Revision: Theme 1 Flashcards
(94 cards)
1
Q
Criteria that define a neurotransmitter
A
- Synthesized in neuron
- Stored in presynaptic terminal and released in amounts that exert a defined effect on post synaptic neutron
- When administered as a drug, mimics action of endogenous neurotransmitter.
- Specific mechanism exists for removal from synaptic cleft
2
Q
Skulls sutures
A
- coronal
- saggital
- lambdoid
- Bregma
- Lambda
3
Q
Fontanelles
A
- Anterior
- Posterior
- Mastoid
- Sphenoidal (in front of mastoid!)
4
Q
Foramina
A
Cribiform = Olfactory CN1 Optic = Optic nerve CN2 Superior orbital fissure = CN3,4,6 + V1 (ophthalmic) Foramen rotundum = v2 (maxillary) Foramen ovale = v3 Foramen spinosum = MMA Foramen lacerum = ICA Internal acoustic meatus = CN7,8 Jugular foramen = CN9, 10, 11 + IJV Hypoglossal canal = CN12 Carotid canal = ICA Stylomastoid foramen = CN7 Foramen magnum = SC, medulla, vertebral arteries, CN11
5
Q
Function of meninges
A
- Protection
- Support network for BV’s
- Fluid filled cavity = Cushion + Nourishment
6
Q
Dura mater innervation and blood supply
A
CN5 and 10
C 1,2,3
Sympathetic
MMA
7
Q
Dura mater clinical application
A
Stretching = Headache
Damage to MMA = Extradural haemorrhage
Tentorial herniation = Space occupying lesion causes herniation of temporal lobe
8
Q
Arachnoid mater and CSF
A
- Subarachnoid space contains CSF
- Provides buoyancy/protection
- Arachnoid granulations affect CSF transfer to venous sinuses.
9
Q
Pia
A
Delicate, vascular membrane = nourishment
10
Q
Leptomeningitis
A
- Infection/ inflammation of pia and arachnoid
11
Q
Dural sinuses
A
- Thick walled endothelium
- No valves
- No smooth muscle
- Drain into int jug
12
Q
Blood supply to brain
A
- ICA + Vertebral arteries
- Terminal branches = anterior and middle cerebral
13
Q
Main veins of brain
A
- Anterior cerebral vein
- Middle cerebral vein
- Basal vein
- Great cerebral vein
> To venous sinuses
Int jug
14
Q
Neurulation
A
- Neuroectoderm cells receive signal from notochord
- Thicken to form neural plate
- Fold to form neural tube
- Day 20
15
Q
Development of nervous system
A
- Lumen > Ventricles + central canal
- Ependymal cells > Line ventricles
- Mantle layer > Brain parenchyma
- Neural crest cells > Neurons and glia (sensory + ANS), cells of adrenal gland, Epidermis + Skeletal/ connective tissue of head.
- Ectoderm
- Day 24
16
Q
Development of brain: primary vesicles
A
Prosencephalon = Forebrain Mesencephalon = Midbrain Rhombencephalon = Hindbrain
17
Q
Development of the brain: Secondary vesicles
A
Telencephalon = Cerebral hemispheres Diencephalon = Thalamus, Hypothalamus Mesencephalon = Midbrain Metencephalon = Pons, Cerebellum Myelencephalon = Medulla
18
Q
Telencephalon
A
- Cerebral hemispheres
- Components of limbic system and basal ganglia
19
Q
Corpus Callosum
A
White matter tract linking cerebral hemispheres
20
Q
Limbic system = Emotion and memory
A
Emotion + Memory
Main components:
- Cingulate cortex
- Fornix
- Hypothalamus
- Mamillary bodies
- Hippocampus
- Amydala
21
Q
Fornix
A
White matter tract connecting hippocampus to maxillary bodies
22
Q
Hippocampus
A
= Seahorse!
Sits in floor of lateral ventricle
23
Q
Basal ganglia
A
- Corpus striatum = Lentiform + caudate nucleus
- Lentiform = Putamen + Globus pallidus
- Caudate nucleus sits in wall of lateral ventricle.
- Lentiform sits lateral to caudate nucleus.
24
Q
Thalamus
A
- Relays sensory info to cortex
- Involved with voluntary movement
- Personality
- Consciousness
25
Hypothalamus
- Homeostasis
- Coordinates endocrine and ANS responses
- Thermoregulation
- Feeding
- Drinking
- Circadian Rhythms
- Receives input from limbic system
- Sits between optic chimes and maxillary bodies
26
Midbrain
- Mesencephalon
- Cerebral peduncles are white matter tracts that connect pons to diencephalon
- Superior colliculi = Vision
- Inferior colliculi = auditory
- Red nucleus = Motor coordination relay between cortex and cerebellum
- Substantia nigra = Dopaminergic neurons, part of basal ganglia
27
Brainstem
```
Pons + Medulla ( Rhombencephalon)
Contains:
- CN Nuclei
- Cardio and resp centres
- Vomiting centre
- Nuclei for motor control and sleep
- White matter tracts
```
28
Pons ( means bridge!)
- Relays info to cerebellum
- 90% of axons descending through midbrain synapse in pons
- Middle cerebellar peduncle connects brainstem to cerebellum
- Contains reticular information = Nuclei involved in sleep and motor control.
29
Medulla oblongata
- cardio and resp centres
- Pyramid = corticospinal tract - Main voluntary motor pathway
- Olive = Olivary nuceli - Motor relay to cerebellum
- Cuneate tubercle (lat) = Ascending tract
- Gracile tubercle (medial) Ascending tract
30
Cerebellum main functions
- posture
- coordinating and planning movements
- eye movements
31
Cerebellum
- Lobes = Anterior, flocculonodular, posterior
- Arbor vitae = Tree of life
- Connected to brainstem via cerebellar peduncles
32
Sensory ganglion
DRG
- Big neurons
- Central nuclei
33
Motor ganglion
Parasympathetic ganglion
- Smaller
- eccentric nuclei
34
How do glia differ from neurons?
- No AP's
- do not form synapses
- Can divide
- More glia than neurons
- Form myelin sheaths
35
oligodendrocyte (CNS)
- Form myelin sheaths
| - One cell myelinated multiple axons
36
Astrocyte
- Supports neurons
- Protects
- Controls blood flow / BBB
- Regulate exchange
37
Schwann cells (PNS)
- One cell myelinated 1 axon
38
Satellite cells (PNS)
- Regulate exchange of materials
| - Support
39
Electrical synapses
- Faster
- bidirectional
- Coupled via gap junctions
- smaller gap 3.5nm
- No plasticity
- No amplification
40
Temporal summation
When input neuron is firing fast enough it can add together tiny signals to reach threshold
41
Action potential
- Resting - Inward rectifier K+ channels open. K+ flowing out. Membrane = -70mV
- Stimulus causes membrane to depolarise
- Na+ channels open, Na + flows in = more depolarisation. (positive feedback)
- Threshold (-55mV) reached = Action potential
- positive feedback continues (+40)
Repolarisation
- Due to passage of time, Na + channels close
- Delayed rectifier K+ channels open ( more negative)
After-hyperpolarisation
- Refractory period - Neuron incapable of generating AP
- More negative than rest
- Inward rectifier K+ channels open again
- decreased na+ permeability
= Resting membrane potential
42
Coding intensity of neurons
- Different neurons for different strength stimuli
| - Firing frequency
43
Action potentials vs graded potential
AP'S:
- Sterotyped signal
- All or nothing
- Spike
- short duration
- neurons, skeletal and cardiomyocytes
- require time to start due to conformational changes
Graded potentials:
- Electrically localised
- Attenuate
- longer duration
- Variable
- Flatter
- Conducted almost instantly
44
Clinical uses of conduction velocities
```
Investigate numbness, tingling, burning (paraesthesias)
Muscle weakness
peripheral neuropathy
carpal tunnel syndrome
spinal disc herniation
```
45
Synaptic vesicle release and recycling
- Vesicles anchored to cytoskeleton via synapsin
- AP causes calcium channels to open
- Calcium activates CamKII
- CamKII phosphorylates synapsin. Phosphorylated synapse can no longer bind to cytoskeleton
- Vesicles dock to active zone via snare complexes
- Calcium binds to synaptotagmin
- Calcium bound synatotagmin catalyses membrane fusion by binding to SNAREs and plasma membrane
- Exocytosis
- Vesicle membrane recovered via endocytosis.
46
Tetanus
- Inhibits glycine and Gaba release from inhibitory neutrons = disinhibition of ach = permanent muscle contraction.
47
Vesicular transporters
- Powered by proton gradient
- ATPase pump loads vesicles with H+
- H+ exchanged for 1 glutamate ( counter- transport mechanism)
48
Plasma membrane transporters
- powered by electrochemical gradient
| - Glutamate co transported with 2 Na+
49
Categories of neurotransmitters
- Amino acids
- Monoamines
- Ach
* Synthesised locally in presynaptic terminal, stored in synaptic vesicles, released in response to local increase in calcium
- Neuropeptides
* synthesised in soma, stored in secretory granules, released in response to global increase in calcium.
* Slow
50
Differential release of neurotransmitters
Low freq stimulation = Localised release of calcium. Release of small molecule neurotransmitter near synaptic terminal.
High freq = Release of both types of neurotransmitters due to global increase in calcium.
51
Glutamate synthesis, release and reuptake
- Glutamate synthesized from glucose and glutamine
- Glutamine > Glutaminase > Glutamate
- loaded and stored in vesicles by vesicular glutamate transporters
- Reuptake by EAATS (Excitatory amino acid transporters) on presynaptic cell and glia
- Glia convert glutamate to glutamine
- Glutamine transported back to nerve terminals where it is converted back to glutamate.
52
GABA synthesis, release, reuptake
- GABA synthesised from glutamate (catalysed by glutamate decarboxylase)
- Loaded and stored onto vesicles by by vesicular GABA transporters
- Reuptake by transporters on glia and neurons
- High proportion of GABA made de novo rather than recycling
53
Cerebral ischaemia = Excitotoxicity
- Metabolic events that maintain electrochemical gradient abolished
- Reversal of na+/k+ gradient
- Transporters release glutamate by reverse operation
- Too much calcium > enzymes > digestion leading to excitotoxic cell death.
54
Catecholamine synthesis
Tyrosine> tyrosine hydroxylase > dopa > dopa decarboxylase > dopamine
Dopamine > dopamine beta hydroxylase > NA > phentolamine N- methyltransferase > adrenaline
DBH only present in vesicles, NA is only transmitter synthesised in vesicles.
55
Catecholamine storage, release reuptake
- vesicular monoamine transporters (also use proton gradient)
- released via ca2+ dependent exocytosis
- Reuptake by Dopamine transporters and monoamine transporters
In cytoplasm
- reloaded back in vesicles
- degraded by MAO
- or inactivated by COMT
56
Drugs - catecholamine modulation
Amphetamines = Reverse transport pumps out transmitter and blocks repute (dopamine and NA)
Cocaine and ritalin = Block dopamine repute
Selegiline = MAO inhibitor = prevents breakdown of dopamine
Entacapone = COMT inhibitor
57
Serotonin synthesis, storage, release, reuptake
Tryptophan > Tryptophan hydroxylase > 5-HTP > 5-HTP decarboxylase > 5-HT
- stored in vesicles
- Reuptake by SERT'S (serotonin transporters)
- breakdown by MAO's
58
Serotonin drugs
SSRI's - block repuptake e.g. fluoxetine
Fenfluramine - appetite suppression. Stimulates serotonin and blocks repuptake
- MDMA - NA and serotonin transporters to run backwards.
59
Acetylecholine synthesis, storage, release, reuptake
acetyl coa + choline > choline acetyltransferase > acetylcholine
packaged into vesicles by vesicular acetylcholine transporters
degraded in cleft by acetylcholinesterases
- choline transported back to presynaptic to be converted back to ach.
- amount of choline is rate limiting step
Drugs = acetylcholinesterase e.g neostigmine (MG)
60
Neuropeptides
- Vary in methods of synthesis and release
- slow transmission
- endorphins, substance p, neuopeptide y, opiods, vasopressin
- Follow secretory pathway
- membrane recycled but not refilled
- degraded by proteases
- slower but signals may be maintained for longer
61
Endocannabinoids
decrease GABA release
| small lipids
62
Ionotroic receptors
- fast transmission
- ligand gated
- glu, gaba, ach, atp, serotonin
- Nicotinic achR leads to increased na and depolarisation and muscle contraction.
63
Glutamate ionotropic receptors
- NMDA, AMPA, Kainate
NMDA antagonist = APV
AMPA and Kainate antagonist = CNQX
64
Non NMDA receptors = AMPA AND Kainate
- Fast
- K+ and na+ channels
- repsonsible for early phase excitatory post synaptic potential
65
NMDA receptor
- Slow
- Permeable to na`+, k+ and ca 2+
- require glycine cofactor to open channel
- also gated by membrane voltage
- mg2+ plugs pore until cell becomes depolarised = activity dependant synaptic modification
- responsible for late phase excitatory post synaptic potential
- activated only in an already depolarised membrane in presence of glutamate
*activity of calcium triggers other cellular events that lead to neuroplasticity and LTM.
66
NMDA dysregulation
Schizophrenia?
- PCP block NMDA receptors (glutamate antagonist)
- produces schizophrenia sympons (hallucinations)
Glutamate excitotoxicity
- excess calcium activates enzymes that lead to cell damage e.g. after stroke, cardiac arrest
67
Other ionotropic receptors
```
Glutamate = excitatory
Gaba(a) = inhibitory (brain)
Glycine = Inhibitory (brainstem and spinal cord)
Nicotine = excitatory at NMJ and excitatory/modulatory in CNS
Serotonin = Excitatory or modulatory
ATP = Excitatory
```
68
Metabotropic receptors
- G protein coupled
| - slow transmission
69
G-proteins
- Binding of neurotransmitter
- GDP > GTP
- Heteromer splits into Ga and Gbeta gamma
- stimulate activity of effector proteins
- Alpha subunit had intrinsic GTP-GDP enzyme activity allowing signal to be transient. GTP breakdown switches off activity
- Hetromer recomplexes and awaits binding of another neurotransmitter
Gs - stimulates adenylyl cyclase
Gq - stimulates phospolipase c
Gi - inhibits adenylyl cyclase
Beta-gamma complex:
- Activate K+ channels directly "shortcut pathway"
e. g muscarinic ach in heart and GABA(b)
- method of amplifying signals
70
Second messanger: PIP2
- phospholipase c
- converts pip2 > ip3 and DAG
- DAG > PKC
- ip3 > releases calcium = released of calcium dependent enzymes.
71
Metabotropic receptors
- Metabotropic glutamate receptors
- GABA(b)
- Muscarinic ach receptor
- dopamine receptors
- NA and adrenergic
- serotonin
- neuropeptides
72
Other receptors
enzyme-linked:
e.g. receptor tyrosine kinases activated by neurotrophic binding (NGF) > autophosphorylate > phosphorylate intracellular regulatory subunits > signalling cascades
Intracellular receptors:
Membrane permeant molecules activate them
73
Generation of synchronous rhythms
- thalamic pacemaker cells
- have voltage gated ion channels
- allow each cell to generate rhythmic, self sustaining discharge patterns in absence of external stimulus
- Rhythmic activity becomes synchronised with other thalamic cells.
74
CT vs MRI
- CT e.g diagnose tumours, haemorrhage
- MRI safe as no radiation
- Patients can be scanned many times
- MRI has better spatial resolution
MRI can distinguish white and grey matter
- MRI can be adapted = fMRI
75
PET vs fMRI
- PET measures blood flow
- fMRI measures conc of o2
- PET involves radioactivity
- fMRI no radiation so patients can be scanned many times
- PET temporal = 30 spatial = 10
- fMRI = temporal = 1-4 spatial = 1
BOLD = blood oxygen level dependant contrast
Haemodynamic response function = change in BOLD over time
76
GABAergic system
- widespread in brain
- inhibitory interneurons
- Too much GABA = sedation/coma
- Too little GABA = seizures
- Interneurons e.g. basket cells, axoaxonic cells
77
GABA(a)
- Ionotropic
- fast
- mainly GABAergic interneurons
- Cl- channel gated by binding of 2 ligands = hyper polarisation
- 2 a and 3 b subunits
78
GABA(b)
- metabotropic
- slow
- indirectly couple to K+ (opens) or ca2+ (closes) channels
- pre and post synaptic
- Balcofen = agonist ( muscle relaxant e.g. huntingtons)
79
GABA(a) drugs
- muscimol = direct agonist
- Bicuculline = direct antagonist
- Benzos = indirect agonists that increase receptor affinity for GABA. Binds alpha subunit.
- Barbituates = indirect agonist. Increase duration of channel opening
- Alcohol = indirect agonist
80
The dopaminergic system
- substantia nigra and ventral tegmental area (midbrain) cell bodies project into forebrain
- Nigrostriatal sytem = motor control. Cell bodies in SN project to striatum. Basal ganglia = involved in voluntary movement
- mesolimbic
- mesocortical (behaviour)
81
Dopamine receptors
- Metabotropic
- dopamine can be excitatory and inhibitory
- D1 like (1&5) = excitatory = gs as stimulate adenylyl cyclase
- D2 (2,3,4) = Inhibitory = Inhibit adenylyl cyclase, open K+ channels, close ca2+
82
Nigrostriatal system
Motor control. Cell bodies in SN project to striatum. Basal ganglia = involved in voluntary movement
Dysfunction = PD destruction of SN cells
Huntingtons = Destruction of dopamine target cells in striatum
83
Mesolimbic system
Cell bodies in VTA project to limbic, Nacc
Role in reinforcement (drugs of abuse)
Dysfunction
- Addiction = cocaine, amphetamine increase dopamine (reward)
84
Mesocortical pathway
VTA > prefrontal cortex (working memory, planning)
Dysfunction = Schizophrenia
Typical antipsychotics e.g. Haloperidol, chlorpromazine
= Dopamine receptor antagonists. eps
Atypical e.g. Clozapine = anatagonist of D4. Less EPS
85
Serotonergic system
- Raphe nuclei in reticular formation with diffuse projections
- Descending projections to cerebellum and SC = Pain
- Ascending projections reticular activating system (with LC)
- Dorsal and medial raphe project throughout cerebral cortex
- Tonically active during wakefulness. quiet during sleep
86
Serotonergic system functions
- Mood
- Sleep
- Pain
- emotion
- appetite
87
Serotonergic drugs
SSRI'S = Serotonin reuptake inhibitors. Treatment for depression and anxiety.
MDMA = Causes serotonin (and NA) to transporters to run backwards. Increased release or serotonin and decreased reuptake.
LSD = Potent serotonin receptor agonist. = Altered perceptions, hallucinogenic, dream-like state
88
Noadrenergic system
- Projections from Locus coeruleus throughout brain.
- arousal and attention
- Metabotropic receptors e.g alpha adrenergic a1 and a2 and beta adrenergic
89
Adrenergic system
- LTA projecting to thalamus and hypothalamus
| - a adrenergic and b adrenergic receptors
90
Cholinergic system
- In periphery = ach in NMJ and ANS
- In brain = basal forebrain complex - cholinergic innervation of hippocampus and neocortex
- Brainstem complex = Diencephalon and telencephalon. Control excitability of sensory relay neurons. Provide cholinergic link between basal forebrain and brainstem.
91
Cholinergic system disorders
- Myasthenia graves (peripheral) - autoimmune destruction of cholinergic receptors = muscle weakness and loss of activity
- Alzeihmers = loss of cholinergic neurons in basal ganglia.
- Nicotine addiction -
- Epilepsy - autosomal dominant frontal lobe epilepsy. Mutations in nicotinic receptors.
92
Cholinergic system: Drugs
- Cholinesterase inhibitors = prolonged action of each at synapse. Alzeihmers (Physostigmine), MG (Neostigmine)
93
Ach receptors
```
Metabotropic = Muscarinic. Muscarine (agonist), Atropine (antagonist)
Ionotropic = Nicotinic. Nicotine (agonist), Curare (antagonist).
```
94
Histaminergic system
- Arousal
- allergic response
- Reactivity of vestibular system
- Influence blood brain flow
- 3 x g protein coupled receptors
