NEU 490 Quiz 2 Ast Flashcards
Astrocytes Shape and Location?
Astrocytes Roles?
Local communication?
Astrocytes Abundant? Compare to neurons?
% total brain volume?
% brain glial population?
adapt size and shape to form a BLANK?
Overlap?
Star Shaped glial in the brain and spinal cord
Many roles: biochemical control of endothelial cells to help form BBB, provide nutrients to nervous tissue, maintenance to extracellular ion balance, regulation of cerebral blood flow, role in uptake of NT (glutamate), repair scarring in the brain and spinal cord flowing infections and injuries
Seen as local communication elements of the brain, can generate regulatory signals, bridge structures and create networks
most abundant macroglia (outnumber neurons 5:1)
constitute 20-50% of total brain volume
40-50% of brain glial population - 50% of glial cells are astrocytes
adapt size and shape to form a tridimensional net throughout CNS
Relatively little overlap of processes but can connect through gap junctions for intracellular Ca
Old Theory vs New Theory
Glial Fibrillary Acid Protein (GFAP)?
Old theory: homogeneous population of non- excitable cells (considered support cells but with RNA seq, ICH, and Ca imaging view has changed that they are diverse population of cells and have brain area and disease specific functions)
Homogeneous means something is uniform in nature or made up of parts that are the same or very similar, while heterogeneous means something is made up of parts that are different or unalike.
New theory: dynamic heterogeneous population of cells (don’t send AP but are excitable and send intracellular and intercellular Ca waves between diff astrocytes through long distances on response to stimulation - release glial transmitters that they make or take up)
Glial Fibrillary Acid Protein (GFAP): common astrocyte marker but the density of expression of various markers differs across astrocyte subtypes
Three Identifiable Types:
Divided according to?
Protoplasmic?
Fibrous?
Radial?
Change in shape can have reduction in number of fine processes and increase in size of soma and thickness — Divided according to morphological characteristics, location, and cellular markers
Protoplasmic: (sheet-like; gray matter) near neuronal cell bodies and synapses
Fibrous: (stellate; white matter) near myelin
Radial: (thin unbranched; white matter, progenitor cells) important for development and can tune into neurons and be guidance for neurons but different in adult brain - not considered a true astrocyte but have similar functions
Protoplasmic Astrocytes
Morphology?
Gray matter enfold?
Roles in synapses?
Role in BBB?
Take up what?
What allows for propagation of Ca?
Morphology: Highly branched and bushy processes - Stellate or Star-shaped
Gray matter(cell bodies,synapses) astrocytes that enfold cell bodies and processes - play role at synapse
Play a role in synaptic function - glutamate clearance, buffering of ion conception, modulation of functions, and regulation of blood flow in response to synaptic activities (send blood flow to active areas of the brain that’s why FMRI), formation and elimination of synapses, microglia actually phagocytes the synapses, astrocytes will tag this is a not used synapse get rid of it
Play a role in the BBB - bring blood flow
Non-overlapping domains and mutually exclusive domain - within the domain if one single astrocyte are 140,000s synapses so coordinate synaptic activity IN to blood flow
Take up glutamate bc in contact with NT
Gap junctions allow for propagation of intracellular Ca to allow for communication
One protoplasmic astrocyte can come into contact with up to BLANK synapses
140,000
Which of the following are true regarding protoplasmic astrocytes?
Gray matter
large stores of glycogen
come into contact with synapses
BBB formation
regulating blood flow
high expression of glutamate transporters
Fibrous Astrocytes
Derived from same progenitors as?
White matter?
Run between?
make contact ?
regulate?
Affect maintenance of what two things?
Frequently form?
Derived from same progenitors as protoplasmic
White matter(myelin) astrocytes - scattered in of spinal cord and brain
In the CNS matter in major routes
Run between myelinated fibers
make contact with Nodes of Ranvier
regulate environment around axons and interaction with oligodendrocytes, vascular, and microglia and regulate network activity by contact with axons - increase in Ca waves intracellular in response to APs being sent and induce release of ATP which is important for transmitter for activation of microglia and neurons and astrocytes
Affect maintenance of oligodendrocytes and effect myelin by having platelet derived growth factor alpha PDGFA which mediate survival of OPC and miotic expand of OPC
Frequently form endfeet with capillaries - BBB creation and maintenance - bring blood flow
Which of the following are true regarding fibrous astrocytes?
Located in white matter, lower expression of glutamate transporters, contact with nodes of ranvier, BBB formation, relegating blood flow, lower expression of connexions; less gap junction coupling
BLANK astrocytes release BLANK to increase oligodendrocyte progenitor cell numbers during development and influence myelination
Fibrous, (PDGFA) platelet derived growth factor alpha
Radial Glia
Biochemically and functionally distinct non?
location?
guiding what?
branched?
Progenitor cells?
Two types?
Biochemically and functionally distinct non neuronal cell class that radically spans entire width of cerebral wall from ventricular cavity(ventricles) to pial surface, ubiquitous throughout developing brain and guidance movement of neurons
Glial cells with long unbranched processes
Progenitor cells, stays in adult brain in discrete locations - act as progenitor cells for development so can turn into neurons
Müller Cells of the Retina: elongated throughout the thickness of the retina
AND
Bergmann glia: Golgi epithelial cells of the cerebellum–extend through the molecular layer to the cerebral cortex
Müller Cells of the Retina: ?
Major or minor?
Functions?
Regulate?
Optical?
Protection?
Müller Cells of the Retina: elongated throughout the thickness of the retina
Major type of glia in retina
Functions: Homeostasis and metabolic support of retinal neurons and mediate transport of ions ECF composition, trophic support, oxidative support for photoreceptors, and tights of blood retinal barrier
Regulation in synaptic activity
Optical fibers able to guide light through retina and enhance signal to noise ratio
Provide protection incase of mechanical trauma
Bergmann glia: ?
Closely associated with?
Normal?
Migrate who?
Prune?
After injury?
Bergmann glia: Golgi epithelial cells of the cerebellum–extend through the molecular layer to the cerebral cortex
Closely associated with perkingy neurons in cerebellum
Specialized astrocytes
Migration of granular cells
Synaptic pruning
Proliferative after injury called gelosis
Protoplasmic VS Fibrous Astrocytes
Protoplasmic: neurons many contacts at synapses, glutamate exposure high and glutamate clearance high with high GLT-1 expression which is the glutamate transporter that takes up glutamate, high glycogen content to convert to glucose, gap junction coupling has intense coupling connexins 43 and 30
Fibrous: neurons contact only at node, glutamate exposure low and glutamate clearance low with low GLT-1 expression, low glycogen content, gap junction coupling has less coupling mainly connexin 43
Astrocytes Functions: Neurogenesis Early Development (4) VS Adult (5)
Neurogenesis Early Development
- Scaffolding/Neuronal Migration: Directing neuron migration via direct cell contact (scaffolding), Directing neuron migration via chemo attraction and repulsion
- Neuronal Survival: Secretion of growth (survival) factors
- Synaptogenesis: Control the # of synapses formed, Maintain neuronal synapses
- Formation of the blood brain barrier (BBB)
Adult
- Energy Metabolism
- Maintenance of Neuronal Homeostasis
- Maintenance of Neuronal Activity/Plasticity
- Neuron-to-glia, Glia-to-glia and Glia-to-neuron signaling
- Regulation of Blood Flow
Scaffold - Development
Temporary structure used when building
Guides worker from bottom to top
Directing neuron migration via direct cell contact
Neurons move along processes of radial glial cells - scaffold to help new travel by Leading process does not pull the neuron along.
Lamellipodia and filopodia extend and retract.
The neuron moves by release and reformation of the adhesion beneath the cell soma
Antibodies against glial surface molecules block migration
Guiding neuronal cell migration - Brain development
Glia are neuronal stem cells: act as? use what to guide neurons? Apical RG VS Basal RGs?
New neurons? travel for? stem cells? zone?
Neurons continuously exploring environment for?
lamellipodia and filopodia?
Parcaine signaling?
Contact dependent signaling requires?
Chemoattraction?
Chemorepulsion?
Glia are neuronal stem cells: Radial glia act as stem cells divide into neurons or neuronal progenitor cells and then act as as scaffold to help new travel
Have polarity that guides neurons from one surface to another by intracellular Ca - basal region radial glial end up guiding neurons to migrate in right direction
Apical RGs cell body in vertical zone and apical process in ventral and basal process to reach pia
Basal RGs cell bodies in cortical zone wall which is outer and limits to vertical
Scaffold for new neurons so organization location and positions of the neural network - development travel long distances in expanding tissue so radial glial(stem cells) in ventricular zone turn into neurons and travel along other radial glial processes toward cortex
Neurons continuously exploring environment search for guidance cues so have proper connections made and neuronal network
Growth cones for major motile structure in axon guidance and found at neurite tips (new process from a neuron) made up of lamellipodia and filopodia which provided exploratory motion this is can attract or repel molecules
Parcaine signaling signals released in extracellular place like soluble factors and factors are highest where it is released so highest concentration diffuses out and signals are picked up by growth cones and will be repel or attract
Contact dependent signaling requires cells to be in direct membrane to membrane contact so attracted to signaling molecule
Chemoattraction: Netrin-1 release induced attraction and tuning of growth cone to signal
Chemorepulsion: Sema3A molecule repulsive factor
Which cell type guides neurons to their destination AND is the progenitor for newly born neurons?
Radial Glia
Radial glia cells have polarity. The BLANK end is located near the ventricular zone, the BLANK end is located near the pial surface.
Apical, Basal
Astrocyte Survival/Growth Factors - Development
Astrocytes are required for - Survival?
Growth Factors Names?
Do neurons also express these growth factors?
Growth factors are involved in regulation of?
Survival: the more processes the more complex and without a process a neuron cannot communicate. Astrocytes are required for the initiation for development of neurons and the maintenance of neuronal survival and complexity
Nerve Growth Factor (NGF)
Brain Derived Neurotrophic Factor (growth factor) (BDNF)
Neurotrophin 3 (NT-3)
Neurotrophin 4 (NT-4)
Glia Derived Neurotrophic Factor (GDNF) - has specific receptors
Neurons also express growth factors NGF, BDNF, NT-3, NT-4 BUT astrocyte have 2x the expression of them
Growth factors are involved in regulation of growth factors, maintenance, proliferation, survival of neurons but when missing neurons undergo apoptosis. Disruption of growth factors is associated with neurological disorders.
Synaptogenesis - Factors Development
Synapse is essential for?
3 stages?
During development neurons born before astrocytes, can see?
axodendritic?
axosomatic?
axoaxonic?
Establishment of correct number and types of synapse is essential for formation of neural circuits and brian processing
3 stages:
- Immature synapses form between axons and dendrites
- Synapse undergo maturation - converting silent synapse (no electrical conduction needs to mature)
- Excess synapses need to be ruined inorder to refine the circuit
During development neurons born before astrocytes, can see large jump in number and completely of synapses when astrocytes show up
axodendritic: (axon communicating with dendrite) synapse
axosomatic: (synapse directly on soma of post) communicating synapse
axoaxonic: (axon synapse on axon - for interneuron/sculpt activity) synapse
Formation of synapses between neurons in the nervous system - Development
Tripartite Synapse?
Astrocyte interact with?
Can respond to and regulate what activity?
Communication with both?
Thrombospondin?
Hevin promotes?
ECM(astrocytes release) =?
Contributions of astrocytes to synapse?
Tripartite Synapse: refers to the functional integration and physical proximity of: The presynaptic membrane, Postsynaptic membrane, and their intimate association with surrounding glia.
Astrocyte processes are in close neighborhood of the pre- and postsynaptic elements and interact with these functional elements in various functional pathways.
Can respond to synaptic activity and regulate activity
Communication with both pre and post synapse
Thrombospondin are released at synapse that interact with neuroligand and can affect VG calcium channels in order to induce excitatory synapse sculpting
Hevin promotes formation of excitatory synapses and they bind to integrin
ECM(astrocytes release) = extracellular matrix helps to stabilize synapses and ensure synapses are properly formed and can have communion with pre and post
Contributions of astrocytes to synapse formation and maturation — Potential functions of the perisynaptic extracellular matrix
Formation of synapses between neurons in the nervous system - Development - Contributions of astrocytes to synapse formation and maturation/Astrocytes control the #of synapses formed Participate in Synaptic Stability and Maintenance
Role of soluble factors released from astrocytes?
Help form perineuronal nets which are?
Neurons and glial cells important direct contact?
synaptic activity compared to With and without Astrocytes?
Dendritic Spine Role?
Role of soluble factors released from astrocytes - Help form perineuronal nets which are complex assemblies of ECM components and can help regulate the sprouting and pruning of synapses in the developing brain which helps for making synapses but in adult brain it is form plasticity
Neurons and glial cells were cultured without direct contact to each other to investigate effects of soluble astroglial-derived components on synaptogenesis for 3d (B), 6d (C) and 13d (D). Expression of the presynaptic protein Bassoon and the postsynaptic protein ProSAP1/Shank2 after 13d in culture.
Spontaneous synaptic activity in purified retinal ganglion cells (RGCs) that were cultured for 5 d in defined medium in the absence (left) or presence (right) of collicular glia. 5 days in culture –retinal ganglion cells
With Astrocytes - see mini excitatory postsynaptic potentials (MEEPPS) release of one vesicle of NT called quantal release so electorally active synapse
Without Astrocytes - silent synapse
Dendritic spine: protrusions that help form individual synapse
There are different scaffolding proteins required for proper synapse formation, and astrocytes help ensure proper expression of these proteins.
What is PSD-95?
What is gephyrin?
Do their expression patterns differ?
What are there some potential diseases or disease processes caused by dysfunction in either protein?
What is PSD-95? Scaffolding protein at excretory which uses NMDAR and AMPAR receptor
What is gephyrin? Inhibitory synapses which uses GABA and glycine
Do their expression patterns differ? Different for inhibitory vs excitatory
What are there some potential diseases or disease processes caused by dysfunction in either protein? Schizophrenia mostly PSD-95, Stih motor disorder for gephyrin
Which of the following things might happen if soluble factors released from astrocytes are blocked, and can therefore not act on neurons? Select all that apply:
A. Reduction of neuronal survival - growth factors
B. Reduced creation of new neurons radioglia are the progenitors
C. Reduced synapse size and number
D. Reduced microglial interaction with neurons
E. Absent or reduced electrical activity in neurons
F. Reduced migration of neurons to proper destination during development - chemoattraction and chemorepulsion
G. Reduced migration of neurons on radial glia processes, inability to attach - requires direct contact
A, C, E, F
Adult - Energy Metabolism - Metabolic support
lactate shuttle hypothesis?
role of capilrors and glucose?
Within astrocytes role of glucose?
Lactate transported to neurons as energy source: Transported from glia by? AND Transported to neurons?
Within neurons?
lactate shuttle hypothesis (a way for astrocytes to provide energetic support for neurons)
Capilrors release glucose and is trafficted into astrocytes by transporters GLUT 1 and glucose converted in astrocyte to glycolysis into pyruvate then lactate - Glucose is transported into astrocytes - take more glucose than neurons
Within astrocytes: glucose stored as glycogen,
glucose converted to lactate by glycolysis - in astrocytes this can occur in aerobic or anaerobic conditions
Lactate transported to neurons as energy source: Transported from glia by monocarboxylate transporter 1 (MCT1) AND Transported to neurons by MCT2
Within neurons, ATP produced by oxidative phosphorylation - lactate in neurons turned into ATP
Adult - Maintenance of Neuronal Homeostasis
Maintenance of microenvironment of the brain in ECF which is what rich and poor?
Regulation of extracellular K+
1st way
2nd way
Maintenance of microenvironment of the brain in ECF which is Na rich and K poor so excess K changes concentration gradient so more K stays in cell so hyperpolarize
Regulation of extracellular K+:
1 way: K+ uptake - through transports and K channels that balance K influx by either uptaking Cl or heance Na leave via active pump
- passive K+ + Cl- uptake
- Active transport by Na+ pump
2 way: K+ transfer by current flow - drive to leave but poor environment
- K+ spatial buffering
- Astrocytes connected via gap junctions
- Astrocytes is highly and selectively permeable to K
Adult Maintenance of Neuronal Homeostasis - Glutamate transport into astrocytes
Too much glutamate lends to?
After glutamate release only 20% is and 80% is?
Glutamate transport expressed by structures are EAAT 1&2 which is a? EAAT is trafficked dependent when?
Breaking down to glutamine?
Breaking down to alpha- ketoglutarate?
Which breaking down depends on the concentration of?
Too much glutamate lends to excitotoxic effects on neurons
After glutamate release only 20% is blinding to post or transport back into pre so 80% is taken up by astrocytes
Glutamate transport expressed by structures are EAAT 1&2 which is a perisynaptic process so right next to or close to synapse
EAAT is trafficked dependent when bring in glutamate and then excess sodium is trafficked out using the sodium potassium pump
Breaking down to glutamine: Glutamate to glutamine then either release glutamine or make glutamate and make GBAB
Breaking down to alpha- ketoglutarate: Glutamate breakdown via oxidative phosphorylation to alpha- ketoglutarate to make ATP
Which breaking down depends on the concentration of glutamine in extracellular space. Less than 0.2mm then glutamine and if more than alpha
Adult - Maintenance of Neuronal Activity/Plasticity
* Neuron-to-glia, Glia-to-glia and Glia-to-neuron signaling
Neuron to glia signaling:
Light stimulation of retina:
- Light-evoked Ca2+ increases in?
- Neuron to glia signaling mediated by?
Visual stimulation of the ferret in vivo:
- Ca2+ imaging?
- Astrocyte Ca2+ responses mediated?
- Astrocyte responses have selective?
Glial cell release of transmitters:
Gliotransmitters?
Release mechanisms: Ca2+-dependent release, Vesicular release via exocytosis, Release via anion channels, hemichannels?
Neuron to glia signaling:
Light stimulation of the retina
- Light-evoked Ca2+ increases in retinal glial (Muller) cells
- Neuron to glia signaling mediated by ATP release from neurons - astrocytes use intracellular calcium waves when activated to see if an astrocyte is activated so instead of AP to see look at calcium fluxes
Visual stimulation of the ferret in vivo
- Ca2+ imaging of neurons and astrocytes in visual cortex
- Astrocyte Ca2+ responses mediated by glutamate release from neurons
- Astrocyte responses have selective receptive field properties (similar to neighboring neurons) - V1 neurons are releasing glutamate bc mapped retinotopically and astrocytes react to glutamate release this they are also retinotopically mapped bc astrocytes do not move
Glial cell release of transmitters:
* Gliotransmitters - Glutamate, ATP, D-serine, prostaglandins, and neuropeptides
* Release mechanisms:
- Ca2+-dependent release - even sample transient rises in Ca can lead to release of gliotransmitters
- Vesicular release via exocytosis - large number stored in vesicles requires energy to release and is mediated by large calcium fluxes in our astrocytes - for big burst of glutamate
- Release via anion channels, hemichannels - non vesicular - P2X allows for ATP to release and anions like pumps have glutamate cytosine exchange to pump glutamate out for small number of glutamate
Adult - Maintenance of Neuronal Activity/Plasticity
* Neuron-to-glia, Glia-to-glia and Glia-to-neuron signaling
Glia-to-neuron signaling:
Ca2+-dependent vesicular release of glutamate from cultured astrocytes:
Astrocytes have synaptic machine similar to?
Astrocytes have vesicles and these vesicles can bind to and releases via?
Glial modulation of neuronal activity in the retina:
Glial cells can both?
Inhibition due to glial release of?
Astrocyte release ATP as an?
Ca2+-dependent vesicular release of glutamate from cultured astrocytes
- Astrocytes have synaptic machine similar to neurons so no AP have Ca
- Astrocytes have vesicles and these vesicles can bind to and releases via exocytosis which requires calcium flux
Glial modulation of neuronal activity in the retina:
- Glial cells can both excite and inhibit light-evoked spike activity of retinal ganglion cells
- Inhibition due to glial release of ATP and activation of neuronal adenosine receptors
- Astrocyte release ATP as an inhibitory gliotransmitter bc they convert it to adenosine where it acts as inhibitory on neuronal adenosine receptors
Adult - Maintenance of Neuronal Activity/Plasticity
* Neuron-to-glia, Glia-to-glia and Glia-to-neuron signaling
Glia to glia signaling
Calcium waves in glial cells - primarily in?
Intercellular Ca2+ waves propagated by two mechanisms?
Propagated waves could modulate?
Ca2+ waves occur in BLANK AND IN?
Calcium waves in glial cells - primarily in protoplasmic astrocytes bc Ca flux via gap junctions is a big way this occurs
Intercellular Ca2+ waves propagated by two mechanisms
- Diffusion of IP3 through gap junctions - IP3 induces release of Ca from endoplasmic reticulum stores
- Release of ATP and activation of purinergic receptors (slower moving) - can be protoplasmic or fibrous
Propagated waves could modulate distant synapses, signal to blood vessels - astrocytes in one brian area influence a far way activity without needing to release factors
Ca2+ waves occur in vivo
In the retina & cerebellum
In Alzheimer’s mice, near beta amyloid plaques
Which of the following factors released by astrocytes lead to inhibition of neuronal networks via activation of receptors on interneurons?
a. Glutamate
b. ATP
c. BDNF
d. Calcium
ATP
Glial regulation of blood flow
Functional hyperemia: ?
Glia may mediate neurovascular coupling in the CNS
- Neuron-to-glia signaling - Mediated by?
- Glial stimulation can evoke BLANK - Mediated by?
- Glial-evoked vasodilation in the?
In vivo: ?
Glial stimulation evokes BLANK
Vasodilation mediated by production of BLANK
Neurovascular coupling in BLANK
Functional hyperemia:
- Increased blood flow in active brain regions
- Basis of functional brain imaging (fMRI)
Glia may mediate neurovascular coupling in the CNS
Neuron-to-glia signaling - Mediated by glutamate & ATP release from neurons
Glial stimulation can evoke dilation of arterioles - Mediated by production of arachidonic acid metabolites
Glial-evoked vasodilation in the retina
In vivo: cortical glial cells stimulated by photolysis of caged-Ca2+
Glial stimulation evokes vasodilation
Vasodilation mediated by production of PGE2
Neurovascular coupling in the brain
