bms 236-Developmental Neuro Flashcards
1
Q
Do reptilian brains have a cerebellum? Prefrontal cortex? Nerves sorted into special sensory modules e.g. vision?
A
Yes- cerebellum
Yes- sensory modules
2
Q
Mammalian brains now have a limbic system, this includes..?
A
Thalamus: integrates sensory information and allow them to be used together. tells signals where to go.
Hypothalamus: regulate the endocrine system and body temp etc.
Hippocampus &amygdala- crude memory
3
Q
Changes in the human brain?
A
Larger cortex, e.g. prefrontal cortex allowing for higher level thinking.
Development of the Neocortex
4
Q
Name where the 4 lobes are? And what for?
A
Frontal-personality (at front)
Temporal- Deep inside e.g. Hippocampus (side near temples)
Parietal- mathematical (large in einstein- parents must have been so proud)(at top near back (where parents would tap you on the head))
Occipital- visual (opticians) (back of head)
5
Q
Difference between Brocas area and Wernicke’s?
A
Brocas- speech making (e.g think of the girl who couldnt speak- brocas aphasia)
Wernicke- grammatical rules (e.g. the man who made no sense)
6
Q
Brain has plasticity throughout life, what is one area this is very evident in?
A
Hippocampus- making new memories
7
Q
What do single celled organisms share with our current nervous system?
A
Receptive and responsive to environment.
Spontaneous
Light sensitive eyespot
They then respond to this by moving using flagella.
8
Q
What comes with becoming multicellular?
A
Specificity
9
Q
In a sea sponge flow rate of water is regulated by specialised muscle like ….. which respond to stretch receptors.
A
myocytes
10
Q
The first neurons probably developed from ……. cells in the ectoderm. These then migrated …
A
sensorimotor
downwards
11
Q
Gene expression in a cell is governed by which two things?
A
Intrinsic factors e.g transcription factors
Extrinsic factors e.g morphogens
12
Q
How does the neurogenic region arise?
A
It starts as ectoderm but bmp signalling is inhibited in certain cells and these become neural. This bmp inhibitor is either Chordin or Noggin, and is expressed by the organiser/node on the dorsal side.
The developing blastula secretes bmp which induces ectoderm cells to become epidermal skin cells.
13
Q
What is the invertebrate homologue of chordin and Bmp?
A
Chordin: sog
Bmp: dpp
These are on the opposite side, so whereas Chordin is expressed Dorsaly, sog is ventral
14
Q
What is the spermanns organiser?
A
Region of mesoderm that induces formation of the neural plate from endoderm. Under the influlence of transcription factors such as Gse the organiser expresses BMP inhibitors
15
Q
The primary motor cortex projects via the …… tract to the …. The middle level is the ….
A
Corticospinal tract
Spinal cord
brainstem
16
Q
what does the primary motor cortex do?
A
It regulates motor tracts originating in the brain stem
17
Q
What does the brainstem do in motor control?
A
It regulates movements, and controls distal limbs (as well as autonomic system)
18
Q
What does the spinal cord do in motor control?
A
Reflexes, either monosynaptic or poly, and automated motor movements such as walking
19
Q
Fun fact: Why can’t babies walk early on?
A
Their corticospinal tract isn’t fully myelinated.
20
Q
Hierarchical arrangement of the motor system?
A
Primary motor cortex to brainstem is via Upper motor
neurons, and brainstem to spinal cord is via Lower motor neurons.
21
Q
Artificially stimulating the PMC only causes jerks so what two other systems are involved? Where do these project to?
A
Cerebellum: Mostly PMC (via thalamus), but also directly to brainstem,
Basal Ganglia: PMC (UMNs)
22
Q
What does the basal ganglia and cerebellum do in terms of motor control?
A
Receives info from many different areas, projects to the PMC via thalamus. Monitors the commands going down to ensure appropriate for the environment. If not appropriate, send correction signals to motor cortex. Basal ganglia terminates excess movements.
23
Q
How was the motor cortex found?
A
1870- electrical stimulus to different areas caused movements on opposite sides of the body.
24
Q
Where is the motor cortex?
A
Brodmanns area 4, located in the frontal lobe just before the central sulcus. It is topologically arranged (think man with big hands and lips)
25
what do Upper motor neurons do?
From cerebral cortex or brainstem. Project to the lower motor neurons via interneurons, for planning, initiating and directing movements
26
What are the two upper motor neuron pathways?
Direct: UMNs axons from the cerebral cortex Input to LMN
Indirect: UMNs axons from brainstem input to LMNs. Inputs from cerebellum and basal ganglia also join to these.
27
summary: UMN- Interneurons- LMNS- muscle
:)
28
change in the muscle tension is detected by?
Golgi tendon organ
29
Change in muscle length Is detected by?
Spindle
30
How is tension created within the muscle?
Alpha motor neurons cause the Extrafusal muscles to contract. (if someone is extra they may cause tension within a group)
31
What do intrafusal skeletal muscles do?
proprioceptors that detect the amount and rate of change of a muscle length. Examples are Ia, II, I or Y.
32
Which fibres are afferents of the intrafusal and which are efferents? Difference in structure? Function?
Afferents: Ia, II, I
Efferents: Y (gamma)
Afferents, wrap around. These give sensory info to CNS as these coils are pulled apart.
Efferents just join to the fibres from the CNS. Gather in the slack to keep tension (make extrafusal muscles contract os spindle shortens)
33
Ia vs II intrafusal structure? Function?
Ia- largest neuron in body- wrap around the fibres. This relays info as stretches (as coils get further apart)
II- Flower spray ending on fibres. Relays info on final amount of stretch.
34
Intrafusal vs extrafusal placement around the fibre?
Intrafusal are within the spindle, whereas extrafusal outside.
35
What is the impact of serotonin and noradrenaline on proprioception?
serotonin increases the AP firing of gamma motor neurons, better at transmitting stretch as more taut
NA decreases.
36
What is the tendon jerk reflex?
Hit knee- Stretch muscle- Ia intrafusal muscles are fired-causes muscle to stretch and jerk (extrafusal). This happens as is monosynaptic.
37
Which experiment proved that Sperry’s theory was right over Weiss’s?
If cut optic nerve and remove temoral retina (these axons grow from same place but different target) do the growing optic nerves grow straight to the right target or do they take over temoral retina target then prune back? Straight to correct target.
Also, cut and move chick embryo axon and regrows back to same target.
38
Sperrys theory vs Weiss?
Sperry: Computational model: Axon outgrowth is specific to the target,
Weiss: Resonance Theory: Axon growth is to everywhere then pruned back.
39
What is the Labelled pathway hypothesis?
If ablate a target or axon cue, the axon stalls. Early axons (pioneers) make axon scaffolds for later axons to follow.
E.g. subplate neurons project from cortex to thalamus then lateral geniculate nucleus neurons follow. And if ablate subplate early LGN don't develop here.
40
Experiment to evidence cues?
Grasshopper if ablate CX1 cue in limb bud, Ti 1 doesn't cross the limb bud, path changed.
41
In the limb bud of the grasshopper what guides the Ti 1 axons?
Semaforins, and CX1 cue to cross the limb bud (Semaforins along) also Sema 2 secreted signal.
42
What is the arrangement of an axon growth cone?
Central part made of microtubules. Then the growing and retreating filopodium is made out of actin in bundles. The following llamellae is crosslinked f actin.
43
How does the growth cone explore the environment and move?
Actin treadmilling constantly is happening. This is the continuous movement of actin polymerising and breaking down. If the growth cone is attracted to a signal, this treadmilling is slowed, yet the same f Actin subunits are added, so the filapodium grows.
44
How do growth cones affect the actin treadmilling?
The growth cone receptors sense the growth cue, and a molecule clutch is engaged in the filapodium. This causes the slowing of actin treadmilling.
In addition; an actin myosin tubulin link pulls in the MT central unit into the extending filapodium causing further growth.
45
what if a filapodium interacts with a repulsion (non- permissive) contact?
The filapodium collapse but leave behind a conection (remembering)
46
What are semaphorins?
Inhibitory cues. membrane bound or secreted.
47
What are permissive cues? (contact attractants)
A permissive media is a media that an axon can adhere to and can follow the path of as it is easier to grow on. Blocking this doesn't change the direction just slows. e.g. optic nerve follows laminin. (only in certain concentration therefore not instructive)
Adhesion growth relationship not simple.
48
Example of non-permissive cues?
Semaphorin at limb boundary ensure don't go into until CX1. e.g. K/o Sema3a don't reach target, or Sema1 antibodes block, cross limb bud too early.
49
What are Ephrins?
non-permissive. Cause repulsion between cells. Detected by Ephs, they line the rhombomeres so enable compartmentation. Later also keep axons out of certain areas, and also create topographical maps.
50
Example of Chemoattraction in axons?
Commisural sensory relay neurons are attracted to nectin in the floorplate (also SHH). (bees pick up nectar from the floor next to hedgehogs)
If dissect out and purify can find nectin.
51
Example of Chemorepulsion in axons?
Roofplate secretes BMP repels from Commisural sensory relay neurons from the roof. e.g. BMP7
52
Summarise examples of the 4 cues?
Chemoattractants: Nectrin in floorplate and SHH
Chemorepulsions: Semaphorins, Ephrins
Contact attractants: Permissive e.g. laminin optic nerve
Contract repulsions: BMP in roofplate. (CSRN)
53
How can tell than Nectrin doesn't work alone?
Experiment:
Some CSRN axons reach floorplate without Nectrin.
K/o of either SMO (receptor for SHH), or Nectrin
54
How do you create a K/o by cre- recombinase?
Bacteriophage P1 can insert specific DNA sequences in a host genome. These sites are a specific 34 base sequence called LoxP. Two of these can be placed either side of the target gene. Cre Recombinase can bind and cut the host DNA and join to another cut LoxP site.
55
How can you create tissue specific recombination?
cross Cre- recombination mouse (under tissue specific promoter: Wnt 1 for Cre) and a mouse with floxed (LoxP either side of target gene) gene in germ line in all tissues.
Result: in all tissue bar target, floxed genes but no cre, in target tissue, target gene been spliced out and cre expressed.
56
What is an example of axons reprogramming their response to cues?
CSRN- after crossing the midline lose responsiveness to nectin.
Experiment: Put an ectopic floor plate (Nectin) after crossed the midline and the axon does not respond to it, but sees it as inhibitory. WHY DOESN'T STAY IN THE MIDLINE.
57
Why after crossing the midline do CSRN see the floorplate as inhibitory?
Semaphorins and Slits (inhibitory proteins) in floorplate and ventral SC guide axons. After cross the midline levels of the receptor for Slits increases so see it as inhibitory.
58
What is the receptor for inhibitory Slit?
Robo- Roundabout (because K/O of keeps going round in midline- no inhibition by Slit)
59
Robo levels are high in axons that .....
do not cross the midline.
60
What prevents Robo reaching the cell surface?
Comm- Commisureless (because K/O doesn't cross the midline and commissure) so doesn't reach Slit inhibition.
Vertebrate homologue Robo1 expressed before and after crossing and doesn't commissure.
Rig1 expressed before crossing, block Robo1 until after crossed (K/O Rig1 doesn't reach floorplate)
61
Comm expression in axons?
Expressed before crossing the midline, after cross switched off (so more robo, so respond to inhibitory slits)
62
How can follower axons follow an axon scaffold?
Cell adhesion molecules (CAMs) e.g. Fas II (can cause aggregation)
63
Fas II K/o?
| Overexpression?
In flies, defasculated axons not in fascicles.
| Overexpression: 'bypass' phenotype, fail to defasculate from scaffold so miss target.
64
Rods are active( depolarise) in .... light, whereas cones are active in ..... light
whereas in the opposite they hyperpolarise.
Rods active in dim
| Cones active in bright (cones bright orange colour)
65
After the photoreceptor depolarises, what's next in the trasduction?
Bipolar cells
- On bipolar cells are on in the light
- Off bipolar cells are off in the light
e. g. in rods depolarisation (active in dim light) inhibits on biplolar cells, activate off.
e. g. in cones depolarisation (bright light) depolarises on bipolar cells
66
How does the transduction from light to releasing glutamate (or not) happen in rods?
Normally the sodium channels are open, causing depolarisation which releases glutamate.
Rhodopsin light-transducin GDP to GTP, activates PDE.
This converts cGMP to GMP which closes the sodium channels, hyperpolarising so not releasing gluatmate.
67
What dictates that the off bipolar cells ...... with glutamate, and on ...... with glutamate?
off depolarise with glutamate as they have excitatory ionotophic receptors
on hyperpolarise with glutamate as they have inhibitory metabotrophic receptors
68
The bipolar cells inhibit ..... cells
ganglion cells
| and amacrine cells
69
What is a receptive field?
an area in the retina which when illuminated activates a visual neuron.
70
can have on and off centre receptive fields what does this mean?
On centre receptive field more AP's fires when lit in the middle, but not when the surround is lit. When all is lit together these contradict, and no more AP's are fired.
71
why when the surround and the centre are lit do they contradict?
Because of the horizontal cells feeding back.
And many photopreceptors converge onto one bipolar cell, so if some are activated and some arent they cancel each other out. One hyperpolarised v one depolarised.
72
What are the layers called in the eye?
photoreceptor to bipolar and horizontal in the outer plexiform layer, then ganglion and amacrine in the inner plexiform layer.
73
What is unique about photoreceptor synapses?
They can release vesicles of NT constantly, just the release rate goes up or down (graded potential). They are ribbon synapses- always vesicles in the active zone.
74
What areas of the brain recieves visual info, completing the most processing?
LGN- Lateral Geniculate nucleus in thalamus pre-processes before sent to the visual cortex.
Cortext also feeds back to here.
75
What are the two visual pathways from the primary visual cortex?
Ventral- 'What' object is- temporal (get temporal headache after venting about what is wrong)
Dorsal- 'Where' spatial location- parietal (Go through the door with parents to get where you want)
76
Function of:
| Pupil, lens, fovea
Pupil dictates amount of light through to retina
Lens focuses the image on fovea
Fovea part of retina with the highest acuity (cones mostly)
77
In off bipolar cells if stimulate the centre of rods receptive field what happens?
Rods hyperpolarise, off bipolar cell hyperpolarises
78
In off bipolar cells if stimulate the surround of rods receptive field what happens?
The rod photoreceptor depolarises, and the surround cells hyperpolarise. This gets fed to the horizontal cells which hyperpolarise. This has an inhibitory affect on the photoreceptors in the centre so they depolarise. So bipolar cell depolarises
79
What if it's an on centre receptive field in cones? If light in centre? Light surround?
Light in centre: depolarises
| Light in surround: hyperpolarises
80
What if the whole receptive field is lit?
the amount of depolarisation=the amount of hyperpolarisation by horizontal or amacrine cells on the bipolar or ganglion cell, therefore cancel each other out.
81
What are the two types of ganglion cell? How common?
Parvocellular (80%) and Magnocellular (10%)
82
What are the two shapes of the dendritic fields and body for the two types of ganglion cells?
Parvocellular have a miget dendritic field with more dense body, whereas magnocellular have a parasol shape with lots of dendrites.
83
What do the shapes of the two types of ganglion cells mean for function?
Parvocellular shorter dendritic field- higher acuity and detail, lower sensitivity to light.
Magnocellular- less high acuity, but high sensitivity to light
84
Different spiking patterns for the two ganglion cell types? Function?
Parvocellular- 'sustained' spike for quite a while. Making conduction velocity slower.
Magnocellular- 'Transient' burst spiking- good for tranferring information (less high acuity) quickly.
85
Primary function of two types of ganglion cells then (summary):
Parvocellular: Midget, high acuity, low light, sustained spiking, slower velocity = FORM AND COLOUR (ventral)
Magnocellular: Parasol, low acuity, high sesnitivity to light, short spiking, high speed= MOTION DETECTION (dorsal stream)
86
How do the photoreceptors adapt to contrast?
Depression- If high temporal contrast initial high spiking but reduces sensitivity over time as adapts
Facilitation- If low contrast or recovering from depression.
87
During the day we mostly use ..... photoreceptors? Why?
Cones. These fire at bright light, whereas the rods saturate.
88
Cone cells have differet spectral sensitivities why?
Depending on optimum wavelength there are three opsins, red, green, blue so can see in colour depending on amount that fire where etc.
89
If damage dorsal stream?
Trouble processing motion
90
How does direction motion relate to spiking?
If in the preferred direction there is lots of spiking, whereas little if in the null direction.
Excitatory info if in the right direction, but inhibitory if in the other. Depolarisation not sufficient to spike as inhibitory greater than excitatory.
91
What are the three types of cell found in the V1?
Simple, complex and hypercomplex
92
Ablation of ..... leads to disappearance of the orientating reflex
Optic tectum or superior colliculus in lower vertebrates.
93
What did the Hubel and wiesel experiment find?
The three types of cells in the V1, also that in the cat V1 cortex everytime light was shone neurons fired, but some also fired when the light stopped shining. (inhibitory surround cells) but if cover whole receptive field none fired.
94
When would the simple cells fire? not?
They fire more when there is light shone on the centre, but stop firing if outside field. Don't fire if all over field and surround, and don't fire if the orientation of the light has changed unfavourably.
95
Why would the simple cells fire in some but not in other orientations?
Depends on orientation, as the Lateral geniculate nucleus neurons often line up in a line converging to the simple cell, so when all of these experience light in this orientation all fire, whereas if only some do, may also have surround inhibition which overrides and cancels out the excitation.
96
Structure of the Lateral Geniculate Cortex?
In thalamus. Relay centre.
6 layers, with layers alternating input from each eye.
2 of these, so contralateral to layers 1,4,6
ipsilateral 2,3,5.
1-2= magnocellular project
3-6= Parvocellular
97
What are retinotopic maps?
Neighbouring photoreceptors feed into neighbouring parts of the brain so image stays in tact.
98
Why are receptive fields of the LGN similar to ganglion receptive fields?
Because 1:1 connection to LGN projection neurons.
99
sequence of the ventral stream?
Vent= What
| Parvocellular ganglion cells-LGN parvo-V1-V2-V4- IT neurons shows form (inferior temporal)
100
Sequence of the Dorsal stream?
Dosal=motion
| Magnocelluar ganglion cels- LGN magno- V1-V2-V3- Parietal (some feeds to v4 for colour processing) to detect movement
101
How does object recognition largely work?
if see an object, certain neurons in brain fire for that object, so if encounter again and the same neurons fire we recognise it as the same as before e.g. one specific cell- Jennifer aniston cell.
102
What is the hierarchical sequence of object recognition?
(V1)Detection of edges- (V2,V4) detection of combination of edges and contours- (temporal)detection of key shapes e.g. face- detection from one point of view e.g. front- particular person or car- categorization e.g a human, animal
(increases complexity along the ventral stream and increase in receptive field size)
103
Other names for the dorsal and ventral streams?
```
Temporal= Ventral (get a temper as you vent)
Parietal= Dorsal (walk through door with parents)
```
104
What is an experiment to investigate ocular dominance? Why?
Radioactive proline in one eye- can see projects to only certain layers of LGN
Helps see in 3D and interpret object closeness to each eye etc.
105
The ocular dominance columns have blobs that detect? and on another axis through show? (picture a 3D grid)
one axis, the columns from alternating eyes, one blobs show colour, third axis is orientation and direction showing edges- together build up a picture.
Hypercolumn when shown together.
Other feature= layers
106
How do complex neurons differ to simple?
Complex respond to light anywhere in receptive field, but still orientation can affect.
107
How do hypercomplex cells differ from complex?
like complex they respond to light anywhere in receptive field, but if its say less than half in, and half in another receptive field, it will stop firing.
If then change the orientation in this neighbouring receptive field starts spiking again (e.g. the inhibition has no gone)
'end-stopped'
108
What are computation models used for?
Estimating the receptive fields in V1- apply thousands of images, record spiking and average to get receptive field of a neuron.
109
The visual cortex receives inputs from ..... and outputs via?
LGN
| pyramidal and satellite cells to other cortical areas, LGN, SC
110
What does the density of calcium channels near the active zone in the pre alter?
If lots of calcium channels near, have higher sensitivity to depolarisation, so the less depolarisation is needed for synaptic release, whereas if there are few less sensitive
111
What can sense Ca sensitivity and able to signal to vesicles to bring them closer to the active site?
Synaptotagmin
112
What three things can bring the synaptic vesicle closer to the PM active site for release?
Syntaxin
SNAP 25
Synaptobrevin
113
What are the three pools of synaptic vesicles sets? Where are these?
Readily releasable pool: on the PM
Proximal pool: At active site but not on PM- after release these move down into the readily releasable pool.
Reserve or resting pool- Those that are made go here first.
114
What is the refractory period of vesicle release?
The readily releasable pool of vesicles has been depleted so cannot release more until recycled.
115
What three types of channels and examples can glutamate bind to?
NMDA- ionotropic receptor (also mg voltage gated)
AMPA- ionotropic receptor
Both linked to channel so release Na into the cell- causing depolarisation if glutamate binds. NMDA also selective for Ca so influx in.
Mglut metabotropic G-protein coupled- Gq or Gs.
116
Why use model organisms for memory experiments?
Large neurons, simple circuits, less sensitive to temperature changes, mapping can be done by labelling early and seeing connections
stereotypical- e.g. exact number
117
What is habituation?
Sleeping near train tracks
Desensitize to innocuous stimuli repeated
e.g. aplasia sea snail siphon- if repeatedly tap the gil will stop retracting.
118
What is sensitization?
NS responds to a stimulus more and more e.g. if shock the aplasia siphon the gill will keep retracting with touch.
119
what is the aplasia's siphon neuronal circuit? (simplest)
Siphon has a sensory neuron, which synapses to a motor neuron going to the gill muscle
(therefore tap on siphon, gill retracts)
120
How can an experiement be done to tell where in the neuronal circuit there is desensitization in the aplasia?
Either at sensory terminals of sensory, been motor and sensory, or motor response.
Test: use electrodes to stimulate the two individually and see responses downstream- if stimulate motor same response, if stimulate sensory skin same depolarisation of the sensory neuron therefore between the two neurons.
121
How does the synapse between the motor and sensoy neuron of the aplasia habituate?
The number of vesicles that can be released is decreased, so for the same depolarisation on pre, post is smaller. (lower quantal release)
122
How does the aplasia sensitize e.g. to a shock?
There is a third neuron involved, L29, serotonin is released across the cleft to the sensory neuron. There are G protein coupled receptors for 5HT, Gs, .adenyl cyclase, camp, PKA- phosphorylates K channels in synapse (which repolarise) and inactivate.
Therefore, the depolarisation is prolonged, enabling more synaptic release.
123
What is the associative learning experiment in the aplasia?
Conditioned stimulus: weak siphon touch
Unconditioned stimulus: Shock
if these are both done at the same time, will associate the two and retract gill at only a touch
124
How does the associative learning happen in the aplasia?
Serotonin is released across the synapse from L29 to Gprotein coupled receptor Gs- activates adenyl cyclase, Atp- cAMP- PKA.
Ca released in from the siphon touch (CS) increases the effect of adenyl cyclase further, so more cAMP released, so greater activation of PkA (Phosphoylate K receptors so dont work- depolarise for longer). Larger reponse that lasts longer.
125
Long term sensitization requires ...?
the nucleus e.g. gene expression changes
126
What is that paper Anton did a whole lecture on?
Lymnaea- Kemenes 2006 paper
| Non- synaptic plasticity in the snail (changes in efficacy)
127
What was the experiment in that paper Anton said about?
Association of attractive food (sucrose) US, and neutral stimulus Amyl Acetate (CS), learnt to associate the two so was attracted to the Amyl acetate due to pairing. Showed a change in behavioural feeding.
128
What are the two different cell types which are in the feeding network of the Lymnaea?
The Serotonic cerebral giant cells (CGC) which permit feeding and the CPG which permit the behaviour of feeding, if these fire feeding is possible, if don't cant.
129
What happens to the resting potential of the cells in the lumnaea in this experiment?
As see the food sources the resting potential goes up, more depolarised in the trained CGC around 24hrs later, causing the long term memory- away from neurons allowing behaviour
This leads to fictitious feeding behaviours towards amyl acetate.
130
In lymneae experiment is depolarisation of CGC neccesary? Sufficient? Evidence?
Sufficient: Yes as after 16hrs and lasts as long as the long term memory. Evidenced by artifically depolarising the CGC causes ficticious feeding behaviour
Necessary: Couldn't tell
131
What do taxi drivers have a very big of in the brain? why?
Hippocampus for spatial memory
132
What is the simplified hippocampal circuit?
inputs go through the Entorhinal cortex to dentate, Dentate to CA3 (mossy fibres) to CA1 and then output.
133
With what neurons can LTP be tested on in the hippocampus? how?
CA3 to CA1 synapse.
If stimulate CA3 for 15mins and measure amplitude in CA1 with electrode stay the same. But if do tetonic stimulation, amplitude of CA1 increases (epsp)
Largely NMDA- independent LTP- increase in vesicle release
134
What is tetonic stimulation?
HIgh frequency stimulation eg. 1000hz per s for 1s
135
If do tetonic stimulation repetitively on the CA3 neuron?
CA1 amplitude summates to a v high amplitude.
136
How could calcium be linked to LTP?
When glutamate binds to AMPA (tetanic) depolarises so NMDA mg block removed and Ca is released inwards. Kinases are activated e.g. calcium calmodulin dependent kinase CaMK 2, this phosphorylates AMPA receptors increasing channel open probability, and also AMPAfication- increase the number on the active site. (by tetanic)
These depolarise the membrane and then NMDA receptors can open. More receptors, less synaptic input needed for epsp.
137
The late stage of LTP needs...
protein synthesis
138
Early LTP relies on?
phosphorylation e.g. CaMK 2 AMPA receptors, and autophosphorylation keeps channel open. increasing ampa currents.
Also AMPAcation- calcium released from NMDA causes more AMPA receptors to fuse with the post PM.
139
Experiment to show early LTP?
Add glutamate to synapse for 20mins, after wash out got more sensitive to LTP
140
Long term LTP needs ...? Takes? WHat also is key?
Protein synthesis, about 1 hr later, also cAMP signalling
141
Why is cAMP signalling crucial for long term LTP?
It activates CREB-1, which binds to DNA and dislodges CREB-2, which blocks gene expression, whereas whe CREB-1 is phosophylated by PKA can unblock.
142
Summary long term and short LTP?
Short: Glutamate- AMPA,depolarises NMDA- Ca, AMPAcation and CaMK II phosphorylates so keep open. NMDA then mg block taken- sensitize. AMPAfication also.
Long: CaM also adenyl cyclase- cAMP- PKA- Phosphylates CREB-1, dislodges CREB2= gene expression and protein synthesis.
143
How can LTP be experimented? (mouse)
Mouse in a waterpool, after trial and error swimming finds a ledge. If repeat experiment will go straight to this ledge.
If K/O of CaMK II, learning reduced.
Or use memory enhancer drugs, learns faster. e.g AMPAKines
144
What are the two types of LTD?
Depotentiation: taking away previous potentiation
| LTD de nova: Depression where there is no previous potentiation
145
What is LTD?
Long term Depression, reduction in the efficacy of a synapse.
146
What is patient LM?
Damage to dorsal stream couldn't see motion
147
What does superior colliculus do?
Recieves sensory info from many modalilties and integrates, regulate sarccadic movements and orientation reflex.
148
What are the 4 main ways of studying vision?
Psychophysical methods e.g. illusions
lesions- show what happens if damage therefore function
Anatomical and morphology studies- how neurons actually connect and where they go
Imaging- e.g. FMRI, electrophysiology recordings
149
Why use zebrafish for vision studies?
Less ethical problems which have with higher animals e.g. primates,
Can illuminate whole brain to see electrical activity
negative: quite different so rodents and cats often used also
150
How does FMRI work?
Functional magnetic resonance imaging, used blood-oxygen-level-dependent contrast, which shows fluorescent when high oxygen to an area in the brain which is linked to acitivity.
151
How can morphological studies be done to investigate vision?
Golgi stain or fluorescence e.g. GFP, shows connections etc.
152
How can electrophysical recordings be done in experiments into vision?
Fill electrode with electrolyte, and can see spikes of individual neurons
153
What are the four cells in the cerebellum cortex?
Mossy fibres and climbing fibres input
Granule cells
purkinje fibres output
154
What are the 4 layers of the cerebellum?
(top) Molecular, purkinje, granular and white matter
155
What are the mossy fibres?
Part of the white matter. Input to the granule cells
156
What are the granule cells?
Recieve inputs from mossy fibres and send axons to the top molecular layer where they split into two parallel fibres. Outputs are then sent down the purkinje cells.
80% of cells in cerebellum are, and outnumber the mossy fibres 50:1
157
What are the purkinje fibres?
Output cells of cerebellum. Each purkinje recieves 150,000 parallel fibre synapses.
Their cell body is in the purkinje layer.
Largest cell in the cerebellum (conenct to many parallel) with fan dendritic field.
158
Wat are the climbing fibres?
Each purkinje recieves input from one climbing fibre, which wraps around the cells dedrites forming at least 1000 synapses.
These are the axons of the cells in the Inferior Olive.
159
WHat do the climbing fibres do?
Input error signals about movement inaccuracies,
160
Differece between simple spikes and complex in the cerebellum?
Simple: Purkinje fire spontaneously around 50per second (parallel can increase to over 200). Higher frequency.
Complex: From climbing fibre input, much fewer aorund 1 per second, but very reliable purkinje always fires if climbing fibre does. Unusual shape.
161
What are the ratios of cells in the cerebellum to each other?
1 mossy to 50 granule (80% of cells)
1 Purkinje recieves 150,000 synpases from horizontal fibres
1 purkinje: 1 climbing fibre
162
What does the cerebellum do?
Control movement, check is what intended and right for environment, if damaged uncordinated inaccurate movement (like drunk as particular susceptable to ethanol)
163
What is the Marr- Albus theory?
In order to make accurite movements, one must have error signals (climbing fibres)
164
What is the Decorrelation Learning rule?
The synapse between parallel and purkinje fibres are changed depending on the correlation between parallel and error signal firing.
e. g. if fire together- reduce strength of synpase (as needed error so inaccurate)
e. g if negative correlation- increase strength of synpase (no error signal needed for this movement)
Learning stops when no longer a correlation.
165
What is evidence for this decorrelation learning rule?
If stimulate a climbing fibre with an electrode at the same time as a horizontal fibre, the synapse between horizontal and purkinje will become depressed, giving a smaller EPSP. LTD
166
Example of a motor task that uses decorrelation learning rule?
Vestibular ocular reflex- e.g. as head rotates, eyes also move but in opposite direction in order to maintain a stable image so doesn't blur.
This may be an example of a strengthened error reflex, as if inactivate the flocculus region in cerebellum doesn't work.
167
Cerebellum also now thought to be involved in?
sensory prediction and active sensing (e.g. feeling an object to know what it is)
emotional and cognititive processing
Role in disorders autism, dyslexia, schizophrenia
168
What does the Cerebellum chip metaphor suggest?
The basic cells (algorithm) is the same in the cerebellum but its the external signalling that determines the diverse function.
169
If rotate a monkeys head the cerebellum ...., but if it move its own head.... why?
Fires, doesn't.
| The cerebellum responds to the unexpected, it's already learnt what to do when moves its own head.
170
How can LTD be different from LTP?
Unlike LTP can also be non-hebbian (have no presynpatic activity).
Different mechanisms, doesn't need kinases like LTP, but uses phosphatases.
171
How does the LTD between climbing fibres and horizontal fibres happen? Mechanism
The parallel fibre (probably) releases gluatamate to purkinje which binds and activates metabotrophic G coupled receptors. These a cause PIP2 into IP3 and DAG. DAG causes the PKC so be activated. phosphoylating AMPA receptors (in different place to in LTP) and causing them to be endocytosed, so less depolarisation as glutamate binds again- so LTD.
Ca in due to the depolarisation from the climbing fibre AMPA Na in. Ca further increases this action of PKC, so if co-incide LTD here.
172
Evidence for the LTD in cerebellum mechanism?
If insert endocytosis inhibitors, no LTD
173
What is an example of LTD in the hippocampus?
If a synpase of one cell active where rest isn't, this is weakened LTD.
e.g. CA3 to CA1 synpase
174
How do hippocampus example of LTD work?
Depends upon the amount of NMDA receptor activation.
If low frequency stimulus few are activated (still blocked by Mg), so very little Ca is let in, whereas lots in high frequency stimulus.
If low protein phosphatase is activated. Unphosphorylated AMPA R, reduce action= LTD
If high protein kinase is activated (CaCK II). Phosphorylated synpatic AMPA R, increase efficacy, and NMDA Mg block gone=LTP
175
What molecule not only promotes LTD but also inhibits LTP? Vice versa?
```
PP1= LTD
AKT= LDP
```
176
Hippocampal damage causes ..... damage but not ....
anterograde (cant create new memories)
| Retrograde (past)
177
What are neurotrophins?
growth factors which mantain neurons survival
178
Experiment that shows diffusible growth factor neurotrophins?
Some sarcomas secrete, so Bueker implanted sarcoma, which can promote survival of neighbouring neurons.
(also found in snake venom, mouse submaximallary gland)
179
What the Viktor Hamburg experiment?
If remove limb bud: Neuron degeneration fail to innervate where was.
Extra limb bud: Fewer apoptose, so more DRG to innervate
Limb bud secretes survival factors NGF (fast growing tissue e.g. sarcoma etc)
180
Structure of NGF 7S? Beta?
```
7S= 2a,2B,2Y
B= dimer (A and Y only in submaxillary gland maybe for storage)
```
181
Campenot experiment with neurotrophins?
If NGF taken away from the outside compartment, the axons processes retracted (gaps can let these through but not spread of NGF)
182
How does the NGF work in the campenot experiment?
NGF binds to receptors on growth cones, internalised and transported to the soma. Retrograde support to guide axons path in vitro.
183
What are the 4 receptors for the 5 types of Neurotrophins? Which bind to which?
TrkA, NGF and also NT-3 (High affinity receptor)
TrkC, NT-3
TrkB, BDNF, NT-3 and NT-4 and NT-5
p75NTR, Pro-NGF and all. (low affinity receptor)
184
WHat is the structure of Trk A?
Classic receptor tyrosine Kinase (ligand causes dimerisation and autophosphorylation).
Affects differentiation and growth.
185
WHat is different about p75 receptor?
this can promote both cell survival and cell death depending on the NT binding e.g. if pro-NGF binds causes apoptosis
186
Dependancy to NGF's can change over time- which do neurons often respond to first?
NT-3 early.Often change as reach a target.
e.g Trigeminal neurons: BDNF and NT-3 early, then NGF see on ealy route.
Different neurons have different receptors to.
187
All NGF's are synthesised in the ... form and ....
Pro- form and cleaved (can bind in pro form also e.g. Pro-NGF)
188
Placodal sensory ganglia prefer NGFs....
Crest-derived DRG's ...
SYmpathetic neurons... but not...
Placodal: BDNF and NT-3
Crest DRG: NGF, BDNF or NT-3
Sympathetic: NGF or NT-3 but BDNF
189
Some organisms like the ... have no NGF's, but have different versions e.g ?
Drosophila
GDNF (glial derived neurotrophic factor)
cytokines e.g. Macrophage stimulating factor, hepatocyte GF, ciliary NTF
Testoterone- in females, increase motor neurons to the clitoris (sex differences)
190
Example of what Glial derived neurotrophic factor can do?
Can turn Pea3 TF in motor neuron reflex circuit,
If K/O Pea3 motor neuron shape changes and circuit
(not only is the target promoting survival but also characteristics)
191
Example of how NGF's can cause circuit completion for a muscle?
Critical for monosynaptic circuits e.g stretch relfex
Muscle expresses NT-3 which induces the expression of TF Erl-81 in Ia proprioceptors guiding them to target muscle.
192
K/O for Er81?
Failure for the Ia central projection reaching the S.C ventral horn, and form stretch reflex circuit.
193
Why does blocking a NMJ with curare cause more neurons to survive?
Both pre and post neurons need to be activated at the same time for the synapse to survive. If this is uncordinated then this will cause this synpase to be outcompeted and die.
If block the nicotinic receptor with curare no uncordinated activitiy will be seen so more neuronal synapses will survive.
194
Peripheral cell death matches the ...
Tissue size, e.g. DRG's innervating limb buds show less cell death as larger tissue size to innervate
195
Significance of a somatosensory barrel and cell death?
Site where lots of cell death occurs, as 1 whisker needs to go to 1 cell in cortex.
196
How can it be proven that cell death is by apoptosis
Requires protein synthesis: add cyloheximide stops apoptosis (inhibits protein synthesis) or Actinomyosin Dwhich inhibits transcription
197
intrinsic apoptosis pathway?
DNA damage or P53 (tumour protein)- Injured mitochondrial release cytochrome C- Caspase 9 initiated- effector caspase 3- Apoptosis
198
Extrinsic apoptosis pathway?
Death ligands e.g. Ubiquitin or Fas- Death receptors- initiator caspase 8- effector caspase 3- Apoptosis
199
What does Caspase 3 do?
Cleaves proteins involved in inhibiting apoptosis, DNA repair, cell cycle and nuclear structure.
200
How does cytochrome c activate caspase 9?
Cytochrome c binds to adapter protein Apaf-1 which lines up all the caspases and cleaves them to activate.
201
How can a death ligand lead to caspase 8 activation?
E.g. Fas (a tumour necrosis factor) ligand on a cell binds to a fas receptor. The procascase join to these with the adapter protein which cleaves the procaspase 8.
202
If K/O Ced3?
NO apoptosis- requires Ced 4 as well.
| (also anti apoptotic gene Ced 9
203
In Sympathetic ganglion cells BDNF causes .... NGF causes...
apoptosis when binds to P75 (only in some parts of the brain) SUfficient and necessary
NGF in high levels causes survival
204
Pre and Pro forms of neurotransmitters?
Pre- signal peptide
| Pro- cleaved after release (Not in Pro-NGF- apoptosis if binds to p75)
205
Example of how excitation of post can result in NGF release?
e.g. glutamate bind to NMDA receptor on post, which induces the release of Ca (channels on PM and stores e.g. ryanodine)- CaMK or PKA- BDNF release. So neurons not stimulated may die
206
If two neurons synapse onto one muscle fibre and it produces pro-BDNF what determines whether survive or die?
Winner: Local stimulation causes pro-BDNF to be converted to BDNF- survive
Loser: Lack of stimualtion Pro- BDNF not cleaved, retract and if no other junctions apoptosis
207
WHat does Staurosporine do?
Inhibits protein kinases so causes apoptosis
208
```
Synaptic receptors are ...
Extrasynaptic receptors (away) are...
```
anti-apoptotic
| Pro-apoptotic
209
For functional synapse need:
Correct receptors being expressed
Synapse at correct location
Correct number of synapses made
Electrical activity matching early.
210
Sequence of events as a synpase forms? NMJ?
1. Axons with filapodia contact target and retract as tight junction forms
2. Membrane and Extracellular matrix glycoproteins are added. (Can be pre-prepared synapse site with adhesion molecules here to hold pre and post together before mature)
3. Presynaptic vesicle machinery develops, dence ECM (thickens) and receptors accumulate on post
4. Pre makes a terminal, and at a NMJ 'schwann cell capping' as coats.
211
Example of two animals varying synapsing?
Cat visual cortex- 1 month post natal
| Mouse olfactory- 1 week post natal
212
Experiment that shows that a growth cone 'talks' to its target?
If take a muscle target and attatch electrodes to Ach receptors, as growth cone gets near increases electrical activity- senses.
213
How is the site of a synapse planned?
Astrocytes may cover part of the target so cant synapse here, may have pre-prepared sited with cadherines and adhesion molecules here.
214
How do the receptors cluster near a synapase on post? (not why)
As an axon approaches the muscle, nuclei makes more AchR all at surface.
As the axon contacts the Ach receptors cluster near and turning off mRNA in nucleuses further away from the synpase, so just increase near.
215
What evidenced that in the lymnaea experiment the depolarisation of the CGC impacted the post?
Causes greater EPSP on the post, if use patch clamp pre and post can see this.
This increased over time as the depolarisation caused more Ca in synapse so depolarising it more.
216
How does the resting membrane potential change thrugh development?
Falls during development, to become negative, as pump ions out e.g. Na+.
217
How do glia change the ion concentrations in development?
Changes the outside K concentration around neurons- from 35mM to 3mM, as the number of astocytes increases and mop up K+.
218
What 3 things that change in neurons as develop?
Membrane potential becomes negative
Input resistance falls- current flows more easily
Membrane time constant drops- How quickly a current can be changed into a signal, depends on resistance and capacitance (ability to store charge- increases as they grow)
Calcium dependent long AP early in development, then becomes Na short AP
Also K extracellular 35mM to 3mM
219
WHat are Rohon Beard Cells?
Form very early in development, before DRG, mechanosensory cells, calcium driven AP, elongated plateau phase.
These gradually get shorter as the K channel functions and repolarises earlier, and changes to Na, which snap shut quickly.
220
What is a delayed rectifier?
A unidirectional channel that opens some time after its voltage threshold has been reached e.g. the K+ channels that pump out so repolarise and shorten the AP.
221
Purkinje cells AP through development?
Non-excitable- single AP- low frequency AP- Complex high frequency AP's
Caused by an upregulation in Kca channels (Those than open in response to Ca influx, causing bursting pattern)
222
Types of Calcium currents through development?
Early: T-current channels-Ca channels that are low voltage activated (Iva) when depolarise enter short acting compared to L-type (longer e.g. NMJ post)
Mature:
N-current channels- (hva) e.g. in terminal controls NT release
L-currents- (hva) e.g. in soma to control transcription
223
What do calcium waves do in development?
Can influence growth and differentiation e.g. Xenopus- triggers the expression of GABA
Myocyte expression of Ach R
224
Receptor type? Found?
GABA A =
GABA B=
GABA A =Ionotropic -in soma, Cl- through
GABA B= Metabotropic- axon terminal, NT release
(I before M in alphabet)
225
What is the function of GABA A channels early in development?
GABA A pump Cl- out, contributing to intracellular depolarisation, whereas in mature cl pumped in causes hyperpolarisation, switching it from excitatory to ihibitory.
And NKCC1 bringing Cl- in switches to KCC2 pumping Cl- out in mature.
(see diagram in notes)
226
How can patch clamp be used to study vision?
see when neurons fire, (e.g. Hubel and Wiesel)
| and can add fluorescent dye to see the morphology of neurons measuring
227
How can GCaMP3 be used to study vision?
GFP is stable in dim light with no calcium, but if fires in btight conformation- therefore can see when neuron populations fire e.g. where cant see individual such as simple cells.
228
Lower vertebrates have increases/decreased ability to regnerate? E.g. (3)
Increased
e. g. Newt can regenerate whole limb, muscle, bones and nerves,
e. g. xenopus tadpole tail regeneration. (BMP's trigger)
e. g. Salamander- regrow limbs and axolotl can metamorphis
229
What are the three main types of nerve injury?
Neurapraxia-mildest, produced by compression- conduction block but no physical breach of any structures.
Axonotmesis- Axon severed only or endoneurium also severed, but all other structures are preserved around.
Neurotmesis- either have epineurium only or the connective tissue is completely severed into two. (most serious)
230
Nerve injury where the Axon is severed but all other structures in tact (or endoneurium also)?
Axonotmesis
| Axon- not- mess
231
Nerve injury where there is only compression of the nerve?
Neurapraxia
| Dyspraxia may be compression on coordination neuron, least damage so not messy
232
Nerve injury where completely divided?
Neurotmesis
| Its a neuro mess
233
If endoneurium severed in nerve injury what type is this?
Axonotmesis- 3rd degree
234
If only the axon is severed in nerve injury what type is this?
Axonotmesis- 2nd degree
235
If the perineurium is severed in nerve injury what type is it?
Neurotmesis- 4th degree
236
If the epineurium is severed in nerve injury what type is it?
Neurotmesis- 5th degree
237
If only compression on the nerve in injury, what type?
Neurapraxia- 1st degree
238
If crushed periphery nerves difference if near soma proximal vs if distal?
If near soma- reorganise, whereas if distal to injury Wallerian degeneration, macrophages remove debris and myelin so schwann cells can divide and axons rebuilt.
239
What happens to the muscle if denervated? (4)
Atrophy- degeneration
AchR reverse back to embryonic- TTX resistant AP's.
More agrin receptor MUSK (muscle specific kinase) expression
BDNF nerve growth factor mRNA increased, myoD upregulated for regeneration.
240
How do peripheral nerves regenerate steps? (3)
Fragmentation (Wallerian degeneration)
Schwann cells proliferate mitosis, forming the Bands of Bugner- a schwann cell path for the nerve to follow.
Axon regrows after debris is removed by sprouting or collateral sprouting from other nerves in this path to innervate.
241
Crush injuries vs cut? which regenerates better?
Crush- basal lamina and ECM in tact
Cut- disrupt both
Crush regnerate better as ECM there still, more accurite.
242
Regeneration is better in the CNS or PNS?
PNS, poor in CNS hence cysts and glial scars can form. e.g. in spine causes paralysis.
243
Why is regeneration in the CNS poor? Evidence?
Inhibitory Oligos which when in vitro neurons avoid when regnerating.
Evidence: Removing myelin/ oligos improves regneration.
Evidence: Autoimmune to myelin proteins increases regeneration.
244
What protein in the myelin inhibits axon growth? Type?
Nogo A
245
Where are the three Nogos found?
A- oligos
B- many cells
C- muscle
246
Evidence that the Nogo inhibits regeneration? (3)
Nogo A is not present in animals that can regnerate easily e.g. salamanders.
Schwann cells in PNS lack Nogo
Anti-nogo decreases inhibition, improving regneration in SC.
247
How does Nogo inhibit regeneration?
Nogo interracts with p75 on the neuron, which would otherwise recieve neurotrophins messages to produce projections, but blocks.
248
Evidence that contradicts Nogo? (3)
No correlation between Nogo levels and regneration capcity
Much myelin is removed by macrophages after damage.
Regeneration is bad in the grey matter also in the CNS
249
As well as Nogo what other structure may be inhibitory for regeneration?
Astrocytes, they try to limit injury but create scar tissue which is v inhibitory, these are only in the CNS.
Also secrete inhibitory proteoglycan which prevents axons growing through. Can become a cyst that axons dont go through.
250
WHat are spinal cord bridges?
E.g. biological bridge over the severed nerve such as to transplant the sural nerve from the leg.
Or artifically put tube to connect two areas and the axon can grow inside. Coat in EXC and GF.
251
4 methods of transplantational treatment if tissue isnt regenerating?
1. Transplant foetal cells- if cell bodies compromised e.g. for huntingtons- graft survived but poor integration
2. Transplant Human embryonic stem cells
3. Transplant umbillical cells
4. Transplant from own body e.g. sural nerve from leg
252
Examples of adult regeneration in the brain?
Olfactor ensheathing cells- same patient so no rejection can give CNS regneration if transplanted. (sural nerve leg also used but PNS)
Songbird vocal centre, mammal hypocampus denate gyrus and subventricular zone.
253
What evokes clustering of receptors near a new synpase?
If take away muscle and sever connections thinks its making a new synapse if BM remains. why?
Agrin proteoglycan signals to NMJ.
Agrin secreted from pre, binds with MuSK Muscle specific tyrosine kinase on Post.
Signals to Rapsyn Protein -clusters of AchR
254
What are the 5 things that change on the Post as the synapse matures? (after AchR cluster)
Shape: changes to a pretzel shape
Topography: flat sheet to invaginated surface with folds
ECM: Changes to basal lamina,
Subunits: switching from Y to E as AchR matures
Partitioning: io and ligand gated channels segregate into alternating domains.
255
As synapse develops the pre synapse has which growth cone receptors? Post which TF's?
Pre: Frizzled for Wnt 7a on post
FGF R2 for FGF 22
Neurexin for Neuroligin
256
How are climbing fibre synapses refined? reorganised?
1:1 purkinje, often 4:1 at beginning before refinement.
Reorganisation: initially on soma then moved to dendrite in mature.
257
Example of reorganisation of neurons synapses as mature?
Visual systems, immature inputs not segregating if put in a radioactive tracer all over visual cortex, but over time alternating regions from different eyes.
258
If swap transmitter of a synapse in developement..?
They swab back to their preferred.
259
How can activity affect synapse formation?
Activity dependent: E.g. in order for AMPA receptors to be unsilenced need activity to NMDA receptors.
If Post recieves little excitation glutamate receptors induce the release of BDNF and Pro-NGF to p75 to apoptose.
Also, activity independent mechanisms also.
