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What neuro cells are derived from the neuroectoderm?
- CNS neurons
- Ependymal cells (inner lining of the ventricles that make CSF)
What neuro cells are derived form the neural crest?
What neuro cells are derived from the mesoderm?
- Microglia (like Macrophages; originate from Mesoderm)
What are neurons and their details?
- These compose the nervous system.
- These are permanent cells that do not divide in adulthood.
- Appear as large cells with prominent nucleoli.
What is Nissl substance/body and where is it located?
- These are the RER of the neurons where protein synthesis occurs.
- Found in the cell body and dendrites but not in the axons.
What is the function of astrocytes and what is the marker to ID them?
These are the "clean-up" cells of the CNS. They provide physical support, repair, K+ metabolism, remove excess NT and maintain the blood-brain barrier.
These are also responsible for reactive gliosis in response to injury.
Astrocyte marker = GFAP (marker for gliocytoma)
What is reactive gliosis and what cell is responsible for it?
This is similar to what fibroblasts do in the body and can create scar tissue. Astrocytes are responsible for this. *Remember they are the clean up cells of the the CNS.
What is the function of microglia and what are their distinguishing features?
- These are the CNS phagocytes. They are similar to macrophages and share the same mesodermal origin as them.
- These respond to tissure damage by differentiating into large phagocytic cells. **HIV-infected microglia fuse to form multinucleated giant cells in the CNS.
- Not discernible with Nissl stains, have small, irregular nuclei and relatively small amount of cytoplasm.
What is the function and details of oligodendroglia?
- These are the predominant type of glial cell in white matter and they mylinate multiple CNS axons (up to 30 each).
- In Nissl stain they look like small nuclei with dark chromatin and little cytoplasm.
- "Fried-egg" appearance on H&E staining.
- These get destroyed in Multiple Sclerosis.
What is the function and details of Schwann cells?
- Each one of these mylinates only 1 PNS axon.
- Promotes axonal regeneration and maintains axon integrity; each axon has multiple Schwann cells attached.
- Derived from the neural crest.
- These cells get destroyed in Guillain-Barre Syndrome.
- Clinical correlate: Acoustic neuroma is a type of Schwannoma typically located in the internal acoustic meatus (CN VIII).
Name the 4 main receptor types for sensory corpuscles.
- 1. Free nerve endings
- 2. Meissner's corpuscles
- 3. Pacinian corpuscles
- 4. Merkel's disks
What type of fibers are found with free nerve endings? Where are the locacted and what do they do?
- Free nerve endings use 2 different types of fibers:
- C fibers are slow and unmyelinated
- AS fibers are fast and myelinated
- These are found in all skin, epidermis and some viscera
- These are used for the detection of pain and temperature.
What type of fibers are found with Meissner's corpuscles? Where are they located and what do they do?
- These use large, myelinated fibers.
- Found in glabrous (hairless) skin
- Used for position sense, dynamic fine touch (ie: manipulation)
- These adapt quickly
What type of fibers are found with Pacinian corpuscles? Where are they located and what do they do?
- These use large, myelinated fibers
- Found in deep skin layers, ligaments and joints
- Used to sense vibration and pressure
What type of fibers are found in Merkel's disks? Where are they located and what do they do?
- These are large, myelinated fibers
- Found in the hair follicles
- Used to sense position, static touch (ie: shapes, texture)
- These adapt slowly
What are the peripheral nerve layers and details of each?
- 1. Endoneurium (endo=inner) - inner layer that invests a single nerve fiber. Location of inflammatory infiltrate in Guillian-Barre.
- 2. Perineurium (peri = around) - Permeability layer - surrounds a fascicle of nerve fibers. These must be rejoined for limb reattachement.
- 3. Epineurium (epi = outer) - dense CT that surrounds entire nerve (fasicles and blood vessels).
List the main NTs(7) and where they are made?
- 1. NE - made in locus ceruleus, solitary tract and reticular formation.
- 2. Dopamine - made in the ventral tegmentum and substantia nigra pars compacta.
- 3. 5-HT - made in the Raphe nucleus
- 4. ACh - made in the basal nucleus of Meynert
- 5. GABA - made in the nucleus accumbens (main inhibitory NT of the brain)
- 6. Glutamine - main excitatory NT of the brain
- 7. Glycine - main inhibitory NT of the spinal cord.
What diseases are caused by NE increase? decrease?
- Increase - anxiety, mainia, and use of cocaine and/or amphetamines.
- Decrease - depression
What diseases are caused by Dopamine increase? Decrease?
- Increase - schizophrenia
- Decrease - Parkinson's and depression
What diseases are caused by decrease in 5-HT?
anxiety and depression
What diseases are caused by ACh increase? Decrease?
- Increase - Parkinson's
- Decrease - Alzheimer's, Huntington's, REM sleep
What diseases are caused by a decrease in GABA?
Anxiety and Huntington's
What is associated with the locus ceruleus?
Stress and Panic
What is associated with the Nucleus accumbens and septal nucleus?
Reward center, pleasure, addiction and fear
What is the pathway for making 5-HT?
- Tryptophan -> (enzyme: typtophan hydroxylase*) -> 5-hydroxytryptamine -> 5-HT.
- * BH4 is taken to BH2 via tryptophan hydroxylase and BH2 is taken to BH4 by dihyrobiopterin reductase.
What is the GABA precursor and what do you need to make GABA?
Glutamate is the precursor and you must have Vitamin B6 to make GABA.
What is the reticular activating system composed of and what does it do?
- Composed of: 1. Reticular formation, 2. Locus ceruleus(NE), and Raphe nucleus(5-HT).
- Mediates consciousness and attentiveness b/c of increased NE and 5-HT.
- Lesion here results in coma.
What 3 structures form the blood brain barrier?
- 1. Tight junctions between non-fenestrated capillary endothelial cells
- 2. Basement membrane
- 3. Astrocyte processes
- **This is a very common theme throughout the body w/ endothelium, a BM and some type of parenchymal cell (ie: gas exchange/alveoli structure in lungs)
What other barriers in the body are similar to the BBB?
- 1. Blood-testes barrier
- 2. Maternal-fetal blood barrier of the placenta
What can destroy endothelial cell tight junctions of the BBB and what is the consequence?
Infarction can destroy the tight junctions resulting in vasogenic edema.
What substances can cross the BBB and how do they do it?
- 1. Glucose and amino acids cross slowly via carrier-mediated transport.
- 2. Non-polar/lipid soluble substances cross rapidly via diffussion. (A lot of anesthetics are lipid soluble and therefore have higher potency)
Name the areas of the brain w/o BBB (with fenestrated capillaries) and related effects.
- 1. Area postrema - causes vomiting after chemotherapy, OVLT-osmotic sensing
- 2. Neurosecretory products can enter the circulation such as with the neurohypophysis allowing for ADH release.
What are the main things that the hypothalamus controls?
- Remember TAN HATS:
- T - Thirst and water balance
- A - Adenohypophysis
- N - Neurohypophysis
- H - Hunger
- A - Autonomic Regulation
- T - Temperature Regulation
- S - Sexual urges
What are the input areas of the hypothalamus?
- OVLT - senses changes in osmolarity
- Area Postrema - responds to emetics
What are the areas/nuclei of the hypothalamus and what does each do?
- Supraoptic nucleus - makes ADH
- Paraventricular nucleus - makes oxytocin
- Lateral nucleus/area - hunger. Destruction = anorexia, failure to thrive (infants). Inhibitied by leptin. *If you zap your lateral nucleus, you shrink laterally.
- Ventromedial area/nucleus - satiety. Destruction (ie: craniopharyngioma) = hyperphagia. Stimulated by leptin. *If you zap your ventromedial nucleus you grow ventrally and medially.
- Anterior nucleus- Cool off, pArasympathetic. A/C = Anterior Cooling.
- Posterior nucleus - heating, sympathetic. *If you zap your posterior hypothalamus you become a Poikilotherm (cold blooded).
- Suprachiasmatic nucleus -circadian rhythm. * You need sleep to be charismatic(chiasmatic).
What does the posterior pituitary (neurohypophysis) do?
Receives hypothalamic axonal projections from the supraoptic (ADH) and paraventricular (oxytocin) nuclei.
**The Adenohypophysis is the anterior pituitary and releases TSH, GH, LH, FH, etc
What is the function of the thalamus? What are the main nuclei and their details(input, info, and destination?
- The thalamus is the major relay for ascending sensory information.
- Main nuclei include:
- 1. VPL (ventral postero-lateral) nucleus - this receives input from the spinothalamic and dorsal columns/medial lemniscus about pain, temperature, position and proprioception. Relays info to the primary somatosensory cortex.
- 2. VPM (ventral postero-medial) nucleus - this receives input from the trigeminal and gustatory pathway about face sensation and taste and relays it to the primary somatosensory cortex.
- 3. LGN (lateral geniculate) nucleus - this receives input from CN II about vision and relays it to the calcarine sulcus.
- 4. MGN (medial geniculate) nucleus - this receives input from the superior olive and inferior colliculus of the pons about hearing and relays to the auditory complex of the temporal lobe.
What structures make up the limbic system? Whare are the main fuctions of the limbic system?
- Includes/made up of - cingulate gyrus, hippocampus, fornix, mammillary bodies and septal nucleus.
- Responsible for the famous 5 F's - Feeding, Feeling, Fighting, Fleeing and Fucking.
- *This is a very primative system.
What is the main function of the cerebellum?
- It receives contralateral cortical input via the middle cerebellar peduncle and ipsilateral proprioceptive information via the inferior cerebellar peduncle. (input nerves = climbing and mossy fibers)
- Provides stimulatory feedback to contralateral cortex to modulate movement. (output nerves = purkinje fibers output to deep nuclei of cerebellum, which in turn output to cortex via the superior cerebellar peduncle)
What are the deep nuclei of the cerebellum?
Lateral to Medial -> Dentate, Emboliform, Globose, (Emboliform + Globose = Interposed nuclei) and Fastigial.
"Don't Eat Greasy Food"
What is the function of the lateral cerebellum?
- Functionally this is the cerebrocerebellum that communicates with the dentate deep nuclei and coordinates voluntary movement of the extremities.
- Lateral hemisphere = cerebrocerebellum which communicates to the cerebral cortex.
What is the function of the medial cerebellum?
- Functionally this is the spinocerebellum and is made of the vermis and peri-vermal regions. This communicates with the interposed (Enboliform and Globose) and Fastigal deep nuclei to coordinate balance, truncal coordination, ataxia, and the propensity to fall toward the injured (ipsilateral) side.
- Medial hemisphere = spinocerebellum which communicates to the spine.
What is the function of the basal ganglia?
- This is a system of multiple anatomic structures involved in either inhibiting or disinhibiting each other in different ways.
- This is important in voluntary movements and for making postural adjustements.
- Receives cortical input and provides negative feedback to the cortex to modulate movement.
What makes up the striatum of the basal ganglia? The lentiform?
- Striatum = putamen and caudate
- Lentiform = putamen and globus pallidus (internal and external)
What are all of the stuctures involved with the basal ganglia?
- Substantia nigra pars compacta (SNc) - normally this inhibits GPi and therefore stimulates movement. In Parkinson's this gets lesioned and therefore causes decreased movement.
- Substantia nigra pars reticulata (SNr)
- Globus pallidus externus (GPe) - facilitates movement
- Globus pallidus internus (GPi) - always inhibits movement when stimulated and always stimulates movement when inhibited
- Subthalamic nucleus (STN) - increases GPi therefore it always inhibits
- Dopamine D1 receptor (excitatory)
- Dopamine D2 receptor (inhibitory)
How does the Direct/excitatory pathway work? How is it affected by Parkinson's disease?
- SNc's dopamine binds D1 receptors to stimulate the excitatory path and increase motion.
- Loss of dopamine in Parkinson's inhibits the excitatory pathway b/c there is nothing to bind/activate the D1 receptors; this results in loss of motion.
How does the indirect/inhibitory pathway work? How is it affected by Parkinson's disease?
- SNc's dopamine binds D2 receptors in the inhibitory pathway which inhibits the inhibitory pathway and increases motion.
- Loss of dopamine in Parkinson's excites/disinhibits the inhibitory pathway allowing it to cause inhibition and decreased motion.
What are the 2 most common sites of HTN hemorrhage?
Basal ganglia and the thalamus.
Where does the basal ganglia arterial supply come from?
Lenticulostriate arteries supply the basal ganglia; they come from the MCA
What is the function of the thalamus (VA/VL) and other nuclei?
- Stimulates the cerebral cortex
- Stimulates the striatum
- Gets inhibited by the globus pallidus internus and the SNr.
What is a surgical way to treat Parkinson's disease(w/ movement inhibition)?
- Lesion the subthalamic nucleus b/c it will decrease movement inhibition/ increase movement stimulation.
- This can be done surgically or with Deep Brain Stimulation(makes it non-functional)
What are the diseases of the basal ganglia?
What are the 2 main types of disease of the basal ganglia?
- Excess movement inhibition (ex: Parkinson's)
- Excess movement excitation (ex: Hemiballismus)
What is Parkinson's disease? What are the clinical S/S?
- Parkinson's disease is a degenerative disorder of the CNS associated with Lewy bodies (alpha-synuclein intracellular inclusions) and depigmentation of the substantia nigra pars compacta (loss of domaminergic neurons).
- A decrease in pigmentation shows a decrease in DOPA and therefore a decrease in dopamine which is made from DOPA. This is seen to some degree in 1% of all people >60
- Clincial S/S - TRAP - Tremor (at rest/pill rolling), Rigidity (cogwheel), Akinesia, and Postural instability.
What are the divisions/areas of the cerebral cortex and the functions associated with each?
- Frontal - principal motor area, premotor area, frontal eye fields and motor speech area (Broca's area) in dominant hemisphere
- Parietal - principal sensory areas; seperated from the frontal lobe by the central sulcus
- Occipital - primary visual cortex
- Temporal - primary auditory cortex(Herschl's gyrus), associative auditory cortex(Wernicke's area in dominant hemisphere)
What is the function of the frontal lobe; what makes it unique?
- This is what makes us human.
- Allows for planning, inhibition, concentration, orientation, language, abstraction, judgement, motor regulation and mood.
- Lesion to this area can cause lack of social judgement and major personality changes. Remember Phineaus Cage.
What is the homonculus?
- This is a topographical representation of sensory and motor areas of the cerebral cortex.
- Used to localize lesions leading to specific defects
- There is a motor and sensory homonculus on either side of the central sulcus.
What is supplied by the Anterior cerebral artery? The Middle cerebral artery? The Posterior cerebral artery?
- ACA - anteromedial surface (leg/foot)
- MCA - lateral surface (mouth/hand)
- PCA - posterior and inferior surfaces (visual)
What arteries make up the Circle of Willis?
- Anterior cerebral
- Anterior communicating
- Middle cerebral
- Internal carotid
- Posterior communicating
- Posterior cerebral
- Anterior inferior communicating
- Posterior inferior communicating
- Anterior spinal
What are the dural venous sinuses?
- Venous sinuses that run in the dura mater where its meningeal and periosteal layers seperate.
- Cerebral veins --> venous sinuses --> internal jugular vein
- Venous sinus path: Superior sagittal sinus (main location of CSF return via arachnoid granulations) --> transverse sinus --> sigmoid sinus (becomes jugular vein once it crosses the jugualr foramen)
- Also have cavernous sinus, inferior sagittal sinus, straight sinus, occipital sinus and sphenoparietal sinus.
What is the pathway of the CSF through the ventricular system assuming the lateral ventricle is the start point?
Choroid plexus makes CSF --> lateral ventricle --> (goes through the Foramen of Monro) --> 3rd ventricle --> (goes through the cerebral aquaduct) --> 4th ventricle --> ( splits and goes through the Foremen of Magendie medially and the Foramen of Luschka laterally) --> subarachnoid space --> superior sagittal sinus --> transverse sinus --> sigmoid sinus --> becomes jugular vein.
How many spinal nerves are there? Where do they exit?
- There are 31 total spinal nerves; 8 cervical, 12 thoracic, 5 lumbar, 5 saccral and 1 coccygeal.
- Nerves C1-C7 exit via intravertebral foramina above the corresponding vertebra; all other nerves exit below.
What is vertebral disk herniation and where does it most commonly occur?
- Disk herniation is when the nucleus pulposus herniates through the annulus fibrosus.
- Most commonly occurs between L5 - S1
What level does the spinal cord extend down to in adults? Where is a lumbar puncture usually performed in adults? What structure is used to find L4?
- SC extends to the lower border of L1-L2 in adults with the subarachnoid space extending to the lower border of S2.
- Lumbar puncture is usually performed btwn L3-L4 or L4-L5 interspaces at the cauda equina.
- The anterior iliac crest is used to find the level of L4.
What makes up the dorsal colums and what type of information do they carry?
- Dorsal columns carry information about pressure, vibration, touch and proprioception.
- Made up of the Fasciculus Cuneatus that serves the upper body and extremities, and the Fasiculus Gracilis that serves the lower body and extremities (remember graceful ballerina on her toes)
- *Dorsal column is organized as we are with arms on the outside and legs on the inside/medial.
What information is carried in the lateral corticospinal tract?
What information is carried in the spinothalamic tract?
Pain and Temperature
What is the 1st order neuron of the dorsal column, what is its path and where does it synapse/where is the first synapse? Describe the 2nd order neuron and 2nd synapse and the location of the 3rd order neuron.
- 1st order neuron is in the sensory nerve ending --> cell body in the dorsal root ganglia --> enters the spinal cord, ascends ipsilaterally in the dorsal column --> has 1st synapse on the ipsilateral nucleus cuneatus or gracilis in the medulla.
- The 2nd order neuron then decussates in the medulla --> ascends contralaterally in the medial lemniscus --> has 2nd synapse on the VPL of the thalamus.
- 3rd order neuron is in the sensory cortex
When do ascending tracts synapse?
Before they cross.
What is the 1st order neuron of the spinothalamic tract and where is the 1st synapse? Describe the 2nd order neuron and the 2nd synapse. Where is the 3rd order neuron?
- 1st order neuron is in the sensory nerve ending (A-delta and C fibers) --> cell body in the dorsal root ganglia --> enters spinal cord --> 1st synapse in the ipsilateral gray matter of the spinal cord.
- The 2nd order neuron decussates at the anterior white commisure -->ascends contralaterally --> 2nd synapse in the VPL of the thalamus
- The 3rd order neuron goes to the sensory cortex
What is the 1st order neuron of the lateral corticospinal tract and where is the 1st synapse? Describe the 2nd order neuron and the 2nd synapse.
- 1st order neuron is an UMN: cell body is in the primary motor cortex --> descends ipsilaterally through the internal capsule --> decussates at the caudal medulla (pyramidal decussation) --> descends contralaterally --> 1st synapse in the cell body of the anterior horn of the spinal cord.
- 2nd order neuron is a LMN: leaves the spinal cord --> 2nd synapse at the neuromuscular junction.
What are the clinically useful landmark dermatomes?
- C2- posterior half of a "skull cap"
- C3 - high turtleneck shirt
- C4 - low collar shirt
- T4 - at the nipple (T4 at the Teat Pore)
- T7 - xiphoid process
- T10 - at umbilicus; useful for early appendicitis referred pain (T10 at the belly butTEN)
- L1 - inguinal ligament (L1 is IL-inguinal ligament)
- L4 - includes the kneecaps (Down on L4s(all fours))
- S2,S3,S4 - erection and sensation of penile and anal zones (S2,S3,S4 keep the penis off the floor)
What are the clinical reflexes?
- Biceps = C5 nerve root
- Triceps = C7 nerve root
- Patella = L4 nerve root (down on L4's(all 4's))
- Achilles = S1 nerve root
- Babinski = dorsiflexion of the big toe and fanning of other toes; sign of an UMN lesion but normal during 1st year of life
- ***Reflexes count up in order: S1, S2, L3,L4, C5,C6, C7,C8
What are the primitive reflexes? When are they seen?
- Moro Reflex - (the "Oh Shit" reflex)- abduct/extend limbs when startled and then draw together.
- Rooting Reflex - movement of head toward one side if cheek or mouth is stroked (nipple seeking)
- Sucking Reflex - sucking response when roof of mouth is touched
- Palmar and Plantar reflexes - curling of fingers/toes if palms/soles are stroked
- Babinski Reflex - dorsiflexion of large toe and fanning of other toes with plantar stimulation.
- ***These are seen in the first year of life then normally disappear. However, they may reemerge following a frontal lobe lesion or basically any UMN lesion.
What are the purely sensory cranial nerves?
- CN I - Olfactory
- CN II - Optic
- CN VIII - Vestibulocochlear
What are the purely motor cranial nerves?
- CN III - Occulomotor
- CN IV - Trochlear
- CN VI - Abducens
- CN XI - Accessory
- CN XII - Hypoglossal
Which cranial nerves are both motor and sensory?
- CN V - Trigeminal (motor - muscles of mastication, sensory - facial sensation)
- CN VII - Facial (motor - expresssion, sensory - taste from anterior 2/3 of tongue, lacrimation, salivation)
- CN IX - Glossopharyngeal (motor - swallowing, stylopharyngeus; sensory - taste from posterior 1/3 of tongue, salivation)
- CN X - Vagus (motor - swallowing, palate elevation, talking; sensory - taste from epiglottic region)
What CNs have nuclei in the midbrain?
CN III and IV
What CNs have nuclei in the Pons?
CN V, VI, VII, and VIII
What CNs have nuclei in the Medulla?
CN IX, X, XI and XII
What are the cranial nerve reflexes? State the afferents and efferents involved in each.
- Corneal reflex: Afferent - V1 ophthalamic (nasociliary branch: levator palpebrae). Efferent - VII (temporal branch: orbicularis oculi)
- Lacrimation reflex: Afferent - V1 (loss of reflex does not preclude emotional tears); Efferent - VII
- Jaw Jerk reflex: Afferent - V3 (sensory - muscle spindle form masseter); Efferent - V3 (motor - masseter)
- Pupillary reflex: Affernt - II. Efferent - III
- Gag Reflex: Afferent - IX, Efferent - IX and X
What are the vagal nuclei? What are their functions/actions and what CNs are invovled (if any)?
- Nucleus Soltarius - visceral sensory information (eg: taste, baroreceptors, gut distention). Includes CN VII, IX and X.
- Nucleus Ambiguous - Motor innervation of the pharynx, larynx, and upper esophagus (eg: swallowing, palate elevation). Includes CN IX, X, and XI.
- Dorsal Motor Nucleus - Sends autonomic (parasympathetic) fibers to the heart, lungs and upper GI. No CN involvement. Name is a misnomer b/c this is not motor.
What is the cavernous sinus? What important structures pass through it?
- Cavernous sinus is a collection of venous sinuses on either side of the pituitary. Blood from eye and superficial cortex --> cavernous sinus --> internal jugular vein.
- CN III, IV, V1, V2 and VI plus postganglionic sympathetic fibers en route to the orbit all pass through here. Cavernous portion of the internal carotid artery is here too.
What are the muscles of mastication? Which ones open the jaw and which ones close it? What is the innervation for each muscle?
- 3 muscles close the jaw: Masseter, teMporalis, Medial pterygoind. (M's munch)
- 1 muscle opens the jaw: Lateral pterygoid. (Lateral lowers)
- All 4 muscles are innervated by CN V3.
What is the pathway of the aqueous humor?
Ciliary process (Beta) produces aqueous humor --> goes through the posterior chamber --> Anterior chamber --> trabecular meshwork (absorbs aqueous humor) --> canal of Schlemm(collects aqueous humor from trabecular meshwork)
What are the extra-ocular muscles, their innervation and direction the move the eye.
- Inferior oblique - CN III - moves eye up and in
- Inferior rectus - CN III - moves eye down and out
- Medial rectus - CN III - moves eye medially
- Superior rectus - CN III - moves eye up and out
- Superior oblique - CN IV - moves eye down and in
- Lateral rectus - CN VI - moves eye laterally
How is pupillary constriction (miosis) controlled?
Pupillary sphincter muscle (aka circular muscle) controls this via parasympathetic stimulation from the CN III E-W nucleus that goes to ciliary ganglion.
How is pupillary dilation (myDriasis) controlled?
Radial muscle (aka pupillary dilator muscle) controls this via sypmpathetic stimulation from T1 preganglionic sympathetics --> superior cervical ganglion --> postganglionic sympathetic --> long ciliary nerve.
What is the pupillary light reflex? What is the complete pathway?
- Light in either retina will cause both eyes to contract bilaterally (consensual reflex).
- Light --> cells of retina --> optic tract --> optic nerve --> pretectal nucleus --> bilateral E-W nucleus --> preganglionic PS fibers in CN III(both eyes) --> ciliary ganglion --> postganglionic PS fibers --> pupillary sphincter of iris --> pupillary constriction(miosis) of both eyes.