MCN 1 Flashcards
What happens in the choroid plexus?
Wastes and unnecessary solutes are exchanged for glucose, oxygen, vitamins and ions from the blood
How much roughly does the adult human brain weigh?
1.5kg
What are the functions of CSF?
To protect the brain from mechanical damage
Removes excess K ions and NTs
Carries a no. Of secreted mediators to the brain parenchyma
What are the three layers of the meninges?
The pia mater
Arachnoidea spinalis
The dura mater
What are arachnoidal villi?
Protusions in which liquid/blood transfer occurs in the brain
What is hydrocephalus?
A condition in which the ventricles have become enlarged in a newborn child
When neural crest cells are treated with glucocorticoid hormones what will they become?
Chromaffin cells
When neural crest cells are treated with wnt, what will they become?
Sensory neurons
What are the sections of the spinal cord and how many vertebrae are in each?
Cervical - 8 Thoracic - 12 Lumbar - 5 Sacral - 5 Coccygael - 1
What is the motor unit?
The muscle fibres innervated by a single motor neuron
What does the Choroid Plexus consist of?
Capillaries folded extensively
What are the components of the basal ganglia?
Caudate nucleus
Putamen
Globus pallidus
Where are the basal ganglia located?
Underneath the insula which is under the frontal and temporal lobes
What do commisural fibres do?
Interconnect corresponding grey Reas in the hemispheres
What is the corpus callosum?
The largest commisure fibre
In the cube test what did they find that the right brain was responsible for?
Spatial awareness and facial recognition
In the cube test what did they find that the left brain did?
Analytical skills
What are the two types of memory?
Declerative memory - can be out into words
Non-declerative memory - can’t be put into words
What are the functions of the limbic system?
Emotional brain
Consolidates and retrieves memories
Transfers memories from short term to long term via the papez circuit
Where is the hippocampus located?
In the medial temporal lobe
What does the hippocampus do?
Plays a role in memory and spatial navigation
What is the body of fornix?
A c-shaped bundle of fibres in the brain
What does the body of fornix do?
Carries signals from the hippocampus to the mammilary bodies and septal nuclei
What are the mammillary bodies?
A pair of small round bodies located at the ends of the anterior arches of the fornix. They act as a relay for impulses from the amygdala and hippocampu via the mammilo thalamic tract to the thalamus
What is the papez circuit responsible for?
Transfer of declerative memory from short term to long term
Where is the amygdala located?
In front of the hippocampus jn the anterior pole of the temporal lobe
What are the main categories of declerative memory?
Daily episodes
Words and their meanings
History
What are the main categories of non-declerative memory?
Motor skills
Associative
Priming cues
Puzzle solving skills
What is Kosikoff syndrome?
Caused by long term alcohol abuse it causes a lack of thiamine which leads to problems with long term memory
What is the function of the dentate gyrus?
Contributes to new memories and happiness regulation
What is believed to be the function of neurogenesis in the dentate gyrus?
It plays a role in new memory formation
What is the supracellular gyrus?
2 longitudinally directed strands of fibres termed the medial and longitdunial striae
What are some of the functions of the amygdala?
Passing on information
Forming memories
What is the telencephalon?
Cerebral cortex / vesicle 1a
What is the metencephalon?
The pons and cerebellum / 3a vesicle
What is the myelencephalon?
The medulla / vesicle 3b
What is the mesencephalon?
The midbrain / vesicle 2
What is the diencephalon?
The thalamus and hypothalamus / vesicle 1b
What does the spinal cerebellum do?
It helps us to build an image of our body in 3D space
What is the primary function of the cerebellum?
The alter the motor plan based on our environment
Outline the pathway of input into the cerebellum
The frontal motor/ parietal cortex projecfs to the pons which projects through the middle cerebellar peduncle to the cerebellar cortex.
Also the inferior olive, spinal cord and vestibular nucleus project to the cerebellar cortex through the inferior cerebellar peduncle
Outline the pathway for output from the cerebellum
The cerebellar cortex projects to the deep cereballer nuclei which project via the superior cerebellar peduncle to the thalamus which projects to the primary motor and premotor cortex
What happens to a patient with a damaged cerebellum?
They can’t maintain their balance
Outline the direct pathway for the basal ganglia
The caudate and putamen inhibit the internal globus pallidus which inhibits the thalamus which excites the frontal cortex
Which germ layer is the nervous system derived from?
The ectoderm
Where is the organiser in vertebrate development?
The dorsal lip of the blastoporous
In vertebrates how does neural determination of cell fate work?
The default pathway is to become a neuron. So in order to do this the organizer releases BMP inhibitors which prevent the cell becoming epidermis.
Name 2 BMP inhibitors
Chordin
Noggin
How does BMP signalling work?
- After the ligand has bound to the type 2 receptor it recruits type 1 and phosphorylates it activiating RI kinase activity.
- R1 phosphorylates R-Smad which interacts with co-smad and with importin for nuclear import
- The Smads are translocated to the nucleus. nuclear TF associated with the complex and activates the target genes
How many ommatidia are there in an average Drosophila eye?
about 800
How many photoreceptors are there in one ommatidia?
8
What is the site of phototransduction in an ommatidia?
Rhabdomere
What does the Lobula do?
Phototaxis, Colour vision and polarized light vision
What does the Lobula plate do?
Motion Vision
What is the mechanism of phototransduction in the Drosophila eye?
Rhodopsin activates Gq which activates PLC which activates TRP channels
What is the mutation in sevenless?
The R7 photoreceptor doesn’t work therefore the flies can’t see UV
What is an imaginal disc?
A thickening of the epidermis in the larvae which becomes an appendage in adulthood
What does a Gal4 expression of the Pax gene cause in flies?
Eyes to develop in legs or antennae
What is the signal pahthway for eye specification in drosophila?
TOY –> EY –> EY –> SO and EYA –> DAC –> Eye Specification
What is the signal pathway for founder cell spacing in Drosophila?
Delta –> Notch –I Atonal Ommatidium FOunder Cell R8
What is the signal pathway dor pigment cell lattice assembly in Drosophila?
Delta –> Notch –> Apoptosis I– EGFR
What does boss do?
It is localized in R8 and signals to neighbouring cell with the sevenless receptor causing R7 to develop
How do you identify a signalling cascade?
Perform genetic enhancer and suppressor screens
Outline the MAPK pathway
Receptor Tyrosine Kinase –> SH2 –> SH3 –> SOS –> Ras –> Raf –> MAPKK –> MAPK –> Erk1/2 –> TF –> Alteration in transcription
Define self renewal
The ability to go through numerous cycles of cell division undifferentiatied
Define potency
the capacity to differentiate into specialized cell types
Define totipotent
Able to differentiate into cell embryonic and extraembryonic cell fates
Define pluripotent
all embryonic cell fates
Outline how to grow a hESC culture
Isolate inner mass from blastocyst –> Grow on an irradiated culture of mouse fibroblast feeder cells –> dissocaite the cells and move to new feeder cells –> culture
What are the key regulators of pluripotency?
Oct 4, Sox 2 and NANOG
What is the best method of differentiating our own ESCs?
Injecting them into a mouse brain
Describe the morphology of a mouse SC culture
Dense with a high nucleus/cytoplasm ration and a dome like structure
What is the success rate of human iPSCs?
1-5%
What are the 4 strategies to induce reprograming of somatic cells?
Nuclear Transfer, Cell Fusion, Cell Explantation and Virus infection
Outline the process of an undirected in vitro differentation assat
Generate free floating embryoid bodies in the presences of 10-15% FCS then culture for 1-3 weeks as EB on the plate
What are the regions of adult neurogenesis?
Dentate gyrus and the ventricleolfactory bulb
What are the stages of adult neurogenesis?
Type 1 - Radial glial like SC –> Type 2 Transiently amplifying progenitor –> type 3 –> Early post mitotic maturation phase –> late post mitotic maturation phase
What is synaptic plasticity?
Activity dependent modification of the strength or efficacy of synaptic transmission at pre-existing synapses
What is the name of the animal that Eric Kandel experimented on?
Apysia Californica
What is habituation?
No response to a repeated weak stimulis
what is the mechanism for habituation?
Less glutamate is released
What is sensitization?
Animal becomes more responsive after combined stimulation of a strong and weak stimulus
What is the mechanism underlying short-term sensitization?
5-HT binds to pre-synaptic GPCRs –> cAMP increase –> PKA activation –> K+ channel phosphorylation –> More Ca channels open during the pre-synaptic depolarisation –> more glu
What is the mechanism underlying long term senstisation?
Repetitive pairing of shock and touch lead to CREB phosphorylation cauisng it to bind to CREs int he regulatory regions of nuclear DNA increasing the rate of transcription of downstream genes
Where does the preferent pathway project from and to?
Entorhinal cortex __> Granular cortex of the dentate gyrus
Where does the Mossy fibre pathway project from and to?
Dentate gyrus –> Ca3 pyramidal cells
Where do the Schaffer collateral fibres project from and to?
Excitatory CA3 –> CA1
What is the mechanism of LTP?
Tetanic stimulus removes the Mg block from the NMDA receptor leading to increased calcium inlfux –>CREB activates transcription of more AMPAR
How does LTP change the pre and post synaptic terminals?
Increases the no. of AMPA receptors on the post-synaptic terminal
Increases the no. of vesicles in the pre-synaptic terminal
Increases the SA of the post synaptic membrane
What is the mechanism underlying LTD
AMPA R are internalised
What induces LTD?
Prolonged low frequency stimulation i.e. 10-15 minutes of 1Hz
Outline how cerebellar LTD works
It is induced by the combined firing of the parallel fibre and climbing fibre synapses –> Glu binds to AMPA and mGLuR –> leads to PLC activation –> increase in IP3 and DAG –> opening of Ca channels on the ER and increase in PKC activation –> phosphorylation of AMPAR –> internalisation of AMPAR
What is spike dependent timing plasticity?
Synaptic plasticity dependent precisely upon the timing of events so:
PRE before POST –> LTP
POST before PRE –> LTD
What is the critical period for the cat’s eye experiment?
4 weeks to 1 year of life (ideally 4 months)
Where are ocular dominance columns located?
In layer IV ofthe primary visual cortex
What seperates the occipital and parietal lobes?
The parieto-occipital sulcus
Where is the primary visual cortex concentrated?
At the calcarine sulcus
What does the fronal cortex do?
Logical thoughts - it is in direct competition with the limbic system and can be overcome by it
How do neurons move from the ventricle to the surface?
Differentiate into radial glial cells which are then used to get cells to the surface to become the cerebral cortex
What is the function of the temporal lobe?
audition
What causes spina bifida?
If the posterior end of the neural pore hasn’t closed by day 27
What can prevent spina bifida?
The mother taking folic acid (vitamin B12)
What is Anencephaly?
When the cephalic end of the neural pore hasn’t closed meaning that part of the brain, skull and scalp are missing.
What is the ballooning of the early embryonic brain caused by?
Positive fluid pressure causing the presencephalon and rhombencephon to dilate
What does the insular cortex do?
Visual and autonomic function incl. taste
What is the insula?
Cortex and parts of the cerebellum closest to the diencephalon
What is the name of a fan shaped growth cone?
Lamellipodia
What is the name of spikey growth cones?
Filopodia
What are the three phases of axon growth?
Protrusion - extension of the lamellipodia and filopodia
Engorgement - swelling by engulfement
Consolidation - growth cone narrows and becomes part of axon
How does Slit affect axonal growth?
Slit activates CLASP which stailizes the MTs leading to pausng of growth
How goes NGF affect axonal growth?
It inhibits the phosphorylation of APC causing MT assembly causing axon extension
Explain the guidance mechanism for the midline of the Drosophila ventral nerve cord
The midline contains Slit (chemorepellents) which repel any axons containing Robo receptors. Therefore in order for it to cross the axon Robo must be downregulated. To prevent recrossing once passed the midline Robo is reactivated.
Outline the vertebrate neural tube model for axonal guidance
The floorplate releases Netrin which the DCC inaxons are attracted to.
They also use the Robo/Slit system in which Robo 1 and 2 are repulsed by slit. These are inhibited by Robo 3 therefore for midline crossing Robo 3 is active. To prevent recrossing Robo 3 is downregulated afterwards
What does mutations in robo 3 cause in humans?
Horizontal Gaze Palsy with progressive scoliosis
What is a semamorphin?
A short range repellent which increases actomyosin contraction and destabilises MTs
How are axons directed towards the brain?
BMP is repulsive for commisural neurons HH attracts c-nerurons to the floorplate WNT attreacts c-neurons towards the brain WNT is repulsive for CST neurons WNT action depends on receptor type
How does WNT signalling work?
The frizzled receptor binds WNT causing LRP to be bound. This binds Axin which allows B-Catenin to be free to increase transcription
How is the NMJ synapse formed?
Growth cone approaches muscle fibre. Bidirectional signalling occurs as the growth cone releases agrin and the muscle expresses the agrin receptor LRP4 and co=receptor MUSK this leads to clustering of the ACh receptor which signals back to te axon.
What is synapse elimination?
The concept that if a synapse is rarely used it will be refined or disappear.