The Nervous System Flashcards
what makes up the neuronal microenvironment?
- glia
- capillaries
- neurons
- extracellular space
what is the extracellular space comprised of?
- extracellular matrix (ECM): solid part including collagen and molecules to form a scaffold
- Brain extracellular fluid (BECF): fills in gaps within the ECM
(BECF is distinguished from the ECF that is found in parts of the ventricular system)
how do neurons and the BECF influence each other?
- when a neuron increases in activity, it changes the composition of BECF
- changes in BECF composition influences the activity of the neuron
positive feedback loop
what could happen if the positive feedback loop between BECF and neurons is uncontrolled?
- neuronal dysfunction and neuronal cell death
therefore BECF composition must be tightly regulated
how could BECF composition be affected by increased neuronal activity?
- increased K+ conc
- changes in Ca2+ conc
- changes in O2, glucose and CO2 conc
- increased H+ so acidification
- change in neurotransmitter conc
how could a change in BECF composition change neuronal activity?
- increased K+ in BECF could elevate resting potential, bringing the membrane closer to threshold for AP firing
- increased neurotransmitter release could lead to unspecific activation and neuronal activity
what 4 components regulate the neuronal microenvironment?
- Blood brain barrier (BBB)
- cerebrospinal fluid (CSF) in ventricular system
- neurons
- glial cells (astrocytes)
how was the BBB identified?
intravenous injection of dyes into systemic circulation:
- dyes pass across leaky capillaries
- dye stains soft tissues and spinal cord
- no staining seen in the brain, so lining of blood vessels in brain must be tighter (no leaks)
what is the function of the BBB?
- protect neurons from fluctuations in concs of substrates from the blood
- e.g. increased amino acid conc after a meal could cause activation of receptors to excite/inhibit neurons
- e.g. increases in K+ and H+ after exercise
- e.g. changes in hormone concs and inflammatory mediator concs
how is the BBB maintained?
- tight junctions between endothelial cells of capillaries (no fenestra)
- everything in the BBB must be selectively moved out transcellularly
- thick basement membrane
- astrocytic endfeet form tight junctions to facilitate transport between BECF and blood
how do important molecules get through the BBB?
- facilitated transport: Glut1
- exchangers: Na-H exchanger
- cotransporters: Na-K-Cl cotransporter
- small, nonpolar, lipid soluble molecules can pass through e.g. CO2, O2, nicotine, heroin, caffeine
specificity of BBB makes treating neuronal diseases difficult as its hard for drugs to enter brain
what are the leaky regions of the BBB?
- choroid plexuses in the ventricular system
- circumventricular organs which surround the ventricles
ependymal cells beneath these areaa have leaky tight junctions
why are there leaky regions in the BBB?
- to sense/release hormones from/into the blood e.g. hypothalamus or pituitary
- osmoreceptors e.g. OVLT and SFO in hypothalamus
- temperature control centres and fever: cytokines detected in OVLT
what is the flow of CSF?
- secreted from choroid plexus and foramens
- flows from lateral ventricles, to third ventricle, to superior sagittal sinus (SSS)
- circulates around central canal
- absorbed from subarachnoid space (SAS) into the venous blood system at the SSS
what is the volume of CSF in total?
150ml:
- 30ml in ventricles
- 120ml in SAS
what does CSF achieve?
- reduces effective weight of the brain from 1400g to <50g
- decreases risk of accelerating/decelerating injuries
how is CSF secreted?
- 500ml CSF produced per day and replaced 3x per day (30% made by capillaries)
- ultrafiltration of plasma into ECF across leaky capillaries
- selective absorption of substances into CSF across choroidal epithelial cells
- free movement of substances from CSF to BECF across ependymal cells
what is the function of the epithelial ependymal lining?
separates brain tissue from ventricular system:
- ependymal cells are leaky to CSF can move into brain
- cavity in ventricles separates ECF solution from CSF by tight junctions of the choroidal epithelium
- leaky capillaries allow ultrafiltration from plasma into the ECF
the CSF is protected from the filtered ECF by tight junctions of the choroidal epithelium
what is the CSF comprised of?
- potassium: lower in CSF than in the plasma
- amino acids: lower in CSF than in the plasma
what are meniniges?
- membranes around the outside of the brain and spinal cord
- three different types work together to protect the brain from solutions
- the three types vary in permeability and structural support
what are the 3 meninges?
leptomeninges?
- Pia mater (inner most)
- thin, permeable so allows movement to and from BECF and CSF in the SAS
- covers brain surface and blood vessels and allows diffusion between CSF and BECF - Arachnoid mater: separated from pia mater by CSF in the SAS
- arachnoid mater pokes through the dura mater and into the sinus
- how CSF gets absorbed from SAS into SSS and venous system
- has tight junctions so harder for fluid to move across
Dura mater: toughest
- one layer follows the gyri and sulci, arachnoid mater and pia mater
- the outer layer surrounds the brain in circular fashion
What are the evaginations of the arachnoid membrane?
- arachnoid granulations (up to 1cm)
- arachnoid villi - both project through the dura mater and into the SSS
How is CSF absorbed? why is it absorbed?
arachnoid mater is joined by tight junctions:
- increased pressure of CSF causes a bulk absorption of CSF by the arachnoid villus in a vesicle
- vesicle fuses with membrane on basolateral side and out into the venous sinus
increased intracranial pressure is caused by constant production of CSF at choroid plexus, so if it isn’t removed, CSF volume would just keep expanding
where does exchange of CSF and BECF occur?
- From the ventricles across ependymal cells as there are no tight junctions here
- movement of CSF in lateral ventricles into BECF
- movement of BECF back into CSF - From SAS across the pia mater as there are no tight junctions here
- exchange of CSF from SAS into BECF
- vice versa
what is exchanged from CSF to BECF?
- macronutrients e.g. glucose
- micronutrients e.g. vitamins
- ions e.g. bicarbonate
what is exchanged from BECF to CSF?
- metabolic waste products e.g. CO2
- neurotransmitters
What happens if CSF cannot circulate properly?
Hydrocephalus: a blockage along the ventricular system in the cerebral aqueduct
- anything above the third ventricle will keep expanding due to excessive CSF production
- puts pressure on brain tissue, leading to necrosis in the brain, loss of brainstem reflexes (e.g. heart rate + respiration)
- can be fatal
How do neurons and astrocytes clear neurotransmitter from the BECF?
neurons
- take glutamate back up by EAAT3 into the presynaptic terminal
astrocytes:
- contain EEAT1 and EEAT2 that moves glutamate from BECF into the astrocyte
- astrocyte breaks down glutamate into glutamine and recycles it back to presynaptic terminal to be reformed as glutamate and reused
why is clearing and recycling of neurotransmitter important?
- if glutamate isn’t removed, there will be unspecific, overactivation of signals
- ensures not to waste neurotransmitter through recycling by EAATs into neurons and astrocytes
how do neurons and astrocytes remove K+ from extracellular space?
- Na-K ATPase moves Na+ out from intracellular to extracellular compartment to maintain low intracellular Na+
- ATPase moves K+ from ECF back into cell to maintain low extracellular K+
- ensures membrane potential doesn’t increase as extracellular potassium increases
how do increases in extracellular K+ affect astrocyte function?
- increase glucose metabolism
- enables production of ATP to drive Na-K ATPase so more K+ can be taken up by astrocyte - increased K+ uptake
- increase in intracellular K+ conc drives an increase in glucose metabolism
what are the equilibrium potentials and resting potentials of neurons and glia?
equilibrium potential for K+ in both neurons and glia is -90mV
neurons have resting membrane potential of -65mV
glia have resting membrane potential of -85mV
how does extracellular K+ influence astrocytes?
- neuronal membranes are more permeable to Na+ than astrocytic membranes
- this causes neuronal membranes to have a less negative resting potential then astrocytic
- astrocytes have higher K+ selectivity than neurons so are more sensitive to extracellular K+ changes
- so K+ has greater influence on astrocytic membrane potential
what does the astrocytic syncytium allow?
spatial buffering: regulation of extracellular potassium
how does the astrocytic syncytium allow spatial buffering?
- gap junctions (electical synapse) allow redistribution of K+ to areas of decreased activity
- if extracellular potassium gets too high, K+ moves into neighbouring astrocytes via gap junctions from high conc to low conc
what are gap junctions?
- made of connexins which form a connexon
- connexon forms a pathway to an adjacent astrocyte by joining to the connexon of that astrocyte
- allows free movement from one intracellular space to the other, without coming into contact with extracellular space
what is neurovascular coupling?
- joining of activity of neurons to vasculature blood supply of the brain
- astrocytes contact arterioles
- increase in neuronal firing rate causes increase in Ca2+ in the astrocyte which moves through syncytium
- this triggers release of vasoactive substances from astrocyte
- vasoactive substances act on arterioles to cause vasodilation and increase blood supply to astrocytes
- astrocyte is supplied with glucose and amino acids
What is MRI?
Magnetic Resonance Imaging:
- allows 3D structural images of the brain
- doesn’t allow visualisation of brain activities
which two techniques detect activity in the brain? how do they do this?
Positron Emission Tomography (PET)
- exploits glucose use
Functional Magnetic Resonance Imaging (fMRI)
- exploits oxygen use
active neurons need more glucose and oxygen, so more blood is directed to these neurons
- these two techniques detect the subsequent changes in blood flow
how does fMRI work?
- uses an electromagnetic wave to disrupt hydrogen atom
- non-invasive
- spatial resolution = 2-3mm
- temporal resolution = a few seconds
- oxyhaemoglobin and deoxyhaemoglobin distort the magnetic resonance properties of hydrogen atoms differently
what area in the brain lights up when playing tennis?
premotor cortex
what area in the brain lights up when remembering walking around your house?
parahippocampal gyrus
what does the nervous system develop from?
the neural plate of the ectoderm
what happens during neurulation? (around 22 days old)
- neural plate develops neural grooves and folds dorsally at the top
- groves deepen and folds become more dorsal
- neural grooves and folds divide into:
1. neural tube (CNS) and ventricular system
2. neural crest (PNS neurons)
these fuse dorsallt
how long does neurulation take?
6 days, from a flat plate to a tube
what do somites from the mesoderm form?
- vertebrae
- skeletal muscles -> any neurons that innervate skeletal muscle are called somatic neurons
what does the neural crest form?
neurons of the PNS:
- sensory neurons: cell bodies in the dorsal root ganglia
- autonomic neurons: e.g. postganglionic parasympathetic neurons
also chromaffin cells and schwann cells
why are women advised to take folic acid when pregnant?
- folic acid reduces chance of neural tube defects by 90% by influencing DNA synthesis to aid development
closing of the neural tube happens first centrally, and then up and down from the centre
what is anencephaly?
- defect in neural tube where it closes rostrally (where the brain develops)
- fatal
what is spina bifida?
-defect in the neural tube where it closes caudally (where the spinal cord develops)
what are the 3 primary brain vesicles from rostral to caudal?
- prosencephalon (forebrain)
- mesencephalon (midbrain)
- rhombencephalon (hindbrain)
what are the secondary vesicles of the forebrain?
- telencephalic vesicles (become cerebral hemispheres and move posteriorly and laterally)
- diencephalon
- optic vesicles: optic stalk and optic cup
what do the optic stalk and optic cup develop into?
optic stalk -> optic nerve (composed of axons and retinal ganglion neurons)
optic cup -> retina
what happens to the forebrain as it develops?
- it moves posteriorly and laterally
what are the main divisions of the forebrain?
telencephalon: cerebral hemispheres
- cerebral cortex, subcortical white matter (commissural, association, and projection fibers) and basal nuclei
diencephalon:
- thalamus, hypothalamus, basal telencephalon
- connects the midbrain to the forebrain
what white matter makes up the forebrain?
- corpus callosum (joins the two cerebral hemispheres)
- cortical white matter
- internal capsule
which ventricles are in the forebrain?
- lateral ventricles
- third ventricle
what is the midbrain differentiation from dorsal to ventral?
- tectum - connects to premotor centres to make rapid behavioural decisions
- cerebral aqueduct - allows flow of CSF from 3rd to 4th ventricle
- tegmentum - reticular formation involved in arousal, consciousness, sleep-wake cycles, coordination of certain movements, and cardiovascular control
what makes up the rostral part of the midbrain?
- cerebral aqueduct
- tectum splits to superior colliculus (and inferior) which is involved in vision
- periaqueductal gray involved in pain
- substantia nigra - voluntary movement
- red nucleus - voluntary movement
what makes up the caudal part of the midbrain?
- inferior colliculus - auditory
what makes up the rostral part of the hindbrain?
- rhombic lips - move dorsally to form the cerebellum
- fourth ventricle
- pons - generating breathing rhythm
- cerebellum - motor coordination, balance and posture
what makes up the caudal part of the hindbrain?
- fourth ventricle
- medulla - regulates cardiovascular and respiratory system
- medullary pyramids - form ventrally and allow white matter tracts up and down to spinal cord
what is the structure of the cerebellum?
- 2 hemispheres
- vermis in centre
- folia of the cerebellum increase SA for more neuronal input
what is special about the cerebellar cortex inputs?
- for every one neuronal output, thee are 40 neuronal inputs into Pukrinje dendritic trees
what do deep cerebellar nuclei do?
send out signals from cerebellar cortex
what do pontine nuclei do?
- project white matter nuclei into the cerebellar cortex
what is the function of the cerebellum?
- Coordination of movement, balance, posture
- 10% CNS volume: 50% CNS neurons
- Vestibulocerebellum - oldest - balance
- Spinocerebellum - muscle stretch receptors
- Cerebrocerebellum - projections from sensorimotor cortex - motor coordination
what are the 3 types of cerebral cortex?
- neocortex: around edge of brain (1-4.5mm)
- centre for higher brain functions, such as perception, decision-making and language - hippocampus - memory
- olfactory cortex: receives direct sensory info from olfactory bulb
- oldest type of bulb
- sense of smell
what is a gyrus and a sulcus?
gyrus = outward fold
sulcus = inward fold
what is the hippocampus and its structure?
- involved in memory by strengthening and weakening synapses
- found in each temporal lobe
- has 3 layers
- only place where neurons can be created in adulthood
what are the 4 lobes of the neocortex?
- frontal lobe
- parietal lobe
- occipital lobe
- temporal lobe
each lobe has different functions associated in different areas
the association cortex is any part of the lobes that doesn.t have a specific function, but still integrates sensory info
how do gyri and sulci distinguish different lobes?
- sylvian fissure separates temporal lobe from parietal and frontal
- central sulcus separates frontal lobe from parietal lobe
- parietal-occipital sulcus separates parietal and occipital
- precentral gyrus and postcentral gyrus are located either side of the central sulcus
What are the structural layers of the neocortex?
6 layers:
- Molecular layer - outer most
- nearest to pia mater
- contains lots of dendrites and axons, but no cell bodies - EGL - smaller neurons with smaller dendritic processes
- external pyramidal layer - trangular cell body shaped neurons
- IGL - larger neurons
- internal pyramidal layer - large pyramidal motor neurons that project down spinal cord
- fusiform neurons - small neurons which don’t project outside of CNS
how can the neocortex layers be distinguished by staining?
- Golgi stain: shows structure of single neurons
- Toluidine blue stain: stains cell bodies but not processes
- Wiegert-PAL: stains for myelin
why are some layers of the cortex varied in space and neuron size?
- the thickness of the neocortex and size of its neurons depends on its specific function
how was the neocortex mapped?
Brodmann’s cytoarchitectual map:
- he distinguished different numbered areas with different neocortical structures
- identified that each area had a different function e.g. touch in the postcentral gyrus of parietal lobe
- he stimulated areas of the skin and mapped onto the postcentral gyrus by recording nodes on the somatosensory cortex
- could use legions - stroke could cause certain part of the brain to stop working
how can the neocortex be mapped non-invasively?
- Positron emission tomography (PET)
- fMRI
- electroencephalography (EEG): electrodes placed around the brain to record different areas/activity
what is the lateral part of the neocortex made up of?
- motor cortex in precentral gyrus at back of frontal lobe, contains upper motor neurons
- somatosensory cortex in postcentral gyrus in front of parietal lobe
- primary visual cortex at back of occiptial lobe
- auditory cortex on central fissure
- rest of cortex = association cortex
what is the medial part of the neocortex made up of?
- the limbic lobe involved in complex behaviour
- hippocampus
- located in cingulate gyrus
what are the hidden areas of the neocortex?
the insula cortex:
- inside the temporal lobe
- sensorimotor processing
- emotional regulation
what does the basal forebrain consist of?
- basal ganglia
- involved in initiation of movement, motor control
- damaged in Parkinsons - amygdala
- involved in fear and emotion
what are the 3 white matter fibres?
- commissural fibres: project through corpus collosum and connect between hemispheres
- projection fibres: project through internal capsule link cortex to non-cortical areas via thalamus
- association fibres: link cortex areas within a hemispheres together
what is the thalamus and its function?
- formed from diencephalon
- over 50 nuclei
- relay station for in and out of the cortex and processes information
- connects neocortex via projection fibres
- aids basal ganglia in initiation of movement
what is the hypothalamus and its function?
- formed from diencephalon
- 11 major nuclei
- regulates homeostasis
- stimulates hormone release from pituitary
- controls pons and medulla for ANS
- surrounds 3rd ventricle
Can be split:
- laterally: close to outside of brain
- medially: close to midline
- periventricularly: region adjacent to 3rd ventricle
what is homeostasis?
maintenance of an internal steady state:
- disruption of a vital parameter
- sensory input to CNS
- contextual inputs from association cortex
- integration by hypothalamus
- acts via ANS, neuroendocrine system, or a behavioural change
- restoration of vital parameter within physiological range
what are the main nuclei of the hypothalamus?
- paraventricular nucleus: coordinates ANS and neuroendocrine response
- supraoptic nucleus
- Adenohypophysis (anterior pituitary)
- Neurohypophysis (posterior pituitary)
what is the action of the adenohypophysis?
- parvocellular neurons release neurohormones (releasing hormones) to the adenohypophysis
- the neurohormones travel through portal vein and activate receptors on troph cells which then release hormones into circulation
parvocellular have small diameter
what is the action of neurohypophysis?
- release hormones from the magnocellular neurons directly into systemic circulation
magnocellular have large diameter
what are the major anterior pituitary hormones?
tropic hormones: stimulate releaae/effects on other hormones
- growth hormone effects bone growth
- thyroid-stimulating hormone stimulates release of thyroid hormone
prolactin (PRL): lactation in mammary glands
what are the major posterior pituitary hormones?
ADH/Vasopressin: fluid balance
Oxytocin: parturition and lactation
what are the two efferent pathways of the ANS?
- Sympathetic (fight of flight): increase heart rate, relax airways
- parasympathetic (rest and digest): maintain steady HR and stimulate digestion, diuresis
both innervate the same effector tissues: smooth muscle, cardiac muscle, glands
they have opposing effects
can the ANS function without the hypothalamus?
Yes - through 4 major divisions:
- afferent division
- sensory receptors in internal organs, blood vessels, skin, visceral nerves - Brainstem nuclei
- e.g. cardiac nucleus, vasomotor control, respiratory nuclei - Efferent difvision
- sympathetic and parasympathetic nerves - effectors
- smooth muscle, cardiac muscle, glands, brown adipocytes
what is the general organisation of the ANS?
- preganglionic neurons - located in brainstem and spinal cord
- postganglionic neurons - cell bodies found in PNS in sympathetic/parasympathetic ganglia
- preganglionic neurons innervate postganglionic neurons via cholinergic synapses. ACh binds to nAChR, leading to depolarisation in postganglionic neuron
- postganglionic sends AP to effector cells
what is the sympathetic organisation?
- sympathetic cholinergic preganglionic neurons run down intermediolateral (IML) cell column from T1 to L3
- dorsal horn is where sensory input enters
- ventral horn is where somatic motor neurons are located
- dorsal root and ventral root join to form peripheral nerve
what is the process of sympathetic innervation?
- preganglionic neurons of IML exit ventral horn via ventral root
- preganglionic neuron enters sympathetic chain of ganglia that run along T1 to L3
- cholinergic synapse of the preganglionic neuron innervates an adrenergic postganglionic neuron with releases NA
- NA acts on alpha/beta adrenergic receptors on effectors
what controls the sympathetic preganglionic neurons?
Nucleus Tractus Solitarii (NTS)
- controls sympathetic outflow from spinal cord
- located in ventrolateral medulla
how was the NTS discovered to be in control of sympathetic preganglionic neurons?
- a recording electode was put in the IML, and a stimulating electrode in the medulla
- different parts of the medulla were stimulated to find which area communicated with IML cells
- an electrical current was sent through the electrode to excite medulla neurons and induce an AP, resulting in active IML cells
- stimulation of the ventrolateral area (NTS) of the medulla caused responses in the IML
- therefore NTS controlled sympathetic preganglionic neurons
what is the sacral organisation of the parasympathetic system?
- dorsal horn expands laterally and contains motor neurons which project past the ventral horn
- cholinergic preganglionic neurons synapse to cholinergic postganglionic neurons with nAChRs
- postganglionic neurons synapse to mAChRs on effectors
what is the cranial organisation of the parasympathetic system?
midbrain:
- Edinger-Westphal nucleus contains oculomotor nerve (CN III) which controls pupil dilation (doesn’t need hypothalamic control)
medulla:
- dorsal motor nucleus of the vagus (CN X) - nucleus ambiguous
why is the Vagus nerve important?
- carries ~80% parasympathetic outflow
- carries tonnes of visceral afferents for vagal nerve stimulation
