Physiology (Nuerohistology) Flashcards
Evolution of Human Brain
Brain has evoloved over millions of years
Rat brain has the same anotomical organizaion as humas - has the same basic structurs for functionb
Rat (Smallest) vs. Monkey (bigger - has more cells) vs. Human (biggest - 4X bigger than primates)
- Primates have aquired volume in CNS
- Human brain is well packed (compression of volume)
Cells found in CNS
CNS = contains nuerons + Glial cells
- Nuerons are associated with nueronal glial cells critical for CNS function)
Nueroglial cells + Blood vessles coest with nuerons - imprortant for maintaining the function of the brain
Features of neurons
Nuerons have many featires –> central to function of the brain
Have many subtypes of nuerons (different shapes and sizes depending on where they are located)
- Example - Cerebelum cortext cells are pyrimidal
Synapse
Basic communication methid for nuerons
Parts of neuron
- Cell body - doesn’t facilitate communcation - have dendrites + Axons
- Dendrites - improtant for synapse (connected to synapses) = faciliatate nueronal function
- Axon - Directs communicaion with other sturctures in CNS or outside the CNS
- Can be coated in mylin sheet or unmylinated
- Facilitates communcation with terminal ends + densdirtes
Neuron
The basic cell unite of the brain - facilitates the function of the CNS
- Neurons are organized in layers that form the cerebral cortext (grey matter)
- Other cells coexist with nuerons to maintain the function of the brain
Past throughts on glial cells vs. nuerons
Passed reserach only focused on nuerons but now reserach is begining to focus on nueronal glial cells
Function of nueronal glial cells
Nuerons need nueronal glial cells to function
Nueronal glial cells:
1. Oligiodentricyes - make myline
2. Astricytes - Asscoiated with nuerons or associated with blood vessles
Mylin
Facilitates conduction of electrical imuplues
- heavily mylinated = faster conduction
Blood vessels in brain
Blood vessels = important to birng blood into the brain - nueronal glial cells (Astrocytes) can assocuated with the Blood vessles to help bring blood in
Development of CNS during emryogenesis
Structires of teh CNS orginated in the nueronal plate –> Nueronal plate developes into the nueronal grrove –> Neuroinal groove developes into the nueronal tube –> Nueornla tube becomes the CNS
Nueoronal plate = derived from ectoderm –> Nuerona + nueornal glial cells originate in the nueronal tube
Division of nueronal tube
Nueronal tube is divided to different compartments
- Anterior (Forebrain) = gives rise to brain Gives rise to the brain hemispheres)
- Middle protion = gives rise to midbrain
- Lower down form middle pertion = Gives rise to hindbrain
- Posterior (bottom) = gives rise to the spinal cord
Sagital view - can see the forebrain in anterior –> the midbrain –> Spinal cord
Adult brain vs. brain during embryogensis
The adult brain mimics what we see in embryogensis
See forebrain becoming the brain
See middle protion becoming the midbrain
See posterior protino becoming the Spinal cord
Function of the brain + Spinal cord
All physiologycal function for motor + sensory + emotion
Spinal cord - highway for motor + sensory (distributes and captires information)
Frontal lobe function (overall)
Contains:
1. Pirmary motor cortext - volentary mucle movmet
2. premotor cortext/S.M.C - Planning and corrdination of movement (motor organization)
3. Frontal eye feld - volentary rapid eye movement
4. Prefrontal cortext - executive functions + behavior + personality
Frontal = largets portion of the brain
Frontal lobe - Motor cortext
Frontal lobe = contains the motor cortext = generates movment
- Cortical regions that generate movement = well organized (Ex. posterior region of motor = representative of all of the areas of the body - dfferent parts of the cortext control movment in differenr parts of the body
To get movment - cereral cortext needs to generate signal –> inputs signal to the primary motor cortext + pre-motor cortext
Occipital Love
Function - vision
part of the cerbal cortext taht processes vision infrmation form the retinal
Retina – Optic nerve –> Occipital lobe
Frontal Lobe + Executive function
Frontal lobe = important for organization + executive function
Example - when you wake up and getting ready for the day - need to use executive function –> EF is generated in the prefrontal cortext
- IF lose frontal lobe = lose executive function
Past treatment of mental disorder
20th century - treated mental disorders by taking out the frontal lobe –> pateints become calmer + destroy the ability to generate behavior and Executive function
Football players injury
Football players = damage frontal lobe = get behavioral probelms
Grey Matter Vs. White matter
Grey matter = organized in the cerbral cortext + in deep grey nuclei in the basal ganglia
Grey matter = has high density of nuerons + glial cells (“computers”)
White matter = High denisty of axons/mylination (“wiring”)
Different views of the brain
Left - MRI (high resolution imaging of the brain)
- See grey vs. white matter + different structres in the brain
Top Right - Coronal section –> See grey matter + Sulci + white matter + bridge between the right and left brain + see basal ganglion
- Bridge = Corpus colosum - axons that facilitate communication
Bottom Right - Lateral view (left = frontal lobe)
Spinal cord
Goes through the spine (spine = bony compartment that contains the spinal cord)
Spinal cord = highway
- Sends motor information form th ebrain to the limbs and takes sensory information from the organs to the brain
Trauma to neck/soine = disrupt communication = paralyzed
Two Paths in Spinal cord
- Acending (Sensory function) - Carry sensory ifnormation from organs to go to the brain
- Descending (Motor function) - uses the corteco spinal tract (used for motor)
Decending information in brain
Used for motot functions
To move -
1. Need to know ehere hand in in space (uses snesory nerves)
2. Need the forntal primary cortext to move hand (signal goe sto the primary motor cortext = move muscles) BUT you need to move sevral muscle at once
3. Signal goes ot the primary motor in white matter axons
4. Signal goes to the mibrain
5. Signal goes to the spinal cord
6. Spinal cord is connected to the spinal tract —> spinal tract packages the acins coordinating the motor information
What happens in the brainstem
In the brain stem - have pydrimidal deccustation
- IN brainstem a large percent of fibers that control right hand come from the left side of the brain (95% of fibers to move right hand come from left hemisphere)
BECAUSE in the brainste, the nerves cross the midline (have pyrimidal deccustation) –> control the right hand iwth left brain
Symptoms if have isse with decending information
See symptoms when examining motor control:
- Weakness (Ex. if have stroke and can’t move arm)
- Paralysis
- Stiffening (Spasticity) - diffculty moving limbs
- Cramps - Stress cortecospinal tract = get cramps
Bringing sensory information to the brain
Sensory = comes from the spinal cord –> spinal cord carriers information to the brain –> information goes to the thalumus –> thalumus gives the information to other area sin the brain
- Example - thalumus gives the information to the frontal lobe –> facilitates movement
- Example 2 - If hand touches something hot –> sensory infor goes to brain to withdraw the hand (motor cortext generates information to withdraw)
- Thalumus = deep white matter structure
Overall - Spinal cord –> gives sensor information to the motor cortext = genertaes movement
Sensory function issues
Symptoms:
1. Pain
2. Lack of snesation
3. Abnormal sensation
4. Lack of balance - if have numbness in feet or damage to the spinal cord = get issues with balance
What facilitates movment
Motor + sesory both facilitate movmemt
Nuerons in cerebral cortext
Nuerons in cerebral cortext to send and receive electrical signals = organized in layers
- Axons = in the white matter
Role of nueron
Generate electrical activity –> generates the electrocal activity using Nuerotransmitters
- Nuerons generate nuerotranmitters = generate eletrical function
- Nueron = uses elctrochemical acitivity
Have nuerotransmitters in cell body –> nuerotransmitters go to the axon –> nuerotrasnmittters go to the terminal –> complete function
Which cell in most important in the brain
NO one cell is most important in the brain (ALL of the cells are needed)
Center of the CNS
Center of the CNS = nuerons (people thought they were the most important but now we know that nuerons that do not have any other surroudning support cells cannot work)
What does nuerons need
Nuerons need:
1. Astrocytes
2. Glial cells
3. Mylinin (need ologiodentrites)
4. Atroglial cells - in close contact with nuerons + axons + blood vessels
5. Blood Bran Barrier - made up of endolthelium + perivascular macrophages
- BBB - has Blood vessles that connect blood with CNS
NO one cell is most important - if lose one element = get dysfunction
Where do cells in CNS come form
ALL cell come from the ectoderm EXCEPT microglual and macriphages
- Microglial cells + macrophages = come from mesoderms
Microglial + macrophages
Represenatves of the immune system in the CNS
Is the CNS immune privaleged
The CNS is NOT immune privaleged
Innate immunity = uses microglial + astroglia
BBB = important for immunity in the brain (cytokines and kemokines can get through)
- Modulates immune repinse using lymphocyte/monocyte traficking
Adaptive immunity = Specific T cell and antibody responses
What does the Nueron produce
Nueorn is an electrical and chemical factory
Cell body - produces nuerotransmitters –> Nurotransmitters go to the axon –> creates neurostimulation –> cauases a fucntion
Types of nuerotransmitters
- Excitatory nuerotransmitters (Ex. Glu) - Stimulates
- Inhibitory (GABA) - blocks function
CNS = based on electrical function –> have positive and negative signals
Brain development during emrbgenes + first year
During embryogensis first year get critical elements of organization:
- Nuronal + cortical organzation (get nuerons + glial cells)
- Synatic + Dendritic modeling (get the start of synapses/dendrtic organzation)
- Synaptic/dendritic organiaion = basis of nueronal function that will be the main function in the adult brain - Cortical networks develope
- Brain growth
Two things that occur during emrbyogensis + first year
Get orgnzation of nuerons + stimulation
IF during the babies first year there is not enough stimulation then the brain will have less organzation = need to stimulate babies
- Babies have deficit in synaptic acivity if there is no stimulation
Hypothesis for some nuerdevelopmental disorders = during utero and after = don’t get stimulation = don’t get factors that facillitate connectivity = get behavior abnomalities
Factors for organization of CNS
- Astrocytes - affects the movment and location of axons in teh cerbral cortext
- Cytokine + kemokines + immune cells facilitate function of Astrocytes
- Glial Cells - communcation with glial cells = improtant for organzation of CNS (uses the immune system for communication)
- Immune system
- If have disruption in utero = damage organzation (Ex. if mom gets virus while pregnant –> damage CNS organzation of baby)
Phase 1 of nueronal organzation
Phase 1 of nueronal organization = during utero + the first 2 years of life
What happens after age 2
After age 2 = Have phase 2 - Brain adaptation
- Nuerons + glial cells = generate nueronal connectivity
1st phase = Make stringer synaptic connections
2ns phase (Adaptation) = lower strength of sunaptic connections
- These connections are more suceotible to chnage
- Ex. learning in school
Example - if you stop learning math = you will lose the synaptic connections vs. primary language learned in the first two years won;y be lost because he synapses are stringer
First vs. second phase example
Languges - If learn a languge in the first two years of life –> languges will be impretented vs. If learn langauge in second phase (Adaptation) = you willl not have the same quality of imprinting as during the first phase
Reason why it is better to learn a language earler because later you will form wekaer synpases that cna be lost more easily
Synaptic plasticty Strength
Synaptic plasticty = string if aquired during development but not as strong during adaptation
Developmental vs. adaptive synaptic plasticity
Synaptic formation is lower in Adaptive synaptic plasticity = have lower quality of synapses after embryogensis
Adulthod = not as easy to maintain synapses = need to mainatin stimulation to maintain the synapses
Main modulaters of immune related pathological mechanisms
- Nuerovascular unit - uses glial cells (Astorcytes)
- Blood Brain Barrier
Astrocytes + Immune function
Astrocyes - important for CNS function)
1. Interact with the blood vesels = facilatte exchange with blood vessels + CNS
2. Have glial process/astrocytes tragets
Blood Brain Barrier
Modulatory Unit in the CNS
- Blood vessels = important for BBB
Have Edeothelal cells + macrophages - Opens the door to immune cells + cytokines + kemokines
Astrocyte Cell function
Interacts with Microglial –> important for nueral-neruogial interactions
- Form a network
Interacts with nuerons (Astroglial - nueronal interactions)
Axon guidence
Nuerotransmission
Blood brain barrier homoestasis
Microglial cells
Elements of the immune system
- Intercat with Blood vessles + Astrocytes + neurons
Diveristy of astroglial cells are important for
- Synaptogensis
- Synaptic plasticity
- Oligiodentricyte function
- BBB function
- Energetic support in CNS
What cells are used at the synapse
Synaspe = uses glial cells –> uses astrocytes
- Astrocytes = provide envrinment for synaptic structure
What is needed for electrochemical communication
In order to have electrochemical communication in pre and post synapse = need astrocytes to facilitate + ensure homoestatis of Nuertotrasnmitters
Glial cells = faciliatte trafficing of Nuerotransmitters + facilitates exchnage of turotrasnmitters + uptake of Nuerotransiteers + trageting of synapse to be deleted
Removing synapse
Form synapses –> if synapses stop doing function then you can remove synapses - Called “Synaptic modeling”
- Example - if you don’t use a languge = remove the synapses associated with the lanaguge
Process = uses mcroglial cells –> facilitate tagging of synapses to remove synaptic connectivity
How - Synapse is tagged by astorcytes with Clq fcators –> micorglia will will recognize these factors and phagocytoses and take away the synapse
Movment of NT at Synapse
Presynaptic nueron facilitates commincation by producing nuerotransmitters –> terminal of nueron puts the Nuerotrasnmitter into the cleft –> Nuerotrasnmitters go to the recetors on the post synaptic nueron
- Ex. NMDAR - glutamine receptor on post synaptic nueron
Perivascular astrocytes
Critical for Blood vessel function
lack expression of MHC Class II
Increase of perivascular processes
Express cytokiines + kemokines
Important in Glutamate metabolsim
Glial cells + Scarr tissue
Before reserachers though that glial cells facilitate scrar tissue formation
NOW - know that astroglil cells don’t make glial scar INSTEAD found that the glial cells are important in injury
- Found that glial cells make a glial factor and growth facors that facilitate in the recovery of axons = glial cells facilitate in regernatino NOT making fibrotic scar
- Overall - Astrocytes + glial scar contrubute to facilitation of axonal reconvery
NOW can use this information t get astroglial cells to comeplte CNS regernation in disease/injury
Santiago ramon y cajal
Studied histology of the CNS (pioneer in feild) – used photography and then the black and white pictre would pain the color by hand to show anatomy/histology
- Pioneer in the history of the immune system
His fellow (Rio-Hortega) - focus on drawing the other cells around the nuerons (drew the microglial cells)
- At the time the resercahers had a neurocentric philsophy (neuron is themain cell for excutive function) BUT the fellow discovered/reseracheed and found that many neurons were attached to microglal
- Had cajal calling the nueron the frist elements and Kortesy called microglia the 3rd elemements –> cajal got mad at the fellow –> fired the fellow
Microglia rediscovery
Microglia were rediscivered in the 21st century - found to be a critical element of the CNS
Old view - microglia = bad/inflamatory
New view = Microglia are importnat for metabolism + synaptic formation + trasnptopomic function + immunity
Where do micorglia orginate
Microglia = come form the mesoderm –> act as an imune cell in CS
Microglia = main mediators if innate immunity in CNS
- New reserach = maintaining microglia to regenerate nueron functions
Functions of microglia
- Survalence - sense injury to CNS
- Phagocytosis - synaptic plasticity = need microglia to remove the synapse when they are not needed
- Release factors for nueron communication
- Nuerogensis
- Synaptic remoeling
- Migration
- Inflamation
- BBB
Microglial = first to react at injury then the macrophages come to clean the area of nueronal injury
- Microglia = go to all structures in the CNS
Microglia development
Microglia = come from mesoderm
Duering embryogensis have wave of stem cells from the yolk sac –> stem cells populate the brain + the liver
- Stem cells in the brain –> gives rise to Microglial cells
- Stem cells in the liver –> give rise to Kupler cells
THEN have 2nd wave post emryogensis –> have hematohensis –> produce monocytes –> monocytes go to organs (macrophages go to difefrent organs)
- Monocytes traffic to the brain = become macorphages (macrophags mimic microglia cells)
Where do microglia go
Microglia go to all structures in the CNS
Macrophages - go to memgies + chorioid plexus + perivascular
Microglia interactions
Microglia is a dynamic cell in nuerical microglia interactiions
- Microglia = intercat with axons or blood vessels
What does Microglia drive
Microglia is the most important glial driver of synaptic plasticity in the CNS
- Microglia inertact with dendrites for phagocytosis of dendritic structure
- Microglia = recognize Cl1 = complete phagocytosis –> leads to synaptic homeostasis
Microglia astrocyte intercations
Microglia and astrocytes intercat for synaotic hooeotsasis –> needed for syanptic plasticity
Occurs in developing brain (have synapse elimniation) + less in mature brain (have stable connections)
- In neurodegentive disease = have excessive synatptic eliminarion
Perivascular macophages
Function as antigen presenting cells
Have receptirs for cytokines + kemokines
Produces cytokines + kemokines
Connected with Blood vessles in CNS
Derived from monocytes
Co-receptors for HIV (site of infection for HIV) –> facilitate infections
Oligiodendricytes
Oligiodendroglia = main cell in the CNS that produe myline
- Oligiodendricytes = critical for mylination
Heavily mylinated = faster conduction
CSF absorbption + production
Chorioid plecus = facilitates filtration of plasma
- Foun in ventrical system in CNS
- Facilitate the production of CSF
CSF
Surrounds the brain + spinal cord
- Facilitates metabolism function in brain
3000 white blood cells per mL of CSF
Have complete exchange of CSF 3 times/dat
Have constant influx/eflux of lymphocytes in and out of the CNS
Lymphatic system in CNS
Before - people thought that teh CNS did not have a lymphatic drainage system - means brain is not communicating with the lymphatic syste
Now - we know that the brain has lymphatic dranage –> means that metabolic products of the CNS can be drainedto the lympatic system using chanels going around the venous system in the brain
- Drainage = facilitates connection of barin with the lymphatic system
Brain + lymphatic system
Brain comminicates withe the lymphatic system –> tells immune cells that there is metabolic injury
- System = affects alzheimers disease
