Building Nervous System Flashcards
what are the two parts of the nervous system?
CNS and PNS
how many ways can the PNS be spit up? and what are they?
3
how they connect to CNS? cranial or spinal nerves
direction of propagation? afferent or efferent
motor neurone’s target effector? somatic or autonomic (sympathetic or parasympathetic)
why are studies of lower species e.g. rates still useful in the understanding of human brains?
this is because all vertebrates share the same basic architecture of the nervous system. there are just systematic changes in brain structures.
describe from fish to humans, the different change that happen at each stage
fish - some tubes to carry nerve from distal parts of the body to a rostral point
reptilian brain - nerves sorted into specialised modules e.g. light sensitivity = vision, chemrsensitivity = smell etc. bulge on rostral area of spinal cord, connected to the cerebellum
mammalian brain - hypothalamus allowing reaction to more stimuli. thalamus developed allowing hearing, smell and vision to work together. amygdala and hippocampus allow for crude memory and limbic system generates emotion but they aren’t able to be experienced s it is unconscious
human brain - developed 1.5 million years ago. exposure enlargement of specific areas associated with thinking, planning, organisation and communicating. a larger cortex push cerebellum to current position. skull bones used outwards forming high flat forehead and domed head
what are the planes of sections of a human brain?
sagittal
coronal
horizontal
how many lobes of the brain are there and what is the main attribute of each one?
4 frontal ; personality parietal ; abstract mathematical functions occipital ; vision temple ; hippocampus
what is the function of white and grey matter?
grey matter - which is grey due to its lack of myelin, have cell bodies which are the ‘computer zone’
white matter - a connection between cell bodies. all various computing units can talk to each other, share information, divide work up and checks that conclusions made are reasonable. sends information to specialised computing areas
what are gyri and sulci of the brain?
gyri - ridges
sulci - creases
what is the cerebellum involved in and what could result from deficiencies in it?
cerebellum is involved in: balance,movement, reading and writing
dyslexia can be due to problems with the cerebellum
describe one specialised area of the brain
Brodmann's area - it is a systematic map of the brain based on cell types. for example with speed, there are: Broca's area (44) - specialised motor area involved in the mechanical production of speech. controls the lips and the tongue Weirnickes area (22) - involved in grammatical rules for language
what are ‘hard-wired’ areas of the brain and give examples of these
hard wired areas are areas where given appropriate conditions, the cells should develop into their genetically preordained form and function.
the motor cortex is for movement and the visual cortex is for vision
why has evolution made it essential that humans have specific attributes?
vision
ability to move precisely
faculty of speech
these are all so that humans have an evolutionary advantage over rivals so that these attributes and our genes can be selected for and the species live longer
what is the explanation for attributes that have no obvious evolutionary advantages? and give an example of one
playmusic could be an evolutionary advantage as the ability to play music and the intelligence and sensitivity required to play an instrument may be attractive to the opposite sex which means that those genes armoire likely to be passed on
how do musicians differ from the rest of the population ?
there is a hook that is in the motor cortex which is an area that controls the hand. in the dominant hand, from a frontal view, this is the shape of an inverted omega in 90% of the population and the shape of a lowercase omega in 10% of the population which is in concert pianists, suzuki players etc
what is the reason for an increased size of the hook in musicians?
this is due to the neurones sprouting new connections because they must allow for the signals to get to the correct muscles at the correct time in the correct order.
define plasticity
the ability of neurones to create new connections and also destroy old connections in response to new physical demands
what makes the brain such a powerful processor?
each neurone can make 1000-10000synapes
the human brain has 10^11 neurones
thus, 10^14 connections are in the human brain
describe the overall evolution of the brain
in higher mammalian brains, the development of increasingly complex senses triggered the development of a thin layer of cells on the brain’s surface called the cortex. from which, consciousness emerges. the cortex allows for many neural connections with only a small increase in size
what are the three main features of simple cell organisms? give an example of it in action
receptiveness, responsiveness and spontaneity
eg euglena : spontaneous swimming activity, responds to light and the photons transducer by pigment are localised to the eyespot
what comes with multicellularity?
specialisation and the appearance of a nervous system
give an example of a multicellular organism and describe it
sponges
water flows in through the body wall
water flows out of them through the osculum (large hole at the top)
the flow is controlled by the beating of flagellated cells
and is regulated by the myocytes which are specialised cells tat respond to stretch - can do this becuase of their contractility
describe primordial nervous systems
there is an appearance of neurones and the first one is probably a sensorimotor cell. they span from the exterior to the effector cells
what is a hydra?
it is a multicellular organism which feed themselves using tentacles which are also used to locomote through the environment by tumbling
there is a derivation of different types of neurones from ectoderm for example motor neurones and interneurones
motor neurone - receive input from true sensory neurones and output - to effector cells and other motor neruones
interneurones lie between sensory and motor neurones and excitation or inhibition allows for more complex responses
what are the two types of worms?
segmented and non segmented
what do flatworms clustering of neurones show?
- GBCFC
- ganglionisation
- cephalisation
- bilateral symmetry
- fasiculation
- commissures
give an example of a segmented worm
annelids - fusion of longitudinal nerve cords
how many neurones anglia do c.elegans have?
302 neurones, 56 glia
what kind of nerve cords do c.elegans have?
dorsal, ventral and lateral nerve cords
where do most neurones derive from?
from AB cells that have a shared lineage with the hypodermis (skin)
describe the formation of a neurone in insects
the neurogenic region is next to the ectoderm (future skin)
there is then migration of the neurogenic region as gastrulation proceeds
individual neuroblasts delaminate and migrate inward then coalesce.
how are glia and neurones formed in drosophila ?
neuroblasts form ganglion mother cells
ganglion mother cells form neurones and glia
in drosophila, what does delamination form ?
neuroblasts
where is the nervous system on vertebrates?
it is dorsal,
what is the hypothalamus also known as? and what is it close to?
the autonomous integrating centre
it is close to the pharynx (the mouth)
what is the difference between insects and amphibians in the way that the neurogenic region develops?
the neural cells do not laminate
the neural cells stay as one layer called the neuroepithelium which can often be called the neural plate
where does the nervous system of all vertebrates arise from?
the neural plate
how do cells become neural precursors differ in insects and vertebrates?
in insects, single cells become neural precursors
in vertebrates, whole groups of cells/sheets of cells become neural precursors
where do neural precursors first form in worms, insects and vertebrates?
at the surface. they develop next to the skin on one side and next to the mesoderm on the other side
define cell differentiation
the process by which cells become different from each other and acquire specialised properties.
what is cell differentiation governed by?
changes in the gene expression, which dictate the repertoire of protein synthesised.
what can gene expression of a cell be governed by?
intrinsic (transcription factors) and extrinsic (morphogens) factors
how does the neurogenic region arise?
through inhibition of BMP signalling
describe the process of BMP inhibition and explain what the homologue for it is in insects
BMP signalling is inhibited by an antagonist - chords
BMP and chordin are proteins that have been high conserved through evolution
in insects, the BMP homologue is app and the chords homologue is short-gastrulation (sog)
what does the dpp/sog network do ?
it broadly dictates dorsal and ventral sides of the body in insects/worms. where dpp is inhibited by sog, the neurogenic region arises.
at what point does the neural plate form in insects?
the neural plate broadly forms where dpp inhibits sog
at what point does the neural plate form in vertebrates?
the neural plate broadly forms where chordin inhibits BMP (same as in insects but reverse)
what is the molecular pathway for the development of a neural plate cell (ectoderm)?
the ectoderm can form either an epidermal cell or a neuronal cell
define neurulation
when the neural plate rolls up to form the neural tube, so the vertebrate development progresses
what is SMAD 1?
part of a secondary signalling cascade
how does the neural plate cell become epidermalised?
BMP must bind to SMAD to phosphorylate it. this would then activate a pathway enabling the cell to become an epidermal keratinocyte
what happens to the fate of a neural plate cell in the absence of BMP?
BMP can’t activate SMAD1 so SMAD 1 can’t enter the nucleus. this means that a different set of transcription factors are unregulated which starts their transcription. this can cause the differentiation of a cell to a neurone.
what are the epidermalising transcription factors and what condition is needed for this to happen?
MSX1, GATA and Vent with BMP present cause an epidermis to develop
what are the neuralising transcription factors and what condition is needed for this?
XLpok2, SoxD with the absence of BMP
how has the understanding about neuralation formed?
though studies on xenopus. following fertilisation, the egg undergoes cleavages and gives rise to 3 hollow balls of cells. 3 germ layers will form called the ectoderm, mesoderm and endoderm.
how do we know that the cells in the germ layers are different form each other ?
analysation of the of the transcriptome and proteome in each part, can find 3 big categories of genes then find their proteins and do immunohistochemistry on them to see that the cells are transcribing different proteins.
what is produced when transcription factors e.g. Gse are in the ‘organiser’ ?
in the mesoderm layer, there are specialised mesodermal cells that are induced called the organiser. it expresses special transcription factors and secreted ligands including chordin
under the influence of transcription factors such as Gse, the organiser expresses unique secreted products that are all antagonists of the BMP signal
what do cells in the organiser turn into?
anterior ectoderm, prechordal mesoderm and anterior neural plate. 1 and 2 become axial mesoderm.
define neural induction
the process through which the neural plate forms when BMP antagonists prevent the BMP ligand from stimulating its receptor
what is noticed as the neural plate forms the neural tube?
development of the axial mesoderm
cells in the organiser differentiate into anterior endoderm adaxial mesoderm. these involute, intercalate and undergo convergent extension
after it is induced, dorsal mesoderm involutes and undergoes convergent extension. as it does so, it self differentiates into notochord. convergent extension alters the shape of the developing embryo
as these processes occur, the neural plate grows and elongates making the A-P axis and rolls into the neural tube
what is noticeable about developing nervous systems?
i developing nervous systems, the anterior end/prechordal mesoderm are in close contact with the pharynx and the ventral forebrain
describe the experimental proof for neural induction
in the 1920s, the organiser graft experiment was done by Spemann and Mangold. they grafted the organiser from a donor to a host newt and found that a twinned embryo developed with a complete secondary neural axis.
the secondary neural tube was host derived i.e. showing that the neural tissue is induced from the ectoderm in response to signals from the organiser tissue.
the exile mesoderm and anterior endoderm were donor derived showing that they had self-differentiated from the organiser.
is there any support foremother studies for spemann’s organiser?
Henson’s node grafted from quail embryo to chick host and also found that a new axis was induceed in the host
where does the ability to be neural inducing or the mesodermal dorsalisation come from?
from the ability to synthesise and secrete various BMP antagonists e.g. chordin, noggin, follistatin etc.
how were BMP antagonists in the organiser discovered?
by BMP antagonists having all of it’s mRNA extracted from organiser cells, reverse transcribing them to cDNA then testing each to look for a gene/protein that would mimic the organiser’s ability to induce a secondary neural plate
what experiments can be done to prove a molecule is a neural inducer?
-molecule must be expressed the organiser
-molecule must be secreted and act on adjacent cells
-over-expression of the molecule at an ectopic site should lead to induction of the secondary axis
-inhibition of activity should prevent axis formation
these types of experiment show that BMP signalling is NECESSARY for neural induction
what are the 2 types of experiments that show that BMP antagonists give neural tissue ?
- express BMP antagonist ectopically
2. dominant negative experiments with BMP receptors
what are the 2 types of experiments that show that BMP antagonists give neural tissue ?
- express BMP antagonist ectopically
2. dominant negative experiments with BMP receptors
where are the majority of the neurones in the brain?
in the cerebellum and the cortex
what are the steps in embryogenesis?
CNS PNS Midbrain Hindbrain Spinal cord
where does all of the nervous site arise from?
the neural plate
at what point in development do the main parts of the nervous system become established?
easy in embryogenesis (3-5 weeks in humans)
how do we know that all the main different parts of the nervous system begin to be established very early in embryogenesis?
as the organiser/node begins to differentiate into the axial mesoderm, it involutes and undergoes convergent extension and extends under the newly induced neural plate.
if development is stopped at this point, and look with molecular markers, can see that the neural plate is expressing markers that are aper confined to the forebrain (early neural plate=anterior in character)
this is because BMP antagonists induce neural tissue that has anterior identity. BMP antagonists are made in the early node and in the prechordal mesoderm have different characteristics, providing signals that promote proliferation and growth of neural cells and their ‘posteriorisation’
the posterior nervous system then develops as the node regresses, posteriorly. axial mesoderm laid down in its wave. it induces proliferation and growth of the neural plate/neural tube.
this idea is known as the activation transformation model
describe the main concept of the activation transformation model
-neural inducing molecule induce anterior tissue
these molecules initially come from the early node/organiser cells but are maintained in the prechordal tissue
-other signals from later node/organiser promote growth and posteriorisation
ANTERIOR AND POSTERIOR SIGNLAS ACT ANTAGONISTICALLY
what is the model basis for the activation transformation model?
- BMP inhibitors from the organiser tissue block the formation of epidermis, ventrolateral mesoderm and ventrolateral endoderm
- Wnt inhibitors in the anterior of the organiser allow the induction of head structures
- a gradient of caudal factors specify the regional expression of Hox genes
where are BMP antagonists and Wnt antagonists maintained?
BMP antagonists and Wnt antagonists are maintained anteriorly
what are the caudal factors, where are they expressed and what do they do?
FGF, Wnts and RA are expressed posteriorly and promote growth and posteriorisation
how is a core regional pattern in development established?
by placing 2 antagonistic molecules at each end of a forming structure.
how is the nervous system along the AP axis?
it is segmented along the AP axis
what are the two main models of transforming gradients?
the Lewis Wolpert ‘positional information’ / french flag model
the Alan Turing ‘reaction-diffusion’ model
in drosophila, what is segmental identity controlled by?
homeotic (hox) genes - they provide positional information for the drosophila
give 5 facts about the homeotic genes
they are transcription factors
they have a shared homeodomain box with DNA - so is a useful marker
they specify AP segment identity in dropphila
they have been evolutionary conserved
many hox genes develop through adulthood
how can you experimentally find the function of hox genes?
must KO many hox genes to find the function - because especially in humans and mice, there are many of the same gene
what was found when the KO of hox a1 and hox b1 was done?
that they are required to specify rhombomeres 4 (partially) and 5 and the nerves that are normally made from this region
what forms at the edge of the neural plate and ectoderm? what is it for?
a specialised border of cells forms at the edge of the neural plate and the ectoderm. it is crucial for neural crest formation and roof plate formation and dorsal neural tube patterning/differentiation
what are the different steps for the neural crest formation?
there are 5 steps
- an early border is established at the interface of the induced neural plate and surface ectoderm. this begins to express specific transcription factors (msx1) thought to be induced at ‘intermediate’ levels of BMP signalling
- other signals (wnts, FGFs) act together with msx1 to turn on other transcription factors (Pax 3, Zic 1, Pax 7). the combo of these tfs characterise the neural pate border cell
- Wnt signals act together with NpB tfs to up regulate further tfs (c-myc, ld, snail etc) that characters neural crest cels. many of these tfs, we know to give stem-like behaviours - proliferation and multi potency
- in response to c-myc and sox-9, genes that control proliferation and mulitpotency and survival are transcriptionally activated
- at the same time, neural crest cell tfs upregulate a further set of genes that promote epithelial-mesenchymal cell transit (EMT). neural crest cells delaminate from the border region and begin to migrate.
what are neural crest cells also known as?
the 4th germ layer
what do neural crest cells give rise to?
a number of different types of cells of the body including scwann and neurological cells and also the sympathetic and parasympathetic system in the PNS
what are the different cell types that the neural crest cells will develop dependent on?
the position of origin of neural crest cells
timing of generation of neural crest cells (determined by Hox genes)
migratory pathway and the signals they encounter en-route or at the target
what are the three main pathways of neural crest migration in a chick embryo
superficial pathway - (beneath ectoderm) form pigment cells on the skin
intermediate pathway - (via somites) form sensory glia
medial pathway - form sympathetic ganglia and cells of adrenal medulla
do all neural plate border cells for neural crest cells?
no, a few are retained at the border and form roof plate ells. these are important in the in a step if neuralation and dorsal neural the patterning
what happens to the floor and roof plate when a neural tube the is developing into a spinal cord?
a floor plate of non-neuronal cells develops along the ventral midline ad a roof plate f no neuronal cell along the dorsal line
where neuronal cells develop nearest to the floor plate?
neuronal cells whose phenotype is not known
where do future motor neurones commissars neurones differentiate ?
immediately above the floor plate, in the dorsal region, near the roof plate
what do roof plate cells up regulate?
BMPs and Wnts that diffuse into the dorsal neural tube. they induce the expression of a set of tfs (pax 6,7,2 and Lim1) that cause neural tube progenitors to acquire ‘dorsal identities’
what was thought about BMPs that come from the roof plate?
that they were morphogens that induce different types of dorsal cells.
what is actually true about BMPs and Wnts?
recently has been found that they express many different BMPs, each of which induces particular dorsal cell types.
they induce different sets of progenitor cells that will ultimately differentiate to distinct neuronal subsets in the dorsal spinal cord
what is happening to the axial mesoderm at the same time that the neural plate/early neural tube is forming?
the axial mesoderm forms also and comes to lie just below the ventral midline of the neural tube
how do neurones develop around the midline?
neurones develop around the midline, throughout the entire torso-ventral axis (D-V)
where are floor plate cells and the notochord located and what do they secrete?
they are located at the ventral midline and secrete morphogens
what is the test of if notochord and the floor plate cells diffuse
test by grafting a donor notochord or floor plate to an ectopic position is a host embryo. ask if ectopic floor plate / and ectopic neurones are induced. ectopic floor plate and ventral neurones such as motor errors, induced after a graft of the notochord/floor plate
what is the secreted factor made by the notochord and floor plate?
hedgehog which was the name given as the fruit lies look curled up and spiky.
what is the hedgehog gene?
a factor that has been conserved in evolution, that has a homologue in drosophila.
in the 1980s, what did researchers realise about the conservation of hedgehog?
that hedgehog and shh were conserved between invertebrates and vertebrates
where is Shh mRNA expressed?
in the notochord and then the floor plate
is Shh protein or mRNA detected more widely?
Shh protein. this is because it appears in a gradient as it diffuses through the ventral neural tube from ventral to dorsal
what was the 1st evidence that Shh has a diffusion gradient and can therefore be detected more easily then Shh mRNA?
when an antibody was made against the Shh protein, it was shown to diffuse away from the notochord and floor plate, forming a concentration gradient the ventral part of the neural tube. Shh comes from the notochord and the floor plate and Shh signalling induces expression of transcription factors in progenitors cells. these transcription factors confer ‘ventral’ neural tube identities, so the progenitors will ultimately give rise to cells that differentiate into ventral neurons.
how can an ectopic floor plate and ventral neurones be induced?
An ectopic floor plate and ventral neurons are induced after implantation of a shh soaked bead. This is because the bead soaked in purified Shh protein can mimic the effect of notochord/floor plate
the transcription factor ‘code’ dictates later differentiation
as cells (nerves) differentiate, they move laterally
what is the name of the transcription factor that dictates later differentiation?
code
what direction do cells move as they differentiate?
they move laterally
what is the action of Shh at an early stage ?
it acts to confer a DV pattern of transcription factors on progenitor cells
what is the job of tfs upstream?
the transcription factors are the upstream ‘master’ regulators of particular neuronal fate/identity
what patterns the DV axis?
OPPOSING gradients of BMPs and Shh PATTERN THE DV AXIS
in what conditions do cells change there fate?
in accordance with their position in the Cartesian grid. this means that different types of neurones differentiate at the same D-V position along different parts of the AP axis
give 4 examples of what Shh induces in different parts of the body
-forebrain, it induces hypothalamic neurones
-midbrain, it induces dopaminergic neurones
in the hindbrain, it induces serotonergic neurones
-spinal cord and everywhere else, it induces motor neurones
what does the neural tube initially look like and what changes during dark neural tube development?
initially, the neural tube is a single layered neuroepithelium. during early stages neural tube development, some cells continue to ‘span’ the width of the neural tube. their nuclei migrate back and forth at different stages the mitotic cycle.
what are cell that derive from the stem-like neuroepithelium called?
radial glia. they are thought to be the later neural stem cells
where does the division of radial glia occur? and what is the product of this?
in the lumen. it can divide to form 2 radial glial daughters or a radial glia and a proliferating daughter progenitor - depending on the plane of division.
where do the proliferating daughter progenitors and differentiated cells move into after division?
proliferating progenitors move to the adjacent ,mantle zone (largely picked through various tfs e.g. Nkxx, Pax etc)
differentiated cells move away into the marginal zone
what is the difference the amount of neurones that can be produced in proneural vs neurogenic mutants?
mutants lacking proneual activity cannot form neurones but neurogenic mutants form too many neuroblasts
what is the role of notch and what occurs in its mutants?
it controls the number of cells that from neurones. as it is required to prevent a cell from becoming a neuron. in notch mutants, too many neurones are made.
what happens to a cell suppressing notch?
it will become a neuron
how does notch work?
locally as it is a juxtacrine signal. it woks on adjacent cells
what happens in a fly where there are cutters of cells that have activated pro neural genes
these cells are now competent to become neurones - although only a few actually do
what does notch regulate?
lateral inhibition
what does notch regulation include?
involves the transmission of an inhibitory signal between a pair/cluster of cells to prevent cells that receive the signal from adopting a particular cell fate
what is notch and deltas link?
notch is the receptor for the delta signal
describe the steps of lateral inhibition
initially, both cells are equally capable of making and receiving the inhibitory signal.
subsequently, a change or bias is introduced - perhaps randomly- so that 1 cell begins to make more inhibitory signal
consequently, the second cell receives more inhibitory signal and becomes inhibited.
what is needed to stabilise the change of lateral inhibition?
the inhibited cell must be prevented from continuing to send the inhibitory signal
what is the importance of balance in notch signalling?
in a pro neural region, notch signalling is balances. a slight imbalance develops and it is then quickly amplified, leading to the development of a neuronal precursor.
what is special about the progenitors that don’t differentiate?
they have a certain shape
they exist as radial glia
they provide a pool of undifferentiated cells that are used to build up the nervous system over time in embryogenesis
what does the daughter cell of radial glial cells do when it is migrating away?
they use the scaffold provided by its sister to migrate away from the ventricular zone
what is the arrangement of the motor system?
its arranged hierarchically
what are the different layers of the motor system hierarchy?
- highest level :primary motor cortex
- middle level: brainstem
- lowest level: spinal cord
what is the projection of the primary motor cortex? what does it regulate?
projects directly into the spinal cord via the corticospinal tract
regulates the motor tracts that originate in the brainstem
what is the pathway of the brainstem and what does it control?
lateral descending system controls distal limbs
what does the spinal cord modulate and why can it do this?
modulates reflexes automatisms such as walking as well as many other actions. can do this because it contains neuronal circuits.
what neurones have the simplest reflex?
the monosynaptic sensory neurone and motor neurones
what is the majority of reflexes in the body ?
polysynaptic with interneurones
what is the pathway of the brainstem and spinal cord? what do they control?
brainstem = lateral pathway that controls the hands and arms
spinal cord = direct pathway to the muscles and reflexes
what happens if you artificially stimulate the spinal cord,brain stem and the spinal cord?
you would only get twitches [from the speech motor areas (e.g. brooks area) and simple vowel sounds]
what is the motor acton of the basal ganglia and the cerebellum?
they receive information from many different areas if the cortex and project to the motor cortex via the thalamus
they are aware of the situation a person is and they monitor commands going down to the muscles to make sure that they are appropriate
where does the basal ganglia feedback to?
the basal ganglia only feeds back to the motor cortex - subcortical loop
where does the cerebellum feedback to ?
the cerebellum mainly feeds back to the motor cortex but can send its signals down to the brainstem, spinal cord and onto the muscles - direct output onto the spinal cord and is an internal subcortical loop
what happens if you stimulate different areas of the frontal lobes?
it produces movements on the opposite sides of the body
what was done in the mid 20th century to identify motor effects in the frontal lobes?
electrical stimulation was done to identify specific motor effects pf discrete sites in the frontal lobes in different species- especially in humans and primates
(wilder penfreid 1891-1976)
what are association areas in the brain for?
they are to support the primary areas of the brain
what was found about brodmanns area in terms about stimulation eliciting movement?
brodmann’s area 4 was found to be an area in which the lowest intestate stimulation elicited movement - in the primary motor cortex
where is the brodmann’s area located ?
in the primary motor cortex which is located just before the central sulcus (fissure of Rolando)
what is the name of the motor cortex first neurones?
the upper motor neurones (UMN) which carry the motor commands own through the brain, brainstem and the spinal cord
where does the spinal cord originate from?
not the motor cortex as it is from old areas
where is the output of the UMN?
output to lower MN via interneurones
what is the role of UMN?
planning, initiating and directing movements
where do other UMN originate ?
other UMN originate in phylogenetically ancient motor centres of the brainstem - red and vestibular nuclei, superior colliculus reticular formation - regulate
how many UMN pathways are there are what are they?
what is common about them?
two pathways: direct and indirect
direct motor pathway - input to lower MNs from axons extending directly from cerebral cortex
indirect motor pathway - input to LMN from motor centres in brainstem
they both connect to the LMN
why do the UMN pathways both connect to the LMN?
because the LMN have a final common pathway
what does the basal ganglia do? and what does it connect to?
they provide input to the UMN and connects with the motor cortex
what is the role of the basal ganglia?
- helps initiate and terminate movements
- suppresses unwanted movements
- establishes normal level of toe in muscles
what is a disease in which the basal ganglia’s inhibited?
Giles de la Tourettes syndrome - they are unable to terminate movements that the rest of us can
what is the primary role of the cerebellum?
to step in and correct movement if it is not intended.
controls the activity of the UMN
how does the cerebellum connect to the cortex?
connects to the cortex via the thalamus and the brainstem
how does the cerebellum correct movement that is not intended?
it monitors movement for differences in intended and actual movements and if there are any discrepancies, it sends an error signal and tries to reduce the discrepancy
where is the cerebellum located?
at the base of the brain
what is the appearance of the cerebellum?
tight, intricate folds
what 3 things did the ‘Basic Circuitry’ 1967 describe?
the structure of each of the cell types in the cerebellum
their synapse connections
their electrophysiology
what is the name of the 4 parts of the cerebellum?
mossy fibre input
granule cells
purkinje cells
climbing fibres
what is the mossy fibre input part of and where is it from?
part of the WM underlying the cortex
from many different regions of the brain and spinal cord
what do mossy fibres synapse onto?
granule cells in the bottom (granular) layer
what is the proportion of mossy fibre input to granule cells?
granule cells outnumber mossy fibres 50:1
where do granule cells send their axons to?
to the top (molecular) layer where they split into two to produce parallel fibres
what do the parallel fibres of mossy fibres form?
synapses with purkinje cells
what is the name of the largest cel in the cerebellar cortex?
purkinje fibres
where are the cell bodies of purkinje cells?
in the middle (purkinje) layer
what is the purkinje cells main role?
to be the sole output cells of the cerebellar cortex
how many parallel fibre synapses do purkinje cells receive?
around 150,000
where do climbing fibres send their inputs?
a single climbing fibre input goes onto each purkinje cell
what are climbing fibres?
they are the axons of cellist the interior olive, at the base of the brainstem
what do the climbing fibres wrap around? and how many synapses does it form?
the purkinje cell dendritic tree
forms around 1000 synapses - all with the same input signal
what is a simple spike in terms of PC firing ?
it is when the PC fires spontaneously of usually about 5o spike/second
what can improve the firing rate of the PC cells?
parallel-fibre input can increase this rate to >200 spikes/sec
what is a complex spike?
very unusual shape
produced by climbing fibre input
why are complex spikes considered reliable?
because whenever climbing fibres fire, PC also fires
is there an increased or decreased frequency of firing in terms of complex spikes compared to simple spikes?
there is a decreased frequency of firing compared with simple spikes, so has a little effect on output
how does mossy fibre input contrast with climbing fibre input?
they are all wrapped around PC dendrites
acts as one enormous synapse
low frequency of firing
what do unusual circuits do for clinical and experimental observations?
for clinical and experimental observations of cerebellar dagga, can see that it does not cause paralysis but makes movements inaccurate, slow and un coordinated
-similar to the effects of alcohol
what is important to note about the cerebellums influence on moving the body?
cerebellar damage does not lead to paralysis
what is the importance of the fact that cerebellar damage does not lead to paralysis?
this means that other parts of the brain issue movements commands and may carry them out inaccurately
what s the role both the cerebellum?
to ensure movements are carried out properly
what was Brindley’s suggestion?
that the purpose of the cerebellum is to learn motor skills so that when they have been learned, a simple incomplete message can be sent from the cerebrum and will suffice to provoke the execution of the movement
what are the two models that have been made to explain the cerebellums role?
the Marr-Albus model
what does the Murr-Albus model suggest?
that to learn to make accurate movements, you must have information about what you did wrong an error signal
what component of the cerebellum conveys an error signal?
the climbing fibres
what do complex fibres change?
synaptic weight
what do complex fibres affect on the PC dendritic tree?
all the parallel-fibre synapses
what was the rule suggested to explain how complex fibres affect synaptic weight ?
synaptic weight s changed according to the correlation between the parallel fibres signal and the error signal conveyed by the climbing fibres
what is the suggested learning rule?
the de-correlation learning tule states that:
if there is a positive correlation between the parallel fibres signal and the error signal, the synaptic weight would be low
if there is a negative correlation between the parallel fibres signal and the error signal, the synaptic weight would be high
when does ‘learning’ stop?
when there is no longer a correlation between any parallel-fibre signal and the climbing fibre signal
where is there support for the de-correlation learning rule? explain it
in long term depression as a paired stimulation of parallel fibres with stimulation of climbing fibres, synapses with parallel fibres and PC become depressed.
this is consistent with the error signal idea which was that signals are positively correlated with climbing-fibre signals
what is the de-correlation learning rule a version of?
the mean square learning rule and thus is computationally powerful
what is the mean squared learning rule used mostly in?
widely used in signal processing( e.g. biomedical engineering, seismology etc)
what does the mean square learning rule support?
the cerebellum implements supervised learning
what kind of tests have been used to examine the proposed role of the cerebellum in motor learning?
simple motor learning tasks
what is the name of the reflex that is sed to stabilise eye movements?
the vestibule-ocular reflex (VOR)
describe the VOR
when the head rotates, the eyes move in the opposite direction. this keeps the visual world stable and can be mimicked by looking at a target and moving your head
why is VOR so important?
there is a problem when the eye moves relative to the world, the image moves across the retina which blurs vision. this means that visual information is irretrievably lost. this could be bad as you may not be able to see your predator/prey
when do we use VOR?
when we walk
our heads move and down
VOR counter-rotates eyes to keep visual image from moving
what are the learned changes in VOR reflex in monkeys?
eyes initially move too far but after some experience and gain of the VOR, it rests and the eyes move an appropriate distance in relation to head movements – compensating for the altered size of the visual image
what part of the cerebellar cortex is involved in VOR adaptation?
the flocculus
inactivation of this region prevents VOR adaptation
what things is the cerebellum thought to be involved in?
active sensing, sensory prediction and emotional&cognitive processing
what is the basic microcircuitry of the cortex like?
fairly uniform her the entire cerebellum but not identical. this suggests the there is a multiplicity of functions must arise from external connectivity cerebellar zones
how is the external wiring of the cerebellum connected to project to a unique set of neural targets?
PCs in a given parasagittal strip of cortex receive climbing fibre input from a unique region of the inferior olive
PCs in a given parasagittal strip of cortex project to a unique region of the deep cerebellar nuclei
this in turn project to a unique set of neural targets
what can be used to predict the sensory effects of the brain?
the de-correlation learning rule
why is it not possible to tickle yourself?
because the attenuating signal to tickle comes form the cerebellum and so the cerebellum is what is used to predict the sensory effects of tickling movements - then you would know about it therefore not feel it
how to predict the effects of head movements?
cerebellar tuut neurones have been found that respond to passive head movements but don’t respond to very similar active head movements. this can also be used
how can being able to predict own head movements be an advantage ?
be able to distinguish your head movements from movement thats coming from elsewhere
ability to develop a self identity
what is the most basic circuit in the cerebellar cortex?
input=mossy fibres. these synapse onto granule cells, whose axons synapse onto PC. PC provide the output of cerebellar cortex. PCs also receive climbing fibre inputs, which behave in a very unusual way
what does the basic circuitry of the cerebellum do?
climbing fibres copy error signals about movement inaccuracy. this adjusts the weight of the synapses between parallel fibres and PCs, thus altering PC output in a way that makes movements more accurate.
evidence from the adaptation of the VOR consistent with the theory
what are the external connections of cerebellar cortex?
each small region of cerebellar cortex has unique inputs and outputs. the cerebellum can influence a very wide range of neural structures, from spinal cord to many areas of cerebral cortex
how can the external connections of cerebellar cortex be used for sensory and cognitive functions recently proposed for the cerebellum?
the learning rule proposed for ensuring accurate movements can also be applied to other sensory and cognitive tasks, including the ability to predict the sensory effects of ones own movements
define proprioception
the ability to sense stimuli arising within the body regarding position, motion and equilibrium. even with a blind fold, he/she knows through proprioception if an arm is above the head/hanging by the side of the body
what does muscle control require?
excitation of a muscle by alpha motor neurones but also continued feedback of information from each muscle to the nervous system at each instant.
what information is sent to the brain when muscle control is requires?
muscle length which comes from the spindle
muscle tension and the rate of change of muscle tension development
where is information sent from motor neurones going to?
to spinal cord cerebellum and cortex
what creates action potentials in the axon?
Group 1 alpha terminal endings are anulospiral and wrapped the equator of both bag and nuclear chain intrafusal muscle fibres.
Pulling apart of these coils that initiates action potentials in the axon
what information does group 1a sensory endings relay?
Group 1 alpha sensory endings relay information on the dynamic phase of the muscle stretch
describe group 2 endings and what information do the sensory endings relay?
Group 2 ending have a ‘flower spray’ terminal ending embedded in the equatorial regions of the bag fibres – but have anulospiral endings largely confined to nuclear chain fibres
Group 2 sensory ending relay information on the static phase of the muscle stretch ie its final stretch
at what stage during the stretch is the only time that endings respond? when are they free?
Endings only respond during dynamic phase of stretch
Only free after final stretch is reach
what useful information does the CNS receive by viewing group 1 and 2 muscles together?
By viewing them together, CNS receives useful information on muscle activity:
Group 1: rapid burst of AP when muscle is stetching. Not much at static stretch
Group 2: steady state fire rapid Aps. Not much when dynamic stretch is happening
what is the problem with muscle spindles if there is no stretch?
they will be useless as Muscle spindles are only useful when they are under tension
If there is no stretch- no info will go to the brain
