BMS236 Building Nervous Systems Flashcards

Question

What is BMP?

Answer 1

A protein that will cause a cascade that will cause the differentiation of cells into skin ectoderm - It has been conserved through time and evolution

Answer 2

An antagonist to BMP (inhibits BMP signalling)

Answer 3

BMP signalling is inhibited by chordin

Answer 4

``` BMP = dpp Chordin = sog ``` So sog inhibits DPP causing the cells to become the neurogenic region

Answer 5

Chordin and BMP diffuse from opposite ends so where they meet is where the neural tube develops

Answer 6

- BMP binds to BMP receptor and a secondary signal (Smad) is phosphorylated - Smad can then up regulate transcription factors like Msx1, GATA1 which leads to epidermal differentiation

Answer 7

- BMP inhibited - No Smad phosphorylated so different transcription factors are up regulated (xlpou2, soxd) - Neural differentiation pathway

Answer 8

When the neural plate rolls up to form the neural tube

Answer 9

A specialised part of the mesoderm that expresses transcriptional factors (Gsc) expressing antagonists of BMP eg. chordin which diffuse into the ectoderm and bind with BMP - Forming neural plate in ectoderm neighbouring the organiser

Answer 10

Low levels of the nodal protein leads to ventral mesoderm | High levels gives the organiser

Answer 11

- Differentiate into anterior endoderm, prechordal mesoderm and notochord - It involutes, intercalates and undergoes convergent extension - Forms the midline of the neural plate

Answer 12

- A donor organiser was grafted from a donor onto a host newt - found that a 'twinned' embryo developed with a secondary neural axis - Secondary neural tube was host derived showing it was induced from the ectoderm in response to signals from the organiser - The prechordal mesoderm ad notochord where donor derived showing they're formed from the organiser

Answer 13

Extracted all mRNA from organiser cells and reverse transcribed them to cDNA. This was tested to look for a protein that would mimic the organisers ability to induce a secondary neural plate

Answer 14

Cut out the node and culture | It develops into a long rod shape which is the notochord and at the anterior end the prechordal mesoderm develops

Answer 15

The idea that neural inducing molecules such as BMP inhibitors (Chordin) and ant antagonists only remain in the prechordal mesoderm (part of organiser that is involuted first) not all of it. the later part of the node expresses Wnt, FGF and retanoic acid which posterialises anterior tissue

Answer 16

BMP and Wnt antagonists

Answer 17

Want, FGF and retanoic acid - promise posteriorisation and growth

Answer 18

having 2 antagonist molecules at each end of a forming structure

Answer 19

- Alan turing reaction diffusion model | - Lewis Wolpert's French flag model

Answer 20

The idea that different levels of a morphogen concentration leads to a different cell fate

Answer 21

A diffusible molecule that causes a particular response from a cell depending on its concentration gradient

Answer 22

- Control segmentation and specify A P | - Massively conserved through time

Answer 23

Retanoic acid gradient - high concs lead to neck - low concs to tail

Answer 24

A specialised border that develops at the neural - ectoderm boundary (edge of the neural plate)

Answer 25

- Neural cress formation | - Roof plate formation and dorsal neural tube differentiation

Answer 26

The neural crest

Answer 27

- Border is established between neural plate and surface ectoderm which expresses transcription factors such as msx - induce at intermediates levels of BMP signalling - Wnts, FGFs act together with msx1 - these transcription factors characterise neural plate border cell - Wnt signals act together wot NPB transcription factors to up regulate more transcription factors (c-Myc, Id, Snail) that characterise neural crest cells - Neural crest cell transplantation factors up regulate a further set of genes that promote epithelial mesenchymal cell transition. - Neural crest cells delaminate from the border and migrate

Answer 28

Intermediate levels of BMP signalling triggering transcription factors (msx)

Answer 29

( c - MYC, Id, Sox9) Role in formation of neural crest cells They activate genes that control proliferation

Answer 30

Because it gives rise to high number of different types of cell - Peripheral nervous sytem - Facial cartilage - Schwann cells - dentine of teeth - Enteric nervous system

Answer 31

- Partially by how genes - time of generation of neural crest cells - Migratory pathway - encounter different signals

Answer 32

A few are retained at the border and form roof plate cells - it is not clear why some cells are retained are and others aren't

Answer 33

Important in the final step of neurulation and in dorsal neural tube patterning

Answer 34

- Roof plate cells up regulated BMPs and Wnts - Secreted and diffuse into dorsal tube - Indice expression of transcription factors (Pax6, Pac7, Pax3, Lim1) that cause neural tube progenitors to acquire dorsal identities

Answer 35

- It was thought that they act as morphogens | - But recent work shows that roof plates may express many different BMP's which induce a particular dorsal cell type

Answer 36

Roof plate cells, neural crest cells, different classes of dorsal sensory relay interneurones

Answer 37

Norochord | Floor plate cells located at the ventral midline

Answer 38

- Ectopically implanting a donor notochord which induced an ectopic floor plate and saw it induced ventral neurones such as motor neurones

Answer 39

The notochord

Answer 40

Hedgehog gene

Answer 41

shh mRNA | - Only gets upregulated when notochord formed

Answer 42

Made and secreted from floor plate diffuses into neighbouring cells and establishes a concentration gradient resulting in ventralisation due to the induction of expression of transcription factors

Answer 43

Secondary neural plate and notochord

Answer 44

A high concentration of shh protein induces floor plate which unregulated shh gene leading to more shh protein

Answer 45

shh acts at early stage to confer a DV pattern of transcription factor on progenitor cells

Answer 46

The opposing gradients of BMP and shh - act antagonistically to each other shh does not act at the same early stages of BMP

Answer 47

- Notochord secretes shh - shh diffuses through spinal cord - conc gradient (morphogen) - It induces different patterns of transcription factors - High concs of shh cause floor plate cells to develop which occupy ventral midline of neural tube - activates shh - shh mRNA in both notochord and floor plate - shh diffuses into neighbouring cells causing ventral fate

Answer 48

Knowing how processes work and how the nervous system forms allows us to push embryonic stem cells towards a defined fate which can be used in new drugs

Answer 49

Neural stem cells

Answer 50

- During early development, some cells continue to span the width of the neural tube - Their nuclei migrate back/fourth at different stages in mitotic cycle - These are radial glia

Answer 51

Neural stem cells maintain a luminal contact and over time cell bodies come to occupy ventricular zone (ependymal zone) - depending on the plane of diffusion they can give rise to two radial glia and proliferating daughter progenitor - Proliferating progenitors move into the adjacent mantle zone and differentiated cells moves away into the outer marginal zone

Answer 52

Wild type drosophila - Have cells that have proneural genes so are able to come neurones Proneural mutant - No cells become neurones Neurogenic mutant (notch-/-) - But in a neurogenic mutant more neurones are formed Shows Notch required to prevent a cell becoming a neurone - acts locally on immediately to adjacent cells

Answer 53

Involves transmission of an inhibitory signal between a pair or cluster of cells to prevent cells that receive the signal from adopting a specific fate When the central cell in the pro neural cluster inhibits the surrounding cells and stops from becoming neuroblast

Answer 54

- Cells express both Notch and Delta equally - One cell starts to express more delta - Other cells increase in notch in order to receive the amount of delta - The increase in notch causes the inhibition of delta in those cells - The difference in notch and delta increases leading to a neuroblast (with high delta) and epidermis (with high notch) => Lateral inhibition

Answer 55

Yes the proneural glosser is an equivalence group | Notch -/- or Delta -/- causes all cells to become neuroblast - must be competent

Answer 56

Groups of cells in the neurectoderm | One cell in the cluster will become a neuroblast and the others will become epidermis

Answer 57

They have a certain shape Exist as radial glia (neural stem cells) Provide a pool of undifferentiated cells that are used to build yo the nervous system over time in embryogenesis

Answer 58

Primary motor cortex

Answer 59

Spinal cord

Answer 60

Projects directly to spinal cord via corticospinal tract | Regulates the motor tracts that originate in brainstem

Answer 61

Lateral descending system controls distal limbs is important for goal directed movements of hand and arms

Answer 62

Contains neuronal circuits that mediate reflexes autonomous such as walking

Answer 63

One sensory neurone and one motor neurone | - Simplest reflex

Answer 64

Many neurones and interneurones

Answer 65

No big movements at most twitches

Answer 66

- Monitor commands going down to muscles to make sure they are appropriate for the situation the person is in - If commands are inappropriate then they calculate correction signals which they send back up to motor cortex for approval

Answer 67

Acts as a feedback loop and sends info back to primary motor cortex - Helps initiate and terminate movements and establish a normal level of muscle tone

Answer 68

Mainly feedback to motor cortex but can also send its error correcting signals straight down to the brainstem

Answer 69

Different areas of the brain were electrically stimulated and 'Brodmann's area' found to be the area that elected the most movement with the lowest intensity - Primary motor cortex

Answer 70

Hands fingers face - for fine movement

Answer 71

Carry motor commands down through the brain, brainstem and to the spinal cord Involved in planning initiating and directing movements Output to lower motor neurones via interneurones

Answer 72

Ancient motor centres of the brain stem - Vestibular nuclei - Superior colliculus - Recticular formation

Answer 73

Direct and indirect motor pathways

Answer 74

Input to lower motor neurones from axons extending directly from cerebral cortex

Answer 75

Input to lower motor neurones from basal ganglia, cerebellum and cortex

Answer 76

Leads to muscle contraction from lower motor neurones

Answer 77

Causate, putamen, substantia nigra, sub thalamic nuclei

Answer 78

Causes twitching, face movements, uncontrolled swearing (rare) and unable to terminate movements - Caused by problem with basal ganglia

Answer 79

via the thalamus and brainstem

Answer 80

Excitation of muscle by alpha - motor neurones Continuous info from each muscle at each isntant - Muscle length - Muscle tension and rate of change of muscle tension development - Lots of info relayed from these receptors to spinal cord

Answer 81

Send muscle length information to the spinal cord and cerebellum

Answer 82

Intrafusial are inside the spindle and extrafusial are outside the spindle Don't actually contribute to muscle tension Purely sensory role

Answer 83

Wraps around equator of dynamic bag, static bag fibres and long and short chain fibres

Answer 84

innervate bag fibres and short chain fibres innervate bag fibres and short chain fibres in order to change they length and mechanical properties

Answer 85

Wrapped around the equator of both bag and nuclear chain intrafusial fibres Pulling apart these cooked initiates an action potential on the axon

Answer 86

I - dynamic stretches - sensory endings relay information on the ‘dynamic’ phase of muscle stretch ie. as stretch is occurring II - Static stretches - sensory endings relay information on the static phase of muscle stretch ie. its final length

Answer 87

- Extrafusal fibres shorten around the spindles - loses tension - gamma motor neurones are coactivated with alpha motor neurones to ensure that the spindle shortens with the extrafusal fibres in order to maintain tension

Answer 88

Because there are 635 muscle - it would cause a sensory overload

Answer 89

- Serotonin increases gamma motor neurone activity ( action potential firing) - this causes intrafusal fibres can be slightly stiffer - stiffer materials transmit stretches with a greater fidelity - Noradrenaline decreases gamma motor neurone activity - causing intrafusal fibres to be more elastic and floppy - elastic materials don't transmit stretches well

Answer 90

- Muscle stretched by hammer blow to its tendon - Primary sensory endings are activated and sends action potentials along the limb to the spinal cord - Muscle contracts in opposition to the stretch and the limb jerks as a consequence

Answer 91

(putting hands together and pull) - causes excitation in upper segments of spinal cord - Excitation spills over to rest of spinal cord - causes leg twitch to increase as more motor units are involved

Answer 92

- Group II afferents fire at about 50Hz when arm is straight - Group III afferent fire at about 20Hz when fully flexed - Vibrator applied to tendon drives the group II afferents in muscle so they discharge at 100Hz - This makes the arm shorten as the brain must think it is really seethed as 50Hz is straight

Answer 93

Polysynaptic reflex - Spindle Ia makes excitatory connections on homonymous muscle (muscle the spindle is in) and are synergistic muscles (those that help the main muscle contraction) - Ia's also act through inhibitory interneurones that innervate antagonistic muscles - When muscle is stretched the Ia firing rate increases - This cause contraction f the homonymous muscle and relaxation of antagonistic muscle - Reflex counteracts the stretch enhancing the springiness of the muscle

Answer 94

Spinal cord and somatosensory cortex

Answer 95

Medial - lemniscal system

Answer 96

1. Central processes of dorsal root ganglia cells synapse on neurones in gracile and cuneate nuclei in lower medulla 2. Axons from these nuclei ascend in medial lemniscus and synapse on neurones in ventral posterior lateral nucleus of thalamus 3. Neurones of lateral nucleus send axons to primary somatosensory cortex.

Answer 97

Primary (s1) The anterior parietal lobe and the posterior parietal cortex Secondary (s11) Deep within lateral sulcus

Answer 98

Proprioceptive defects (ability to discriminate size, texture and shape)

Answer 99

Food Predators Mates

Answer 100

The optic nerve cat transmit all the information that is received by the retina as there is a limit to the thickness of it. So the retina also has to decide what is transmitted

Answer 101

Image acquisition

Answer 102

``` Ventral stream - V1 cortex to inferior temporal cortex - Processes object identity Dorsal stream - V1 cortex to posterior parietal - Spatial location ```

Answer 103

Regulate the amount of light

Answer 104

Focuses image on fovea

Answer 105

Fovea is part of the retina with the highest visual acuity | - Rest of the retina has Lowe acuity and contains primarily rods

Answer 106

Cells in the retina that light has to travel through before getting to the photoreceptors

Answer 107

Interneurons between the layers of the retina

Answer 108

- Photoreceptors (rods and 3 types of cones) - Bipolar cells - Ganglion cells

Answer 109

Inhibitory - inhibit bipolar cells and feed forward to ganglion cells - mostly gabaergic or gycinergic Most diverse type of cell in retina (25 types) - showing importance of their function Also have gap junctions between bipolar and ganglion cells

Answer 110

Inhibit photoreceptors nd feed forward to bipolar cells

Answer 111

Rod - dim | Cone - active and bright - colour

Answer 112

rod - more disc and molecules because they need to be stimulated by smaller amounts of light

Answer 113

In darkness - Na+ and K+ channels open so the membrane is depolarised - Activated by cGMP in the cytoplasm - keeping them open In light - ligand gated g coupled receptor is activated and the G protein breaks down into alpha and gamma subunits - activates phosphodiesterase - decreases cGMP in cytoplasm causing the Na+ K+ channel to close - hyper polarisation of photoreceptor

Answer 114

In retina | Constantly release glutamate - happens in darkness

Answer 115

On cells - depolarise who light goes on them | Off cells - hyper polarise when light

Answer 116

Photoreceptors hyperpolarise in response to light so less glutamate and less activation of off bipolar cells

Answer 117

They don't express ionotropic glutamate receptors (channel) like off cells They express metabotropic glutamate receptors which are g coupled receptors When metabotropic receptors are activated cGMP drops down in cytoplasm closing Na+ K+ channel - Hyper polarisation If less glutamate, less activation of metabotropic channels then depolarisation

Answer 118

Ionotropic - Are channels Metabotropic - G coupled

Answer 119

An area of the retina which when illuminated activate a visual neurones

Answer 120

Stimulation of the centre of bipolar cells leads to depolarisation and the stimulation of the periphery is of opposite polarity (hyper polarises)

Answer 121

When stimulate centre of receptive field, that photoreceptor hyper polarises. It is directly synapsed with the bipolar cell so that also hyper polarises When stimulate the periphery, those photoreceptors hyper polarise but they are synapses with horizontal cells - these hyper polarise which steps the hypopolarisating of photoreceptor which depolarises bipolar cells

Answer 122

Illumination of the whole receptive field does not activate ganglion cells it appears that ganglion cells are designed to respond to differences in illumination that occur within the receptive field

Answer 123

Paracellular - 80% | Magnocellular - 10%

Answer 124

``` Paracellular - Smaller with smaller dendrites - More densely packs - detect fine spatial details better - smaller receptive fields - Sustained response - Detects form/colour Magnocellular - Motion detection - High conduction velocity - More sensitive to light ```

Answer 125

Two extreme hypothesis: Weiss (1928) - Resonance theory - stochastic and diffuse neuronal outgrowth occurs to all targets followed by elimination of non functional connections Sperry (1939) - Chemoaffinity hypothesis - Directed and specific outgrowth occurs through axons following "individual identification tags" carried by the "cells and fibers" of the embryo

Answer 126

Sperry first did experiments in newts and then moved to frogs - he cut the optic nerve and removed the temporal retina (allow just nasal axons to grow back) - The axons grew back directly to the right place meaning sperry was right

Answer 127

If Weiss were right, would expect to see random patterns of axons in embryos. In fact see that patterns of axon outgrowth are highly organised, reproducible and stereotyped

Answer 128

- Early stage embryo - Cut and replace segment of neural tube before motor axons grow out - Despite displacement, motor axons still found way to their correct target - Suggests axon guidance

Answer 129

Factors in the cells environment that axons use to find their correct target

Answer 130

The growing tip of the axon which Cajal proposed sensed cues in the environment

Answer 131

- Relatively simple nervous systems - Embryos easy to observe and manipulate - In the large insects, individual cells could be ablated using lasers

Answer 132

Detailed analysis resulted I the identification of almost every neuron in the embryonic nerve cord allowing a map of axon predictions to be made

Answer 133

- Cells were ablated that were thought to be carrying potential cues - this caused the axon to stop at the axon where it would usually turn as the cue was not present - Shows evidence for growth cone and that axons can be directed in response to other axons

Answer 134

- Axons can selectively fasciculate with other axons - Axon surface carry labels or cues - Different growth cones express different sets of receptors for such cues - Early axons (pioneers) form an axon scaffold on which later axons extend - Established axon surfaces as one potential source of guidance cues

Answer 135

- Ghosh and Shatz (1993) Visual cortex - Ablated sybplate neurones from one area and innervation of lateral geniculate nucleus failed in that area - Evidence for scaffold

Answer 136

Growth cones appear to react at specific points - For example, in the grasshopper embryo limb, the pioneer Ti1 (tibial1) growth cone makes a specific turn at the limb boundary, and then again as it approaches a specific cell, Cx1. -Ablation of Cx1 causes the Ti1 growth cone to stall at the other side of the limb boundary. - Neither Cx1 nor the limb boundary cells are distinguished by any obvious morphological features. Cx1 and the other cells are sometimes referred to as ‘stepping stones’ or ‘guidepost cells’ Implies that there must be molecular differences in the environment

Answer 137

Central - Microtubules Transitional - f actin Peripheral - both

Answer 138

In peripheral domain - The actin bundles are cross linked int a net - Highly motile

Answer 139

In peripheral domain - The actin bundles are polarised to form larger bundles - Highly motile

Answer 140

Tubulin is dragged sporadically into the filopodia | Happens much more dramatically when the growth cone comes into contact with an attractive cue

Answer 141

They reorganise - F actin treadmilling slows and f actin accumulates - This stabilises the filopodium and drags microtubules into the back of the filopodium

Answer 142

When encountered a promoting cue - Molecular clutch is engaged and reward actin treadmilling slows - results in forward movement of the filopodium - Actomyosin based actin tubules link pulls microtubules into the wake of extending filopodium

Answer 143

Attachment of the growth cone to a substrate is not enough to drive forward movement, need stimulus of cue to rearrange cytoskeleton.

Answer 144

Mixtures of neurone in culture were found to fasciculate only with their own kind watching real growth cones showed that they were repulsed by each others axons and that contact led to their collapse

Answer 145

Destabilises f actin - the opposite effect of an attractive cue

Answer 146

Treatment whir EphB1 protein - Normally would have full growth cone collapse - Would have localised collapse of filopodia contributing to growth cone reorganisation

Answer 147

A family of inhibitory guidance cues | - Cause growth cones to turn

Answer 148

Biochemical purification of the factor from the retina responsible for causing the collapse of sensory axons

Answer 149

Membrane bound | Secreted

Answer 150

Contact attraction Contact repulsion Chemoattraction Chemorepulsion

Answer 151

Components that axons can attach and grow from

Answer 152

No simple relationship | e.g. collagen is better than laminin for adhesion but laminin is better than collagen for outgrowth

Answer 153

Laminin, a growth-promoting extracellular matrix protein, is localised in the optic nerve Blockade of the receptors for laminin slows down the growth of retinal axons, but does not change their direction Gradients of laminin in vitro do not direct axon growth.

Answer 154

Permissive substrates - Contact attractants Non permissive factors - contact repellents Axon growth is a balance between permissive and non permissive factors

Answer 155

Non permissive factors used in early patterning and to guide axons - detected by receptor called ephs

Answer 156

Ephs and ephrins cause repulsion between cells Early on, this helps to compartmentalise the embryo into discrete domains - used t keep axons out of specific places

Answer 157

A secreted protein similar to laminin which can associate with the extracellular matrix (in floor plate) - Can turn commissural axons

Answer 158

They reprogram | - Lose responsiveness to netrins once crossed midline

Answer 159

- Hydrophobic end - Can use them to trace axons, lineage and membrane trafficking - Dil is an example

Answer 160

Experiment - On one side of the rodent hindbrain an ectopic floor plate is added so the commissural axons on that side sill have to cross it before the endogenous floor plate but other side doesn't it In the hindbrain - axons exposed to ectopic floor plate before reaching midline turned - Axons exposed to ectopic floor plate after crossing midline did not respond

Answer 161

They become sensitive to them - Semaphotins and porteins called slit in the floor plate which repel them - Also expressed in spinal cord - creating a channel for axons to grow though

Answer 162

As in the vertebrate floor plate, insect midline glial cells express diffusible attractants (netrins) and cell surface repellants (slits). Levels of these determine

Answer 163

Roundabout gene, Robo, encodes a receptor for the inhibitory protein Slit. Robo protein is expressed at high levels on axons that don’t cross the midline. Commissural axons initially express low levels but high levels after they cross.

Answer 164

Roundabout gene, Robo

Answer 165

In Robo mutants (no Robo protein made), Slit is no longer detected, so all axons go back and forth across the midline forming Roundabouts of axons When Comm protein is missing (Comm mutant), Robo protein is expressed at hi levels in those cells that would normally cross the midline, and which now extend their axons longitudinally

Answer 166

Comm is expressed only in those neurons that normally cross the midline and is switched off after they cross.

Answer 167

If Comm’s expression is forced in all neurons, Robo protein is lost everywhere resulting in a phenotype just like the Robo mutant. ie Comm controls Robo

Answer 168

Comm encodes a “trafficking” protein that prevents Robo protein from reaching the cell surface so that the growth cone cannot receive Slit inhibitory signals before X-ing

Answer 169

There is no comm homolog Robo homolog - Robo1 - expressed before and after crossing midline - Rig1 - expressed only in pre crossing fibres and appears to block Robo1 signalling until the midline is crossed

Answer 170

How axons stay and get off the axons scaffold - Involves homophillic binding by cell adhesion molecules - e.g.. Fasciclin II

Answer 171

Homophilic (like binds to like) interactions can bind two cell surfaces together

Answer 172

May defasciculated axons

Answer 173

Novel fasciculations

Answer 174

Interfere with adhesion by proteins that block e.g. BEAT Regulates FasII

Answer 175

- Discrete targets | - Topographic maps

Answer 176

In Grasshopper and Drosophila, ablation of specific target muscles (by ablation of muscle precursor cells) leads to failure of relevant motor axons to leave main motor trunk at appropriate branch points Suggests that axons are “looking” for specific “labels” on their targets

Answer 177

the axons wander and do not make synapses (even though the muscle is there)

Answer 178

leads to axons innervating the wrong muscles

Answer 179

The adhesion molecule Fas3 is expressed in specific muscles and in the motor axons that normally innervate them

Answer 180

leads Fas3-expressing axons to innervate new targets

Answer 181

Neighbouring neurons send axons to neighbouring sites in their target to maintain the topology (order) in the target Two possibilities how: - Each axon has a unique label complementary to a unique label in the target - That a co-ordinate system, encoded by gradients of signalling molecules, stamps a "latitude and longitude" onto cells of the target. This would be read by complementary gradients of receptors expressed in the retinal ganglion cells.

Answer 182

Helps in object recognition

Answer 183

Red Green Blue Activate different types of bipolar cells

Answer 184

Green - top Blue - bottom Light from the top (blue sky) activates bottom of the retina and light from bottom (green grass) activates the top

Answer 185

Regulation of saccadic movements Receives inputs from ganglion cells, auditory system, somatosensory system Integrates information from different sensory modalities

Answer 186

organisation whereby neighboring cells in the retina feed information to neighboring places in their target structures (LGN, SC, cortex)

Answer 187

Retinotopic organisation

Answer 188

LGN preprocesses the visual information

Answer 189

6 layers Monocular input Layers alternate input from each eye P and M ganglion cells remain segregated Organised retinotopically Ganglion cell axons make 1:1 connections with LGN projection neurons

Answer 190

Receptive fields of LGN neurons are similar to the receptive fields of retinal ganglion cells

Answer 191

Important to process retina information

Answer 192

Subject looks at an image of a particular object. Few neurons in higher cortical areas fire Stimulation of the same neurons causes perception of the same object

Answer 193

Recognise objects in an orientation not seen before Recognise no matter what size Effortless recognition of previously unseen objects

Answer 194

Detection of edges --> Detection of combination of edges and contours --> Detection of object parts ---> Detection of objects from one point of view ---> View invariant object detection --> categorisation Each level is reached as the complexity of the stimulus increases

Answer 195

Increase in complexity of responses of neurons along the ventral stream Increase in the receptive field size of neurons along the ventral

Answer 196

- Layering | - Columns (ocular dominance, orientation, direction and blobs)

Answer 197

Different layers receive inputs from different parts of the brain Interneurons process this information - input between layers in the same cortex

Answer 198

Ocular dominance column Orientation (direction) columns Blobs (colour)

Answer 199

Inject radioactive glucose in cortex and stimulate one eye with light Shows that each column receives inputs from either ipsilateral or contralateral eye

Answer 200

When all three types of columns come together

Answer 201

Simple Complex Hypercomplex

Answer 202

Hubel snd Weissel

Answer 203

When shined a light on centre of the receptive field - cells respond Surrounding cells - respond on the dark - showing it has an inhibitory surround - Change orientation of the bar and no response - They concluded that ganglion cells were in a line down the middle

Answer 204

Differs from simple cell because responds to bar of light anywhere in the receptive field Changes the orientation of the bar - cell doesn't respond

Answer 205

Repsonds to bar of light anywhere in receptive field If part of the bar is not over the receptive field then no response If change the orientation of the part of the bar not over the receptive field then spikes again

Answer 206

Guessing | Computational models

Answer 207

``` Record from a visual neuron Apply thousands of images Identify those that evoked spikes Average them or Build a computational model that predicts responses to all of the images ```

Answer 208

Generate many images with defined geometrical properties (size, orientation, curvature, spatial frequency etc.) Define orientation-, curvature-, frequency sensitivity or Make an educated guess of what should visual neuron respond to

Answer 209

That cells in V2 cortex reposted to more complex stimuli then V1 - gets more complex

Answer 210

Full face - cells respond Partial face - not as many cells raspond When characteristic features of a face are removed (e.g.. eyes, mouth, face shape) neurones don't respond - Neurones dont respond steadily - start to adapt

Answer 211

A specific neurone is fired when saw pictures of Jennifer anniston - Could be at any scale and orientation - same response Didn't with other neurones

Answer 212

Psychophysical methods and illusions Lesions and other ways to silence neurons or parts of the brain Anatomical studies and morphology (to study connections between neurons) fMRI, electrophysiological recordings and imaging Modeling and theoretical simulations

Answer 213

Humans - ethics, can get verbal feedback Primates - ethics, similar model to humans Lower mammals (cats, rodents) - Key organisation of the brain is the same Lower vertebrates (zebrafish) - Brain different to humans, transparent embryo Invertebrates (Drosophila) - not good to compare to humans

Answer 214

Investigate adaptation - Illusions with colour - Three pictures - George Bush and Barak Oboma

Answer 215

- Lesions - removing part of the brain and look at the damage or new behaviour - Whole brain imaging techniques - - Multi-electrode recordings in different brain areas

Answer 216

Directed (animal models) - can't get feedback from them | After strokes and other neurodegenerative diseases

Answer 217

Functional magnetic resonance imaging

Answer 218

Active neurones use a lot of oxygen and glucose - you can then see which parts of the brain uses these using functional magnetic resonance imaging - Get a human subject and look at the images of the brain when looking at moving lights and stationary lights - Can see cortex is much more active in movement showing its importance in perceiving motion

Answer 219

Fluorescence proteins - Drive the expression of proteins in specific neurone subtypes so difference can be highlighted Viruses - Label one cell and pre synaptic neurones - can look at the circuitry - as the viruses will pass through the synapse as well

Answer 220

Can be used in vivo | - Meaning it will have a sensory input as slices that have been cut out will have lost its innervation

Answer 221

In vivo Slices Cultured neurones (only for molecular mechanisms)

Answer 222

Enhancer traps

Answer 223

Record activity of cell and neurones | Image the activity of a large population of neurones simultaneously

Answer 224

Patch clamp method

Answer 225

GCaMP3 - Reports changes in neuronal calcium activity and therefore neuronal activity - Brightness occurs when Intracellular Ca2+ is high - By observing changes in brightness you can there foe feel when the neurone is active and how much is active

Answer 226

Recording the activity of many neurons Can record simultaneously the input and the output of a particular neuron (circuit reconstruction) One can easily target particular neuronal types(e.g. Glu-ergic and GABA-ergic)

Answer 227

Cant image as fast as electrophysiology | - Cant detect high frequency spikes

Answer 228

- Opens when yellow light - Na+ enters - Depolarisation of neurone occurs - spikes

Answer 229

- Cl- channel - Hyperpolarises with yellow light - doesn't spike - Depolarised with blue light - spikes

Answer 230

Most abundant cause of blindness - No treatments - Caused by death of photoreceptors

Answer 231

Try to use an artificial retina - But what part of the brain needs to be active as there are no photoreceptors - What method would you use to activate it

Answer 232

``` Retina (mostly for retinitis pigmentosa) Visual cortex (when the optic nerve didn’t develop or is destroyed) ```

Answer 233

Retina performs complex computations Different ganglion cells have different functions and project to different brain areas Stimulation of retinal ganglion cells with simple stimuli is useless (e.g. motion sensitive RGC is active only when there is motion)

Answer 234

- Electrical stimulation | - Channel rhodopsin and halorhodopsin

Answer 235

Accessing bipolar cells or photoreceptors is difficult because ganglion layer is above so only accessible by electrode

Answer 236

A family of growth factors in the nervous system

Answer 237

Remove or add limb buds in chick embryo | - More/less innervation so more/less dorsal root ganglion neurones surviving

Answer 238

Implies that limbs being innervated is giving an advantage for the organisms survival

Answer 239

Trophism - relating to food or nutrition | Tropism - Meaning turning

Answer 240

He reasoned that fast growing muscle like cells might secrete survival factors (limb buds are fast growing) - He therefore implanted sarcomas (tumours) into embryos - It caused an increase in the size of dorsal root ganglion - Provoked selective survival of non placodal sensory and sympathetic neurones

Answer 241

Demonstrated presence of diffusible growth factor - Purified from snakes venom and mouse submaxillary gland - Found antibodies to the purified growth factor that could block dorsal root ganglion growth in vivo and in vitro

Answer 242

``` Activated from submaxillary gland Has subunits - alpha, beta, gamma Beta subunit - Dimer - Active component - alpha and gamma subunits only found in submax - storage ```

Answer 243

In a partition chamber - DRG in centre - nerves grow out into outside chambers if NGF present in any chamber - If NGF only present in centre compartment then no outgrow - If NGF taken away from the axons that have outgrown then they die

Answer 244

Responsible for survival of axons - when taken away from experiment they die Can also guide axons in vitro

Answer 245

``` TrkA - high affinity - it is a classic RTK (kinase) - they dimerise and phosphorylate - affects differentiation and growth P75 - NTR - low affinity - Promote cell death ```

Answer 246

Because there are low levels of them in the nervous system

Answer 247

Control whether or not cell death is occurring

Answer 248

No - Placodal sensory ganglia e.g. nodose prefer BDNF over NT-3 - Crest- derived DRGs have subpopulations that respond to NGF, BDNF or NT3 - Sympathetics respond to NGF or NT3 but not BDNF

Answer 249

Yes neurones may have no dependancy

Answer 250

NT3 can support many neurone types early in development eg. on the way to targets Arrival at the target often coincides with new expression of neurotropin by target

Answer 251

need BDNF and NT3 early then NGF then NGF or MSP

Answer 252

``` Dropsophilla and c.elegans - Other families Glia - derived neurotrophic factors e.g. GDNF supports midbrain dopaminergic neurons - Cytokines e.g. ciliary neurotrophic factor CNTF hepatocyte GF macrophage-stimulating protein (MSP) - Testosterone effects on motorneuron pools accounting for sex differences ```

Answer 253

Motor neurones innervating the triceps and pectoral muscles develop monosynaptic connections directly with PNS, whereas motor neurones innervating the cutaneous maximus (CM) and latissimus dorsi (LD) receive polysynaptic input from interneurons (IN). Controlled by a neurotrophin secreted from CM and LD, which turns on the transcription factor (TF) Pea3 in the MNs.

Answer 254

Everywhere in the nervous system

Answer 255

Because neurones are refining | - Relationship between the size of the target and how many neurones are required

Answer 256

``` Somatosensory barrels - whiskers on rodents - In CNS cortex - refined Auditory system - refined - doesn't follow the correlation of size and neurones required - shows that other inputs are involved ```

Answer 257

Apoptosis - programmed cell death

Answer 258

It is inhibited by actinomycin D or cycloheximide

Answer 259

Macrophages

Answer 260

DNA damage and p53 activation (tumour suppressor) ---> Activation of mitochondria/ cytochrome c ----> activates initiator caspase 9 ---> Effector cascade 3 ----> Apoptosis

Answer 261

Death ligands ---> activates death receptors ---> activated initiator caspase 8 ---> Effector cascade 3 ----> Apoptosis

Answer 262

Enter the apoptosis pathway and activate apoptosis | Balance of the signals determine whether a cell lives or dies

Answer 263

C.elegans - Knockout of Ced3 and Ced4 - Cells lived that weren't suppose to - Showing these pro apoptotic signals are required for cell death

Answer 264

That the target secretes a neurotrophic factor rewind for the presynaptic neurone to survive

Answer 265

Nerve growth factor (NGF - a type of neurotrophin) - Deprived from sympathetic ganglion neurone in vitro - SGNs have p75NTR, TRKA receptors - Blocking NGF triggered apoptosis as the receptor for NGF is TRKA which is present - Also shown in knockout mice in vivo

Answer 266

Adding anti-p75NTR blockers - p75NTR is the other receptor present on the sympathetic nerve ganglion so even though TRKA isn't activated by NGF, the other receptor stops the trigger of apoptosis

Answer 267

They provide pro and anti apoptotic signals | - An individual neurone needs both the correct neurotrophins and the absence of the wrong neurotrophins to survive

Answer 268

Pro NGF strongly activates p75NTR receptor which leads to apoptosis - Levels of enzymes that cleave proneurotrophins are important - growth cones can release these enzymes

Answer 269

ProBDNF is synthesis - binds to carboxypeptide E - Leads to secretion - triggered by depolarisation or ligand binding - Cleaved to make proper form and release to axons

Answer 270

Want to end with one axon innervating one muscle fibre but start with much more - muscle fibre produces proBDNF which acts as a repellant - the 'winner' axon converts proBDNF into BDNF allowing it to survive - the 'loser' axon does not convert it - triggers retraction - if no other neuromuscular junction then apoptosis is triggered

Answer 271

Not all neurones make synapses - outcompeted | Synapse formation can dictate neuronal or target surivial

Answer 272

Correct receptor being expressed Synapse at the correct location Correct part of the membrane to differentiate unto synapse Receptors to make the target the tissue The correct number of synapses made this can vary from 1 to 10000 per neuron

Answer 273

Motor axon differentiates to motor nerve terminal at contact point Contact point is dictated by gap junctions made by Schwann cells - redistricts where the junction can occur Muscle forms the post - synaptic apparatus

Answer 274

- Small vesicles at presynaptic membrane - Narrow cleft between pre and post synaptic membranes - fill with special proteins - Post synaptic membrane apparels thickened

Answer 275

It was in vivo - so cant see what happens at the very early stages

Answer 276

- Filopodia retraction - tight junction formation - Membrane and cell gycloproteins are added - Presynaptic vesicles, dense ECM and receptors accumulate at the cleft

Answer 277

When axons reach targets - highly variable

Answer 278

Cat visual cortex | - Synapse density increased for one month after birth

Answer 279

Site availability may be restricted - Astrocytes may cover cell body but dendrites are free Post synaptic cells may have pre-prepared sites

Answer 280

Adhesion proteins | - Immunoglobulin domains that stick them together

Answer 281

e.g. Initially ACh receptors are present at moderate levels on myotubule surface Innervated by AChRs cluster in post synaptic membrane The clustering involves both redistribution of AChR proteins and localised synaptic synthesis of AChRs Aggregation of neurotransmitter receptors is the principle feature of synaptogensis

Answer 282

Glycine, GABA, Glutamate

Answer 283

Denatured and destroyed muscle to break neuromuscular junctions - MMuscles regenerate and clustering occurs again - Must be something in the basal lamina causing this - The proteoglycan Agrin was discovered

Answer 284

Made in nerves and moves to basal lamia

Answer 285

Z+ agrin is released from the axon - has a high affinity for MuSK (a kinase) - Agrin binds to MuSK protein and signals Raspyn - Raspy clusters which have Ach receptors - end up with lots of Act receptors clustered

Answer 286

They are insensitive to agrin

Answer 287

Junction changes from a simple oval plaque to a pretzel like set of branches

Answer 288

Junctional membrane changes from a flat sheet to invaginated surface with gutters and folds - receptors cluster at the top

Answer 289

Changes to basal lamina over the ACh rich | membrane and cytoskeleton under it

Answer 290

Composition of AchR subunit changes

Answer 291

Ion and ligand gated channels segregate into discrete alternating domains

Answer 292

The growth cone has the receptors and the cell the ligands - Growth cone - frizzled receptors - Granule cells - express Wnt7a Contact recruits vesicles and synaptic proteins to form presynaptic site

Answer 293

Initially interact with lots of cells which is refined Ina. mature cerebellum there is 1 climbing fibre per purine cell In development, typically up to 4 climbing fibres per day

Answer 294

Synapse refinement is required to ensure the right number of synapses and that they are focused Connection focusing - Immature inputs are not segregated - eg. Reorganise so cortex receives info from different parts Transmitter choice - Choice may be due to environment - Not all hard wired in

Answer 295

Acquisition of presynaptic release machinery and postsynaptic NMDA receptors If no additional input, they remain silent because they lack sufficient AMPA receptors Activity recruits AMPA to activate synaptic activity

Answer 296

Declarative (facts/events) and non declarative (unconsciously) Long and short term

Answer 297

Excitatory - glutamate - leads to depolarisation | Inhibitory - GABA - hyperpolarisation

Answer 298

- Regulated of voltage gated Ca2+ channel - activation released neurotransmitters - Position of Ca2+ channels - closer it is to the vesicle containing neurotransmitters, the less depolarisation required for its release

Answer 299

They interact with each other and drive the synaptic vesicle to its release - releasing neurotransmitters

Answer 300

Calcium sensor - without it the channel wouldn't be calcium dependant - Some require different concentration of calcium to activate it - change its sensitivity

Answer 301

Readily releasable poll - close to the membrane Proximal pool - substitute readily Reserve pool - resting pool

Answer 302

The speed of release for readily releasable is quick but speed of conversion of proximal pool to readily releasable is slower - there will be a tie when no vesicles are ready to be released - lose sensitivity

Answer 303

NMDA receptor AMPAR - Non NMDA receptor mGlut receptor

Answer 304

Bound to G protein - activation activates adenylate cyclase - phospholipase C - involved in increasing Ca2+ in cytoplasm

Answer 305

Na+ channel | - Bind glutamate - Na+ influx - depolarisation

Answer 306

Selective for Ca2+ - Has a Mg2+ bound to the pore region - needs to depolarise membrane to move it - just binding of glutamate is not sufficient

Answer 307

Large neurones Circuit complexity Temperature- dependance Genetically mapped

Answer 308

Habituation - Responds less after repeat stimuli | Sensitisation - Nervous system responds to stimulus more and more

Answer 309

Habituation of eye blink reflex | Habituation of relative non harmful stimulus - e.g. living on a busy road

Answer 310

Reflex in aplysia - snails 2 organs - Responsible for withdrawal reflex requires 2 neurones - sensory neurone activated with touching the siphon - glutamate - motor neurone contraction to remove

Answer 311

Test which neurone becomes desensitised by recording from each neurone - From sensory neurone - same response overtime - terminals are not desensitised - Record from motor neurone - same - Record from both and you can see response getting smaller with repeated stimulus - Concluded that it is the synapse that desensitises

Answer 312

Synapse desensitises | - Less than 50% of neurotransmitters are released

Answer 313

Addition of painful stimulus just after - Sensory neurone activated by touching siphon - L29 neurone stimulated by a shock - L29 activation leads to the release of serotonin - activates receptors and G proteins - adenylate cyclase converts ATP and CAMP - activates protein kinase A which inactivated K+ channels in synapse - Prolongs depolarisation - more vesicles released during one depolarisation - Bigger contraction of muscle - Sensitisation

Answer 314

Weak siphon touch paired with strong shock - Paired stimulus - withdrawal reflex is very large - lasts long - Timing is critical

Answer 315

Ca2+ influx due to depolarisation | Serotonin release

Answer 316

In addition to synaptic plasticity, other mechanisms can directly involve the synapse

Answer 317

- Single trail associative learning - Present attractive feeding stimulus stimulus (sucrose) - snails will eat it because its sweet - Also a neutral stimulus present (amyl acetate) - Pair them - Then snail shows feeding behaviour to amyl acetate alone - association

Answer 318

Serotonergic cerebral giant cells contact many cell types and permit feeding but not involved in feeding behaviour - if it fires feeding is possible if It doesn't its not

Answer 319

24 hours after the trial the resting potential of the serotonegic cerebral giant cells had raised by 10mv - Only change seen - The depolarisation lasted for weeks - Depolarisation occurs after the behavioural change

Answer 320

Depolarisation needed for long term memory but not short term Long term memory at least partially encoded at a site distant to the neurones

Answer 321

Necessary: Hyperpolarise neurones and train the animals Sufficient: Depolarise neurones on untrained animals Results showed it was sufficient

Answer 322

Dentate gyrus CA1 CA3

Answer 323

CA1 and CA3 synapse

Answer 324

High frequency stimulation - causes summation of EPSP's | Causes long term potentiation

Answer 325

The entorhinal cortex

Answer 326

Two pathways converging on the same target can both be strengthened if they fire together as long as membrane is depolarised

Answer 327

No stimulus just needs to depolarise the membrane

Answer 328

Evidence suggests post

Answer 329

AMPA - depolarise post synaptic neurone | NMDA - Selective for Ca2+

Answer 330

Mg2+ ion binds to the pore of the receptor and blocks the channel from glutamate In order to remove glutamate, the membrane of the post synaptic neurone must be depolarised This is a key mechanism for long term potentiation

Answer 331

Tetanic stimulation ---> glutamate release ---> AMPA receptor activation ---> Depolarisation ---> Mg2+ removal ---> NMDA activation

Answer 332

Early - Does not require protein synthesis | Late - requires protein synthesis

Answer 333

NMDAR mediated - Ca2+ released and activated calmodulin kinase II - CaM - NMDA receptor is opened and autophosphorylated so that it remains open even after Ca2+ is gone - Prolongs the activity of calmodulin kinase II

Answer 334

Apply glutamate for short term and wash it out Trigger long term potentiation Apply glutamate again Saw that AMPA currents increases

Answer 335

- They allow the animal to develop properly first and then add them - Not 100% specific - usually inactivate something else as well

Answer 336

Specific | Don't develop properly as effected many processes

Answer 337

- Change the open probability of the AMPA receptors - open more - May involve amplification - increased number of AMPA receptors on the post synaptic site

Answer 338

1 hour after stimulation

Answer 339

Important in the regulation of gene expression - Activates protein CREB-2 (calcium response element) - blocks expression of gene - CREB1- Replaces CREB 2 and activates gene expression and is phosphorylated by protein kinase A

Answer 340

Glutamate activates AMPA Depolarises post synaptic membrane Removes Mg2+ block Ca2+ moves in through NDMA Activates calcium calmodulin Activates adenylate cyclase and calcium calmodulin kinase Activates protein kinase A - gene expression ---> proteins go to synapse Calmodulin kinase 2 phosphorylates AMPA receptors --> increased numbers due to exocytosis

Answer 341

Behavioural test - Animal model had to learn something - Then inhibit LTP by inhibiting NDMA receptor - Check if animals memorise less - Inject inhibitor in hippocampus - Could also over express something required in LTP and see if animals learn better

Answer 342

There are different types of synapses - some don't use NMDA receptors, some don't use CamK11 - LTP varies in non hippocampal areas

Answer 343

Hidden platform in water for mice - First time they look for it, second time they know where it is Use knockout mice of CaMKII or NMDA receptors - cant find it as quick

Answer 344

No | It is only necessary for some memory formation

Answer 345

Active evoked long-lasting reduction in synaptic efficacy

Answer 346

``` Depotentiation - Removal of previous potentiation - Reversal of long term potentiation Long term depression de novo - No previous potentiation ```

Answer 347

- Often requires NMDA receptors but not always - Often evoked by low frequency stimulation but not always - Often requires Ca2+ influx and activation of serine, threonine phosphotases - Often involves glutamate but also diffusible transmitters eg. 5-HT

Answer 348

The cerebellum receives in pt from two fibres - Mossy fibres - synapse with granula cells - climbing fibres which synapse with one purkinje cell

Answer 349

Because there are many synapses to one purkinje cell | - Main output of cerebellum is purkinje cell

Answer 350

If stimulate just parallel - ESPS | If stimulate both - the amplitude of ESPS in purkinje cells is much smaller - Long term depression

Answer 351

Climbing fibre input indicates a motor error and therefore weakens the parallel fibres so synapse between parallel fibre and purkinje cell is weakened

Answer 352

metabotropic glutamate receptors and voltage gated Ca2+ channels are involved

Answer 353

Climbing fibres activated - release glutamate depolarisation of purkinje cells - activation of post synaptic Ca2+ cells - Ca2+ influx Parallel fibres activated - GPCR cascade activated phospholipase C - DAG - activates protein kinase C The two pathways interact with each other - increases protein kinase C more Protein kinase C then phosphorylates AMPA receptor on a different side to the LTP Leads to endocytosis of AMPA and reduction in AMPA receptor current

Answer 354

If the synapse of the cell is active but the rest of the cell is not depolarised then it becomes weakened

Answer 355

The degree of NMDA receptor activation If activated a small amount then LTD and if more than LTP - because LTD has mainly phosphatsaes which are triggered by NMDA receptors response to a small increase in Ca2+ - LTP has mainly kinases - large increases of Ca2+ lead to more kinases to increase AMPA efficacy

Answer 356

On group of marmosets are in enriched environments and another not - Looked at morphology of neurones - Counted numbers and density of post synaptic boutons - Increased number of dendritic spines - Not only change strength of synapses but change shape and number of them too - So memory is not just LTD and LTP but it is involved

Answer 357

Retrograde - previous memories not intact | Anterograde - inability to form new memories

Answer 358

``` Transmitters eg. glutamate or GABA Receptors ECM - 'glues' synapse other neurones Glial cells - control the extracellular environment eg.ion concentrations ```

Answer 359

So that Na+ channels can open when membrane potential increases and to keep them closed when needed

Answer 360

Pumps/transporters - to regulate ionic gradients Na+, Ca2+ channels - depolarisation K+ channels - to terminate action potential

Answer 361

By changing what channels and transporters are present in the membrane of the neurone

Answer 362

By changing the channels present in the membrane Also by glial cells - Astrocytes increase causing extracellular [K+]to decrease from 35mM to 3mM

Answer 363

No action potentials are seen early as well as neurones. develop at different stages

Answer 364

The measure of the ability of the cells for current to flow across the membrane - can be changed due to channels being inserted into the membrane

Answer 365

How quickly the neurone can respond to a cell

Answer 366

Resistance and the capacity (ability to store charge) of the neurone

Answer 367

Because neurones get bigger

Answer 368

They both decrease

Answer 369

Long Ca2+ dependant then short Na+ dependant action potentials Short Na+ dependant

Answer 370

They are a transit population of mechanosensory neurones found in the spinal cord

Answer 371

Looks like a cardiac action potential because it is Ca2+ driven - Calcium is let in and the channels don't shut quickly - Not many K+ channels present to terminate so action potential appears elongated

Answer 372

Delay rectifier K+ channels are inserted into the membrane - open after a delay after activation So after Ca2+ open, K+ channels ope after a delay so action potential is still a bit elongated

Answer 373

Normal action potential as Na+ channels have been inserted More sensitive Fast firing - Occurs due to Na+ channels will snap shut quickly after it depolarises and also allows K+ channels to open to allow it to repolarise

Answer 374

Channel that allows current through one way A delayed rectifier is a channel that opens some time after its voltage threshold is reached Outward delayed K+ rectifiers allow positive charge out of neurones after an action potential Appearance of such channels shortens the action potential

Answer 375

Mouse cortex - Different spiking activity as neurones develop - fast spiking cells increase Kv3.1 expression the mature allowing to depolarise quicker Purkinje cells bursting pattern - Regulated by KCa channels increased expression - Opens in response to influx of Ca2+ - Blocking these K channels stops the mature bursting pattern

Answer 376

Give the action potentials in early development

Answer 377

found in axon terminals ad control neurotransmitter release

Answer 378

Controls transcription

Answer 379

Process growth | Involved in differentiation

Answer 380

Neuronal development - Populations - Subunits - Localisation - Efficacy

Answer 381

There is high intracellular [Cl-] in immature neurones - Cl- channels on membrane have changed meaning that it pumps Cl- out instead of in - GABA still activates these receptors meaning it has an excitatory role

Answer 382

Traumatic injuries in PNS, spinal cord and brain Stroke Loss of neurone in disease eg. Alzheimers

Answer 383

Can regenerate whole limb with or without the presence of a nerve

Answer 384

Tail regeneration is dependant on BMP signalling Has a critical window of response - At 47 hours of development - ail will not regrow

Answer 385

Needs the radial nerve to be intact for limb to regrow

Answer 386

``` Neuropraxia - Mildest - No physical peak but block of conduction Axonotmesis - Sectioning of axon but preservation of nerve itself Neurotmesis - Severe - Whole nerve is sectioned ```

Answer 387

If it is close to the cell soma - likely for cell death Away from cell soma - cells might survive but will undergo changes such as reorganisation and re expression of the immature features eg. tubulins

Answer 388

Discovered in 1840 and is the first state of regeneration in mature nervous system - Part of the damaged axon furthest away from the soma (distal end) degenerated by macrophages trying to remove dying Schwann cells - The part closest to the soma remains the same - Occurs quite quickly so a new one can be made

Answer 389

Muscle atrophy - AChR start to change to a immature form - Muscle specific kinases increase - If external electrical input is added it my help to prevent atrophy

Answer 390

Wallarian regeneration Mitosis of Schwann cells - To cover area to help axon grow - Also form bands of bunger to guide the new axon Sprouting may also occur - Another nerve tries to innervated the muscle to prevent loss of function

Answer 391

``` Compression - Basal lamina damaged and ECM unaffected Cut - Disrupts both basal lamina and ECM - May not regrow accurately ```

Answer 392

Sprouting may be attempted but the fibres cannot find where they need to be so - failed regeneration Formation of cysts and glial scars

Answer 393

Damaged axons from CNS where put in the environment of the PNS They were able to regenerate unlike in the CNS Suggesting environmental factor and not intrinsic

Answer 394

CNS neurones were trying to avoid oligodendrocytes Removing myelin/oligodendrocytes improved regeneration If you auto-immunise a micr to myelin proteins - enhances regeneration

Answer 395

NOGO -a (protein)

Answer 396

NOGO - a - large and donut in oligodendrocytes NOGO b - Many cells NOGO - c - muscle

Answer 397

NOGO a is not found in the fish and salamanders or in human PNS which can regenerate

Answer 398

Works on P75 receptors interfering with the roles of neurotrophins which support the development of new fibres

Answer 399

Knockout mice showed variable results No correlation between NOGO receptor level and regenerative capacity Transplanted hippocampal neurones grow axons Much myelin is removed by macrophages after damage

Answer 400

When astrocytes are damaged they change in other to contain the inflammation This causes a scar which fibres can not grow through

Answer 401

Gap in nerve that is too big Scaffold tube inserted which connected the nerve and allows fibres to grow inside it - Can be synthetic or biological - If synthetic it wold have to be filled with ECM

Answer 402

Parkinsons and Huntingtons | - Little success

Answer 403

Transplanted foetal cells Transplanted human embryonic stem cells Transplant umbilical cells Transplant autologous NS cells

Answer 404

Canaries - In their high vocal centre, new neurones are formed as the canary learns to sing - Suggests that neurogenesis can occur in mature animals Mammals - In dentate gyrus (in hippocampus) and olfactory bulb, neurogenesis can occur naturally

Answer 405

if there are stem cells capable of neurogenesis then they could be used for spontaneous regeneration under the right conditions

Answer 406

Supporting cells | - Support and encourage regeneration

Answer 407

Without Shh, mouse wouldn't live long enough to reach the stage where commissural axons cross the midline Cre recombinase can be used to knockout shh just from the tissue being studied so that the rest of the development is normal

Answer 408

BMPs are released from roof plate and BMP is a repellant | Shh is released from floor plate and Shh is an attractant