Theme 1: Fundamental Neuroscience and the Brain Flashcards
What are the 5 ways we study the brain?
Structure, Function, Connectivity, Trans-cranial Magnetic Stimulation/Temporary Lesion, Brain-Machine Interface
What are the 4 things a neuron must be able to do with neurotransmitters?
Synthesis, Storage, Release, Recovery and Degradation
Where can synapses be located?
Axodendritic, Axosomatic, Axoaxonic
What is the synaptic button?
a
What are the components of a chemical synapse?
Synaptic Button, Cytoskeleton, Mitochondria, Synaptic Vesicles, Active Zone, Synaptic Cleft
What is the Active Zone of a chemical synapse?
b
How large is the synaptic cleft?
20-50 nm wide
What does structure say about the synapse?
The presence of many mitochondria suggests the chemical synapse is a very energy hungry process needing a lot of ATP.
How do chemical signals get transmitted?
Vesicles fuse with postsynaptic membrane in synaptic cleft, releasing neurotransmitters into the postsynaptic neuron or muscle fibre (motor-end plate).
What can be the result of a synaptic transmission?
Direct excitatory (depolarised membrane) or inhibitory (hyperpolarised) neurotransmission, or Neuromodulation
What is Neuromodulation?
An alteration of the presynaptic cell’s ability to release more neurotransmitter or the postsynaptic cell’s ability to respond, usually by neurotransmitters
Name the 4 criteria defining a neurotransmitter
synthesized in neuron, present in presynaptic terminal and released in amounts sufficient to exert a defined effect on the postsynaptic neuron or effector organ, when administered exogenously mimics the action of the endogenously released transmitter, a specific mechanism exists for removing it from the synaptic cleft
What are the 2 categories of neurotransmitters?
Small-molecule neurotransmitters synthesized in the axon terminal (eg ACh) and larger Neuropeptides made in cell body.
What do the neural crest cells differentiate into?
(1) neurons and glia, (2)adrenal gland, (3) epidermis (4) skeletal and connective tissue of head
What are the layers of the neural tube?
lumen, ependymal layer, mantle layer, neural crest cells, ectoderm
What does the mantle layer of the neural tube become?
brain parenchyma
What does the ependymal layer of the neural tube do?
lines ventricles and central canal of spinal cord
What does the lumen of the neural tube become?
becomes ventricles and central canal
What are some neural tube defects?
Anencephaly 1 per thousand pregnancies (fatal failure of neural tube to zipper up at head), Spina Bifida 1 per thousand (25% morbidity, leads to open spinal canal)
What can help prevent neural tube defects?
Folic acid during pregnancy
What are the primary vesicles?
Prosencephalon (forebrain), mesencephalon (midbrain), rhombencephalon (hindbrain)
What are the secondary vesicles of the prosencephalon?
Telencephalon (cerebral hemispheres) and Optic Vesicles (eyes)
What are the secondary vesicles of the mesencephalon?
Diencephalon = thalamus/hypothalamus
What are the secondary vesicles of the rhombencephalon?
Metencephalon (pons and cerebellum) and Myelencephalon (medulla)
What does the mid-brain develop from?
mesencephalon
What are gray and white matter?
Gray matter is neuronal cell bodies (eg cerebral cortex, brain nuclei) and white matter is mainly myelinated axons.
What makes up the telencephalon?
Cerebral hemispheres/cerebral cortex, components of the limbic system, and the basal ganglia
Name the lobes of the cerebral hemispheres and their relative locations
Frontal (anterior), parietal (superior), occipital (posterior), temporal (lateral)
Name the major gyri and sulci and functions
Precentral gyrus (motor), postcentral gyrus (sensory), central sulcus (dividdes frontal and parietal lobes), lateral sulcus (divides temporal and parietal lobes),
List the sensory cortexes and locations
Somatosensory cortex (postcentral gyrus), visual cortex (occipital lobe), auditory, olfactory, gustatory cortexes (see diagram)
What is the white matter tract linking cerebral hemispheres?
Corpus Callosum
What are the parts of the corpus callousm?
Genu, Body, Splenium
Name two deep brain structures and their functions
Limbic systems (involved with emotion and memory), Basal Ganglia (involved in control of posture and voluntary movement)
How many ganglia are there in the cervical sympathetic trunk?
3: superior/middle/inferior, (stellate ganglia in some people = fused inferior cervical and T1 ganglia)
Where do postganglionic cervical sympathetic fibres exit and where do they lead?
(1) grey rami communications to spinal nerves (upper limbs) (2) piggy back down common carotid artery to heart (3) piggy back up internal/external carotid artery to head
What does the sympathetic supply to the head innervate?
Internal carotid plexus: to eye (dilates pupil, smooth muscle) and lacrimal gland (viscous secretions). External carotid plexus to submandibular and parotid gland glands (viscous secretions)
What is disruption of the sympathetic supply to head? What symptoms would they have?
Horner’s Syndrome - lesions anywhere from hypothalamus to preganglionic neurons. Pupil constricted/miosis, drooping eyelid/ptosis, lack of sweat on skin of face/anhydrosis
How many thoracic sympathetic ganglia? Where do they exit?
12 ganglia. Preganglionic fibres exit via thoracic splanchic nerves to abdomen. Postganglionic fibres exit via grey rami communicans to spinal nerves AND medial branches to heart/lungs
What do preganglionic thoracic fibres eventually split into?
Greater, Lesser, and Least thoracic splanchnic nerves
Where do the thoracic splanchnic nerves supply and what ganglia do they form?
Celiac ganglia for upper gut, superior mesenteric ganglia for mid gut, and aorticorenal ganglia for kidney. All sit around descending aorta.
How many lumbar sympathetic trunk ganglia are there and where do they exit?
- Postganglionic fibres exit via grey rami communicans to spinal nerves. Preganglionic fibres ext via lumbar splanchnic nerves to pelvis.
How many sacral sympathetic trunk ganglia are there and where do they exit?
- Postganglionic fibres exit via grey rami communicans to spinal nerves to lower limb AND sacral splanchnic nerves to pelvic organs.
What are the 6 major functions of the parasympathetic nervous system?
“Rest + Digest” : (1)Decrease pacemaker activity and contractile force of heart, (2) bronchoconstriction, (3) stimulates peristalsis and gastric secretions, (4) constrict pupils, (5) secretions of watery saliva and tears, (6)vasodilation of male erectile tissue and salivary glands
Which cranial nerves have parasympathetic functions?
3 (oculomotor)- edinger-westphal nucleus; 7 (facial) superior salivatory nucleus; 9 (glossopharyngeal) inferior salivatory nucleus; X (vagus) nucleus ambiguous, dorsal motor nucleus
What are sacral parasympathetic nerves responsible for?
Contraction of bladder wall (urination) and inhibition to bladder sphincter, Inhibition of rectal sphincter (enables defecation), Vasodilation in erectile tissues (causes erection, but sympathetic supply causes ejaculation)
What are the plexi of the enteric nervous system and what do they do?
Auerbach’s plexus (outside between muscles) regulates muscle contraction and meissner’s (on inside wall) plexus regulates glandular secretions
What makes the enteric nervous system autonomic?
Still functions if all central connections severed
What regulates the preganglionic and postganglionic neurons communication with effector organs? Name three levels.
Cerebral cortex to Hypothalamus to Autonomic centres in brainstem. All before pre/postganglionic neurons.
What causes vesicles to fuse with presynaptic cell membrane and release neurotransmitters into synaptic cleft?
Ca2+ influx from voltage-gated Ca2+ channels opening due to depolarised presynaptic cell.
What removes leftover neurotransmitter?
Glial cells
What anchors vesicles (above the active zone) to the cytoskeleton?
Synapsin
What is the process by which vesicles are released from the cytoskeleton?
Calcium binds to enzyme CaMKII (Calcium calmodulin activated kinase II) which phosphorylates synapsin. P-synapsin can no longer bind to cytoskeleton, vesicles dock to active zone.
What are the two phases a vesicle goes through before fusing with the presynaptic membrane?
docking and priming
What is the priming process vesicles docked to the membrane go through?
SNARE complex: vesicle v-SNARE proteins synaptobrevin and synaptotagmin (fuses w Ca2+) and target t-SNARE proteins syntaxin, SNARE-25 tied together
How is the vesicle membrane recovered?
Via endocytosis, buds off and filled with neurotransmitter by endosome.
Name two poisons that cleave SNARE complexes and their targets.
Both prevent transmitter release. (1) Botulinum toxin (BoTX) at neuromuscular transmission Acetylcholine, works at musclular junction and muscle loses all input so permanently relaxed; (2) Tetanus toxin (TeTX) interneurons at spinal cord, inhibits release of inhibitory neurotransmitters GABA and Glycine causing permanent muscle contraction
Name 4 areas of presyaptic terminal can be affected by disease besides BoTX and TeTX?
Congenital myasthmic syndromes affect vesicle recycling, latrotoxin triggers vesicle fusion, cognitive disorders impair transsynaptic signaling, LEMS attacks presynaptic Ca2+ channesl
What recycles amino acids, amines, and ACh into membrane to pack vesicles, and what drives them?
Membrane transporters driven by proton gradient (ATPase loads vesicles with H+) and electrochemical gradient (Na+/K+ pumps)
Which glial cells help recover neurotransmitters?
Astrocytes
What is the interaction between glial cells and the synapse?
The glial cell wraps around the synapse, and can take in neurotransmitters, which cause it to release neurotransmitters of its own that can inhibit or enhance synaptic activity.
Name 3 smaller neurotransmitters and where they are synthesized, where they’re stored, and what causes their release
Amino Acids, Monoamines, Acetylcholine. Synthesized locally in presynaptic terminal, stored in vesicles, released in response to global increase in Ca2+
Where are neuropeptides synthesized and stored and what prompts their release?
Synthesized in cell soma and transported to terminal, stored in secretory granules, released in response to global increase in Ca2+
When are neuropeptides used vs smaller neurotransmitter?
Neuropeptides in many frequent APs, smaller only if fewer or slower APs
What amino acid neurotransmitter is excitatory?
Glutamate
What amino acid neurotransmitter is inhibitory?
GABA (y-aminobutyric acid) in the brain and Glycine (Gly) in the spine
Why are there so many neurotransmitters?
They each have different functions and different neurons have different structures and functions that need to be performed.
How is glutamate synthesized? 2 Sources.
(1) from glucose in the krebs cycle, (2) from glutamine when converted by glutaminase
What happens to glutamate not taken up by a postsynaptic membrane?
taken up by glial cells, converted back to glutamine and transported back to nerve terminals where it is converted back to glutamate.
How is GABA synthesized?
From glutamate, catalyzed by glutamic acid decarboylase (GAD). Higher proportion of GABA is made de novo to refill vesicles rather than recycling
What transports GABA and Glycine to the presynaptic terminal?
GAT (vesicular GABA transporter)
How is GABA cleared from the synapse?
Reuptake on glia and neurons
What could too much glutamate lead to?
Hyper-excitbility, excitotoxicity, epilepsy
What could too much GABA cause?
sedation/coma
Describe cerebral ischemia on a molecular level.
metabolic events that retain electrochemical gradient are abolished, reversal of NA+/K+ gradient, transporters release glutamate from cells by reverse operation, excitotoxic cell death (Ca2+ -> enzymes -> digestion)
What is GHB gamma-hydroxybutyrate?
Date Rape Drug converted into GABA, increases available amount of GABA, too much leads to loss of consciousness and coma
What are the two groups of monoamines that form neurotransmitters?
Catecholamines: Dopamine, Epinephrine, and norepinephrine. Tyrosine main group. Indolamines: Serotonin. Tryptophan main group.
What are the steps of dopamine synthesis?
(1) Tyrosine main + tyrosine hydroxylase = L-dopa (L-dihydroxyphenylalanine). (2) L-dopa + Dopa Decarboxylase = Dopamine
What is L-dopa and what is its use?
Intermediate in making dopamine, used to treat Parkinson’s
What can you produce with dopamine?
Dopamine + Dopamino B-hydroxylase (DBH) = Norepinephrine. Norepinephtine + Phentolamine N-methyltransferase = epinephrine
Where is adrenaline produced and why does it have to be produced there?
In synaptic vesicles, because that is the only place DBH is located, which is needed to convert dopamine to norepinephrine.
