week 8 - nervous system Flashcards
functions of frontal lobe
responsible for motor control and is involved with retention of long term memories
involved in determining mood and emotions
functions of parietal lobe
The parietal lobes can be divided into two functional regions. One involves sensation and perception and the other is concerned with integrating sensory input, primarily with the visual system. The first function integrates sensory information to form a single perception (cognition)
what separates the frontal and parietal lobes
central sulcus
functions of occipital lobe
it is the main visual cortex and is where dreams are developed and processed
functions of temporal lobe
responsible for hearing and interpretation of speech and hearing
functions of cerebellum
controls movement specifically coordinating movements
involved with maintenance of posture in space and maintenance of muscle tone
components of the brainstem
midbrain
pons
medulla oblongara
functions of brainstem
relay tract for motor and sensory systems
also where cranial nerves arise to supply motor and sensory innervation to face and neck
involved in controlling the cardio-respiratory systems
how many of each vertebrae do we have
cervical - 7 thoracic - 12 lumbar - 5 sacral - 5 fused coccyx - 3 to 5
what information passes through the dorsal root
sensory afferent fibres of spinal nerves
what information passes through the ventral root
motor efferent fibres leaving from the ventral gray horn
what is white matter primarily composed of
myelinated axons
what is grey matter primarily composed of
neurons (cell body, axons, dendrites) and supporting cells (glia)
what does the dorsal root ganglion contain
composed of the cell bodies of afferent neurons
what is a nerve plexus
a collection of nerves that supply specific body regions
what does the brachial plexus supply
goes on to provide motor and sensory innervation to the upper limb
spinal origin of brachial plexus
comes from C5 through to T1
sometimes there is a contribution from C4 and T2
what is a dermatome
area of skin innervated by the sensory fibres of a single spinal nerve
how many spinal nerves
31 pairs
clinical significance of dermatomes
can give an indication of the level of the spinal cord where damage may be
a lesion of just a single spinal nerve however would rarely give numbness over that area due to overlap of innervation
how many cranial nerves
12 pairs
name the cranial nerves and their functions
- Olfactory - smell
- Optic - vision
- Oculomotor – eye movements
- Trochlear – eye movements
- Trigeminal – motor to muscles of mastication and general sensory to the face
- Abducens – eye movements
- Facial – muscles of facial expression
- Vestibulocochlear – hearing and balance
- Glossopharyngeal – swallowing, taste
- Vagus – wandering nerve supplying heart, lungs, gut – reduces heart rate, reduces breathing, increases gut motility – nerve of rest and digest
- Spinal accessory – neck muscles
- Hypoglossal– muscles of the tongue
what do the cranial nerves supply
head and neck structures as well as the gut, heart and respiratory system
three meninges in order of deep to superficial
pia mater
arachnoid mater
dura mater
function of meninges
They provide a supportive and structural framework for the vasculature, and also protect the CNS from mechanical damage, aided by the cerebrospinal fluid
what is contained in the lateral ventricles
cerebrospinal fluid
where does venous blood from the brain drain to
dural venous sinuses and ultimately to the internal jugular veins
from what vertebral levels does the sympathetic nervous system arise
T1-L2
origins of the parasympathetic nervous system
cranial nerves III, VII, IX and X and S2-4
where does the spinal cord terminate in an adult
L2 approximately
what is the clinical relevance of the termination of the spinal cord at a higher
vertebral level
A sample of cerebrospinal fluid can be taken (to examine for infection eg meningitis) after the spinal cord terminates. Generally, this is taken from the space between L3/4 or L4/5 to ensure no damage is done to the spinal cord
function of corpus callosum
responsible for communication between the two cerebral hemispheres
hypothalamus function
responsible for homeostasis
thalamus function
primarily functions as a relay centre for fibres passing up to the brain and down to the rest of the body
regulation of consciousness and alertness
components of the peripheral NS
spinal and cranial nerves
what separates the 2 brain hemispheres
groove called the longitudinal fissure
what are the wrinkles on the brain
Brain is folded into gyri (ridges) and sulci (grooves in between) – helps increase surface area in the space limiting skull
what is the telencephalon
cerebrum
diencephalon components
thalamus and hypothalamus
mesencephalon
midbrain
what do the telencephalon and diencephalon make up
the forebrain
glial cells and their functions
astrocytes - involved in nutrient supply to neurons in CNS
microglia - defence role; phagocytic
ependymal cells - involved in production of CSF
oligodendrocytes - neuronal support and myelin formation in the CNS
schwann cells - neuronal support and myelin formation in the PNS
dendrite function
specialised to receive chemical signals from the axon termini of other neurons
Dendrites convert these signals into small electric impulses and transmit them inward, in the direction of the cell body
describe myelin
the layers of fatty tissue around an axon
protects, insulates and allows faster propagation of nerve impulse
describe the nodes of ranvier
gaps found within myelinated axons- they speed up propagation of action potentials along the axon
describe the central canal of the spinal cord
it is a hole in the middle of spinal cord and is surrounded by ependymal cells
what are denticulate ligaments
paired ribbon-like extensions of pia mater that attach to dura mater
what is the filum terminale
pia mater extensions that stabilise spinal cord
describe the point where the spinal cord ends
Conus medullaris is where the spinal cord ends – surrounded by lumbosacral roots collectively referred to as cauda equina – L1-L2
describe the cauda equina
Nerve rootlets comprised of L2-5
cauda equina sits in a space called the lumbar cistern which is a space formed by the subarachnoid space. It extends from the conus medullaris to S2
two layers of dura mater
periosteal and meningeal
which spinal nerve does not have a dermatome and why
C1 does not have a dorsal sensory root and so has no dermatome associated with it
it has a motor root which supplies neck and muscles
3 classifications of PNS nerves
pseudounipolar neuron
multipolar neuron
autonomic multi-polar neuron
describe a pseudounipolar neuron
has one extension from its cell body and it splits into 2 branches - one goes peripherally and the other centrally
describe a multipolar neuron
single axon and has many dendrites - typically motor neurons
describe an autonomic multi-polar neuron
there is a synapse between the presynaptic and postsynaptic neuron
comes from the lateral horn
variations of neuron
unipolar, bipolar and multipolar
what kind if neuron is a sensory neuron
unipolar
difference between grey and white matter
grey has more cell bodies, dendrites, axon termini, astrocytes and blood vessels
white has more axons (myelinated), glial cells (oligodendrocytes), blood vessels
name of a group of neurons
called a nucleus in the CNS and a ganglion in the PNS
what is a cortex
neurons that are organised into layers and are usually found on the surface of the CNS
functions of the dorsal and ventral horn
Within the gray matter the dorsal horn receives and processes sensory information from the dorsal roots, whereas the ventral horn is primarily a motor structure and contains the motor neurons whose axons project out via the ventral roots
location of CSF
it fills the ventricular system, a series of interconnected spaces within the brain, and the subarachnoid space directly surrounding the brain
what are subarachnoid cisterns
CSF circulates through the subarachnoid space surrounding brain and spinal cord. Regions where these spaces are expanded are called subarachnoid cisterns.
describe spinal cord tracts
bundles of nerve fibres that run up/down and can contain autonomic, sensory and motor fibres
types of spinal cord tracts
spinothalamic = ascending and sensory corticospinal = descending and motor
what are dural venous sinuses
spaces between the endosteal and meningeal layers of the dura
they contain venous blood that originates for the most part from the brain or cranial cavity
the sinuses contain an endothelial lining that is continuous into the veins that are connected to them
function of CSF
cushions brain against impact/movement and against its own weight
provides a stale chemical environment for the brain
allows nutrient and waste exchange between nervous tissue and blood
production of CSF
Most produced by choroid plexus in lateral and fourth ventricles
Resorbed into venous system via arachnoid granulations
structural features of the blood-brain barrier
restriction is at least partly due to the barrier action of the capillary endothelial cells of the CNS and the tight junctions between them
Astrocytes may also help limit the movement of certain substances
two parts of the human nervous system
somatic (we have active control over) and autonomic (we do not control)
which cortex’s does the frontal lobe contain
motor cortex - involved in planning and coordinating movement
prefrontal cortex - responsible for higher-level cognitive functioning
describe brocas area
region in the frontal lobe of the dominant hemisphere, usually the left, of the brain with functions linked to speech production
two parts of the ANS
central and peripheral
two parts to the peripheral NS
sympathetic and parasympathetic
function of the parasympathetic NS
responsible for the body’s rest and digestion response when the body is relaxed, resting, or feeding
it decreases respiration and heart rate and increases digestion
function of the sympathetic NS
it directs the body’s rapid involuntary response to dangerous or stressful situations
where do preganglionic neurons arise from (SNS)
lumbar and thoracic regions of spinal cord
describe the SNS process
preganglionic fibres go to sympathetic ganglia chain - some fibres synapse immediately, some travel up or down ganglia first and some pass through the chain without synapsing (synapse at collateral ganglia instead)
from ganglia, the postganglionic fibres run to target organs
where do preganglionic neurons arise from (parasympathetic NS)
brainstem and sacral region of spinal cord
describe the process of the PSNS
preganglionic neurons exit from cranial nerves and spinal cord
neurotransmitters in SNS
preganglionic neurons use acetylcholine
postganglionic neurons use noradrenaline except in sweat glands and deep muscle veins when it uses acetylcholine
types of receptors in the SNS and their functions
alpha 1 - causes arteriole constriction
alpha 2 - causes venous and coronary vasoconstriction
beta 1 - increases heart rate and increases contractility
beta 2 - causes smooth muscle relaxation
agonist
mimics the action of a recptor
antagonist
these oppose the action of a receptor
examples of alpha 1 agonist drugs
metaraminol
pseudoephedrine
phenylephrine
alpha 1 antagonist drug
doxazosin
alpha 2 agonist drugs
anti-erectile dysfunction drugs
b1 agonist drug
isoprenaline
b2 agonist drug
salbutamol
when are b2 antagonist drugs used
only in lab - no clinical use
actions of the PSNS
Pupillary constriction – improves near vision
Nasal engorgement – maximises sensory absorption
Excess salvation – aids digestion
Increased gastric secretions and blood flow
Slow heart rate down
Bronchoconstriction
Micturate, defecate and ejaculate
origin of SNS
thoracolumbar except for cervical ganglia
origin of PSNS
origin has two parts - cranial and sacral
Cranial is made of the 3rd, 7th, 9th and 10th nerves
Sacral is 2, 3, 4
neurotransmitter for PSNS
acetylcholine
3 ganglia associated with the vagus nerve
cervical, thoracic and coeliac ganglia
muscarinic receptors
G-coupled protein receptors involved in the parasympathetic nervous system
functions of the muscarinic receptors
M1 - affects arousal attention and emotional response
M2 - cardiac inhibition
M3 - lacrimal, salivary
M4 - direct regulatory action on K and Ca ion channels
M5 - may regulate dopamine release at terminals within the straitum
M1 agonist drug
xanomeline - potential treatment of alzheimers and schizophrenia
receptors of the PSNS
muscarinic and nicotinic receptors
describe nicotinic receptors
receptors that respond to acetylcholine
also respond to nicotine
B1 antagonist drugs
these bind to receptors and block it (beta blockers)
atenolol - lowers bp and heart rate
what does brainstem death lead to
paralysis and unconsciousness
apnoea
loss of cranial nerve function
coning of the brain process
pressure build up and causes a decrease in the blood flow
swelling of brain forces the brain through small opening at the base of skull where it meets the spinal cord
restricted blood supply to brainstem
brainstem blood supply
single blood vessel called basal artery
what condition is a result of damage to the basal artery
locked-in syndrome - can think and move eyes but cannot speak or move
brainstem death example tests
9th – spatula at back of throat and patient should gag
for 5th nerve – brush cotton wool against cornea – should cause blinking
test for oculomotor cranial nerve – opening eyes, shining light and looking for consensual reflexes
guided therapy
used in mild infections when you can wait a few days before treatment
allows best antibiotic to be selected
empirical therapy
used when a delay in therapy results in worsening of condition
prophylactic therapy
used when healthy people are exposed to surgery, injury or infected material
used in immunocompromised patients
preventing infection before it begins
types of antibiotic
bactericidal - directly kills bacteria and sterilises area
bacteriostatic - bacteria remain in medium but are dormant
example of bactericidal and bacteriostatic antibiotics
bactericidal - penicillin
bacteriostatic - clarithromycin
which classes of antibiotics target cell walls
penicillins and glycopeptides
classes of antibiotics that target ribosomes
macrolides
aminoglycosides
classes of antibiotics that target DNA
quinolones
classes of antibiotics that target metabolism
trimethoprim
what group of antibiotics do penicillins belong to
beta-lactum group
these drugs are chemically produced derivatives of naturally occurring beta-lactums
how do penicillins work
they target penicillin binding proteins which are present in or around peptidoglycan cell wall - penicillin inserts into binding site of penicillin binding proteins and prevents peptidoglycan synthesis
3 principal mechanisms of antibiotic resistance
mutation/modification of target site
inactivating enzymes
limit access eg. reduced permeability
how is resistance passed on in bacteria
genes mediating resistance can often easily be transferred – often found on plasmids which bacteria pass onto each other
what is adrenaline
a hormone produced by the adrenal glands in situations of acute stress
when is adrenaline produced
stimulation of SNS causes adrenal medulla to produce adrenaline
effects of adrenaline
increases heart rate and respiration
mobilises blood glucose stores
where is adrenal medulla derived from
embryonic neural crest cells
rest of adrenal gland is derived from mesoderm
adrenaline signalling process
adrenaline binds to and activates a g-protein coupled receptor
how do g-proteins work
g-proteins only active when bound to GTP
g-protein-coupled receptors use large heterotrimeric g-proteins
an activated g-protein activates downstream effector proteins
GTPase activating protein and regulators of g-protein signalling cause hydrolysis of GTP to GDP
effects of g-protein coupled receptor (GPCR) activation
alpha subunits in particular (but also beta and gamma) can target multiple different effector proteins when activated - can activate or inhibit targets directly or indirectly
some GPCRs work through producing second messenger molecules
describe adrenaline signalling and glucose release in muscle and liver cells
adrenaline binds to GPCR triggering activation of g-protein alpha subunit which activates adenylyl cyclase which produces cAMP
cAMP activates protein kinase A
this leads to glucose production and inhibition of glycogen synthesis
what 2 things does activated protein kinase A do
PKA phosphorylates and activates phosphorylase kinase which phosphorylates and activates the enzyme glycogen phosphorylase which catalyses breakdown of storage molecule glycogen, to produce glucose
PKA also phosphorylates and inhibits the enzyme glycogen synthase so glycogen synthesis cannot occur
switching the signal off (adrenaline signalling)
when adrenaline is no longer present, signalling process must be switched off
g-protein alpha subunit hydrolyses GTP to inactive GDP (cannot activate adenylyl cyclase so no new cAMP produced)
cAMP removed by phosphodiesterases
calcium ions acting as second messengers can be actively removed by using ion channel pumps
what is a nerve impulse
wave of altered charge across nerve cell membrane that sweeps along axon aka. Depolarisation or action potential
direction of travel for Na and K ions in a cell
sodium is the main EXTRAcellular ion - can diffuse into cell
potassium is the main INTRAcellular ion - can diffuse out of cell
sodium potassium pump actively pumps out 3 Na ions and takes in 2 K ions
refractory period
time following action potential when no new AP can be initiated in same area of the membrane - blocks action potential travelling backwards
two segments of the refractory period
absolute RF - sodium channels that caused initial depolarisation are closed and cannot be activated
relative RF - sodium channels can work but because it would be starting from a hyperpolarised -90mV, it is hard to reach the threshold voltage for an AP
when do the different channels open
voltage-gated – changes in membrane potential
ligand-gated – specific ligand binding to receptor
mechanically-gated – tension in membrane
leakage – opens randomly – only channels open at rest
why is the resting potential of a neuron negative (less positive)
more Na+ ions outside the cell than K+ ions in cell
sodium/potassium pump uses energy from hydrolysis of ATP to pump 3 Na+ out and 2 K+ into cell
ions can pass through membrane through leakage channels - membrane is more permeable to K+ than Na+
describe myelin (on a neuron)
fatty substance that insulates a neuron, blocking depolarisation
current travels through the myelinated stretches of a neuron and depolarises the membrane only at the nodes of ranvier – myelin increases the speed of transmission
how can an action potential be triggered in a neuron
some stimuli can directly activate the nerve cell
or
a neurotransmitter from a nearby neuron can bind to a receptor on the nerve cell - receptor activation causes ion movement that triggers an AP in first neuron
excitatory pre-synaptic potenitals
inputs that increase plasma membrane potential making it more likely that the threshold voltage will be met and an action potential generated
inhibitory pre-synaptic potentials
decrease plasma membrane potential making it less likely that the threshold voltage will be met and an action potential generated
describe the two types of summation
spatial - summation of inputs from different areas such as from different dendrites
temporal - same input occurs multiple times within a short time period - not enough time for the change in potential that was caused by first wave to fall/rise bacl to resting potential before second wave of input hits - with an excitory input, threshold voltage for AP can be reached quicker
what are synapses made of
a presyntaptic nerve axon terminus and a postsynaptic nerve dendrite with a gap (synaptic cleft) between
neurotransmitters
(bio)chemical signals that neurons use to cross the synaptic cleft
describe signalling across the synapse with a neurotransmitter
released when AP reaches presynaptic neuron termini, then it diffuses across the synaptic gap
binds to receptors on dendrites of postsynaptic neuron
different NTs associated with different nervous system functions
NT can be excitatory or inhibitory
chemical classifications of NTs
amino-acids and derivatives - e.g. glutamate and GABA
catecholamine (monoamines) - derived from Tyr eg. dopamine, serotonin
acetylcholine - derived from choline
peptides eg. substance P, endorphins
where is glutamate found
main excitatory NT in CNS
where is GABA found
main inhibitory NT in CNS
GABA signalling process
GABA binds to GABA-A receptor which is an ion channel - binding causes conformational change that opens chloride ion channel
ions move through channel along conc. gradient
GABA released from presynaptic neuron into synapse - diffuses across cleft and binds to GABA-A receptor in post-synaptic neuron membrane
Neurotransmitters can be removed from synapse:
Reuptake of neurotransmitter through specific reuptake transporters
Presence of specific enzymes which chemically degrade the NTs
signalling pathway for acetylcholine at NMJ
AP travels down axon, Ach released from axon termini and diffuses across gap, binds to the nicotinic Ach receptor (sodium ion channel receptor) on postsynaptic muscle cell membrane (motor end plate)
difference between introns and exons
exons – kept when coding for proteins
introns – do not take part in translation
why is the protein coding region smaller than the RNA coding regio
some of the RNA is not translated and instead can be either a cap addition site (adds a protective nucleotide on the end of mRNA) or a polyA addition site which adds lots of nucleotides to protect the end of the mRNA
describe the 3 steps of transcription
Initiation: RNA polymerase II comes to the start of gene, DNA strands pulled apart
Elongation: RNA gets longer and it forms a transcription bubble
Termination: RNA synthesis stops
processing of primary mRNA
Primary RNA transcript includes introns
Processing occurs in nucleus
RNA splicing is the removal of introns by spliceosome
mRNA has a cap and polyA tail – exported to cytoplasm for translation
what are transcription factors and what do they do
proteins that bind very tightly to short and very specific sequences of DNA to affect the rate of transcription (positively or negatively)
determine how much protein is made from each gene
examples of transcription factors
p53 and E2F in cell cycle
nuclear hormone receptors (ligand dependant transcription factors) -
glucocorticoid receptor, oestrogen receptor, testosterone receptor, retinoic acid receptors
how is transcription initiated
a transcription initiation complex (TIC) needed
RNA II polymerase cannot bind directly to DNA so general or basal transcription factors act as bridge - these TFs bind to sequences of DNA called the TATA box and are usually found slightly before the start sites for transcription
promoters are sequences of DNA that proteins initiating transcription bind to
TFs on upstream enhancer elements further stabilise TIC
disease from mutation CCR5 promoter
affects rate that HIV progresses to AIDS
mutations in factor IX promoter lead to
haemophilia B
what regulates transcription
enhancers and silencers
these are DNA sequences where transcription factors bind to affect rate of transcription
enhancers make it more likely that promoter will be activated, silencers make it less likely
example of activators in gene expression
p53 - activator of transcription of p21 causing cell cycle arrest and DNA repair
E2F - activator of transcription of genes needed for S phase
examples of repressors in gene expression
p53 - repressor of transcription of survivin causing apoptosis
Oct-1 - repressor of transcription of thyroid stimulating hormone in all cells apart from thyrotrophs in the pituitary
how does DNA being closed regulate gene expression
nucleosomes keep DNA closed meaning the DNA is not accessible to TFs
super enhancers called locus regions can open chromatin spanning several genes
examples of constitutive genes
beta-actin (microfilaments)
ribosomal proteins
general/basal TFs
what are constitutive genes
Constitutive genes = housekeeping genes
have a constitutive promoter
what are inducible genes
genes which are only expressed in certain tissues or cells and are only expressed at certain times
examples of inducible genes
cell specific -CD4, CD8, collagen 1 and 2, globin, myelin
time specific - cyclins, melatonin, inflammatory cytokines
describe alternative splicing
Exons stay in the same order but different exons are used to make different mRNAs and proteins from same gene
clinical relevance of the genome
can look at genome and check whether they are expressing a normal protein or a mutated version
clinical relevance of the transcriptome
can identify signalling pathways acting in the cell/tissue
can differentiate between different diseases
clinical relevance of the proteome
can be profiled and used for diagnosis, prognosis and treatment selection
