nerves that synapse in the paravertebral chain, they can do one of two things afterwards:
    • It can form a grey communicating ramus which then goes on to form a spinal nerve and provide sympathetic innervation to the appropriate dermatomal level.
      • Many blood vessels, sweat glands, hair follicle, and piloreceptors are innervated in this way.
    • It can leave the paravertebral ganglion and go straight to its target organ. This happens mainly in the cranial and sacral regions.
• ADRENAL MEDULLA: Releases 80% Epi and 20% NorEpi into bloodstream.
  • It is innervated by sympathetic preganglionics, which have come by way of the celiac ganglion, but they didn't synapse there.
  • It is sympathetic cholinergic, with nicotinic ganglionic acetylcholine receptors.
• ADRENERGIC RECEPTORS:
  • Beta Receptors: Activated by Isoproterenol
    • beta1-Receptor: Sympathetics in heart and kidney (renin release) -- they respond equally to both epinephrine and NorE
    • beta2-Receptor: All other tissues except adipocytes -- responds primarily to NorE
    • beta3-Receptor: Adipocytes
  • Alpha Receptors: Activated by Phenylephrine

GANGLIONIC NICOTINIC CHOLINERGIC RECEPTORS: Both sympathetic and parasympathetic neurons use acetylcholine. Their receptors are of the nicotinic type, but they are different structurally in that they respond differently to drugs.
GROUND PLEXUS: Autonomic postganglionics are unmyelinated. Near the target organ they divide to form a meshwork-like web called a ground-plexus.
Axonal Varicosity: The autonomic axon becomes wider near the target.
NEUROEFFECTOR JUNCTION: The name of an autonomic synapse. It is not proper to call it a synapse.

• It is not called a synapse because there are no ultrastructural membrane specializations between the neuron and the target cell. Thus it not a synapse.
• Prejunctional Element: Autonomic name for the presynapse.
• Postjunctional Element: Autonomic name for the postsynapse.

Autonomic Tone: The continual visceral innervation of target organs. It is the job of autonomic nerves to modulate, either up or down, the tone of the target organ, rather than to discretely stimulate it.
Denervation Supersensitivity: As a compensatory mechanism, a target loses autonomic innervation, it becomes hypersensitive to said neurotransmitter.

• Hypersensitivity due to increased synthesis of neuroreceptors.
• SYMPATHETIC LESIONS:
  • Preganglionic Lesion: Not so much hypersensitivity at target.
  • Postganglion Lesion: Pronounced Hypersensitivity because there is no longer a way for neurotransmitter reuptake to occur!!

Five Ways to Autonomically regulate End-Organ Activity:

• Antagonistic Effects on the same organ: Sympathetic and Parasympathetic have same effect.
  • Heart, Respiratory Passages
  • Urinary Bladder
  • Gut
• Antagonistic Effects through opposing organs: Sympathetic and Parasympathetic innervate different targets to achieve antagonistic effects.
  • Pupil (Pupil dilator and pupil constrictor)
  • Anal Sphincter
• Agonistic Effects on complementary organs: Salivary glands
• Agonistic Effects on the same target organ:
• Innervation by only one component: Lots of end organs
  • PARASYMPATHETIC ONLY: Lacrimal glands (CN VII), Nasopharyngeal Glands (CN VII), Tracheal / Bronchial Glands
  • SYMPATHETIC ONLY: Tarsal Muscles of eyelid. Loss of this function (drooping eyelids) is called Ptosis, a component of lost sympathetic innervation, or Horner's Syndrome.
    • Pilomotor smooth muscle
    • Sweat Glands: Excitatory sudomotor innervation
      • Eccrine Sweat Glands are cholinergic sympathetic. They are present all over and are responsible for thermoregulation.
      • Apocrine Glands = Sebaceous Sweat Glands. Mainly in axilla. They receive adrenergic innervation.
    • Spleen Capsule
    • Kidney stimulation for renin release

PENILE ERECTION:

• Parasympathetic vasodilation of penile arteries to yield erection.
• Sympathetic constriction of vas deferens and seminal vesicles for ejaculation.

SYMPATHETIC CIRCULATORY REFLEXES: Conform to the needs of fight or flight.

• Vasodilation of pathways leading to the heart and lungs.
• Vasoconstriction of pathways in the portal / GI system.