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Mixed revision > Revision: Theme 1 > Flashcards

Revision: Theme 1 Flashcards

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
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2
Q

Skulls sutures

A
  • coronal
  • saggital
  • lambdoid
  • Bregma
  • Lambda
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3
Q

Fontanelles

A
  • Anterior
  • Posterior
  • Mastoid
  • Sphenoidal (in front of mastoid!)
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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
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5
Q

Function of meninges

A
  • Protection
  • Support network for BV’s
  • Fluid filled cavity = Cushion + Nourishment
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6
Q

Dura mater innervation and blood supply

A

CN5 and 10
C 1,2,3
Sympathetic

MMA

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7
Q

Dura mater clinical application

A

Stretching = Headache
Damage to MMA = Extradural haemorrhage
Tentorial herniation = Space occupying lesion causes herniation of temporal lobe

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8
Q

Arachnoid mater and CSF

A
  • Subarachnoid space contains CSF
  • Provides buoyancy/protection
  • Arachnoid granulations affect CSF transfer to venous sinuses.
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9
Q

Pia

A

Delicate, vascular membrane = nourishment

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10
Q

Leptomeningitis

A
  • Infection/ inflammation of pia and arachnoid
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11
Q

Dural sinuses

A
  • Thick walled endothelium
  • No valves
  • No smooth muscle
  • Drain into int jug
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12
Q

Blood supply to brain

A
  • ICA + Vertebral arteries

- Terminal branches = anterior and middle cerebral

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13
Q

Main veins of brain

A
  • Anterior cerebral vein
  • Middle cerebral vein
  • Basal vein
  • Great cerebral vein

> To venous sinuses
Int jug

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14
Q

Neurulation

A
  • Neuroectoderm cells receive signal from notochord
  • Thicken to form neural plate
  • Fold to form neural tube
  • Day 20
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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
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16
Q

Development of brain: primary vesicles

A 
Prosencephalon = Forebrain
Mesencephalon = Midbrain
Rhombencephalon = Hindbrain
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17
Q

Development of the brain: Secondary vesicles

A 
Telencephalon = Cerebral hemispheres
Diencephalon = Thalamus, Hypothalamus
Mesencephalon = Midbrain
Metencephalon = Pons, Cerebellum
Myelencephalon = Medulla
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18
Q

Telencephalon

A
  • Cerebral hemispheres

- Components of limbic system and basal ganglia

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19
Q

Corpus Callosum

A

White matter tract linking cerebral hemispheres

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20
Q

Limbic system = Emotion and memory

A

Emotion + Memory

Main components:

  • Cingulate cortex
  • Fornix
  • Hypothalamus
  • Mamillary bodies
  • Hippocampus
  • Amydala
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21
Q

Fornix

A

White matter tract connecting hippocampus to maxillary bodies

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22
Q

Hippocampus

A

= Seahorse!

Sits in floor of lateral ventricle

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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.
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24
Q

Thalamus

A
  • Relays sensory info to cortex
  • Involved with voluntary movement
  • Personality
  • Consciousness
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25
Q

Hypothalamus

A
  • Homeostasis
  • Coordinates endocrine and ANS responses
  • Thermoregulation
  • Feeding
  • Drinking
  • Circadian Rhythms
  • Receives input from limbic system
  • Sits between optic chimes and maxillary bodies
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26
Q

Midbrain

A
  • 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
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27
Q

Brainstem

A 
Pons + Medulla ( Rhombencephalon) 
Contains:
- CN Nuclei
- Cardio and resp centres 
- Vomiting centre
- Nuclei for motor control and sleep
- White matter tracts
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28
Q

Pons ( means bridge!)

A
  • 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.
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29
Q

Medulla oblongata

A
  • 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
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30
Q

Cerebellum main functions

A
  • posture
  • coordinating and planning movements
  • eye movements
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31
Q

Cerebellum

A
  • Lobes = Anterior, flocculonodular, posterior
  • Arbor vitae = Tree of life
  • Connected to brainstem via cerebellar peduncles
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32
Q

Sensory ganglion

A

DRG

  • Big neurons
  • Central nuclei
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33
Q

Motor ganglion

A

Parasympathetic ganglion

  • Smaller
  • eccentric nuclei
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34
Q

How do glia differ from neurons?

A
  • No AP’s
  • do not form synapses
  • Can divide
  • More glia than neurons
  • Form myelin sheaths
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35
Q

oligodendrocyte (CNS)

A
  • Form myelin sheaths

- One cell myelinated multiple axons

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36
Q

Astrocyte

A
  • Supports neurons
  • Protects
  • Controls blood flow / BBB
  • Regulate exchange
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37
Q

Schwann cells (PNS)

A
  • One cell myelinated 1 axon
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38
Q

Satellite cells (PNS)

A
  • Regulate exchange of materials

- Support

39
Q

Electrical synapses

A
  • Faster
  • bidirectional
  • Coupled via gap junctions
  • smaller gap 3.5nm
  • No plasticity
  • No amplification
40
Q

Temporal summation

A

When input neuron is firing fast enough it can add together tiny signals to reach threshold

41
Q

Action potential

A
  • 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
Q

Coding intensity of neurons

A
  • Different neurons for different strength stimuli

- Firing frequency

43
Q

Action potentials vs graded potential

A

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
Q

Clinical uses of conduction velocities

A 
Investigate numbness, tingling, burning (paraesthesias)
Muscle weakness
peripheral neuropathy
carpal tunnel syndrome
spinal disc herniation
45
Q

Synaptic vesicle release and recycling

A
  • 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
Q

Tetanus

A
  • Inhibits glycine and Gaba release from inhibitory neutrons = disinhibition of ach = permanent muscle contraction.
47
Q

Vesicular transporters

A
  • Powered by proton gradient
  • ATPase pump loads vesicles with H+
  • H+ exchanged for 1 glutamate ( counter- transport mechanism)
48
Q

Plasma membrane transporters

A
  • powered by electrochemical gradient

- Glutamate co transported with 2 Na+

49
Q

Categories of neurotransmitters

A
  • 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
Q

Differential release of neurotransmitters

A

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
Q

Glutamate synthesis, release and reuptake

A
  • 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
Q

GABA synthesis, release, reuptake

A
  • 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
Q

Cerebral ischaemia = Excitotoxicity

A
  • 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
Q

Catecholamine synthesis

A

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
Q

Catecholamine storage, release reuptake

A
  • 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
Q

Drugs - catecholamine modulation

A

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
Q

Serotonin synthesis, storage, release, reuptake

A

Tryptophan > Tryptophan hydroxylase > 5-HTP > 5-HTP decarboxylase > 5-HT

  • stored in vesicles
  • Reuptake by SERT’S (serotonin transporters)
  • breakdown by MAO’s
58
Q

Serotonin drugs

A

SSRI’s - block repuptake e.g. fluoxetine
Fenfluramine - appetite suppression. Stimulates serotonin and blocks repuptake
- MDMA - NA and serotonin transporters to run backwards.

59
Q

Acetylecholine synthesis, storage, release, reuptake

A

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
Q

Neuropeptides

A
  • 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
Q

Endocannabinoids

A

decrease GABA release

small lipids

62
Q

Ionotroic receptors

A
  • fast transmission
  • ligand gated
  • glu, gaba, ach, atp, serotonin
  • Nicotinic achR leads to increased na and depolarisation and muscle contraction.
63
Q

Glutamate ionotropic receptors

A
  • NMDA, AMPA, Kainate

NMDA antagonist = APV
AMPA and Kainate antagonist = CNQX

64
Q

Non NMDA receptors = AMPA AND Kainate

A
  • Fast
  • K+ and na+ channels
  • repsonsible for early phase excitatory post synaptic potential
65
Q

NMDA receptor

A
  • 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
Q

NMDA dysregulation

A

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
Q

Other ionotropic receptors

A 
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
Q

Metabotropic receptors

A
  • G protein coupled

- slow transmission

69
Q

G-proteins

A
  • 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
Q

Second messanger: PIP2

A
  • phospholipase c
  • converts pip2 > ip3 and DAG
  • DAG > PKC
  • ip3 > releases calcium = released of calcium dependent enzymes.
71
Q

Metabotropic receptors

A
  • Metabotropic glutamate receptors
  • GABA(b)
  • Muscarinic ach receptor
  • dopamine receptors
  • NA and adrenergic
  • serotonin
  • neuropeptides
72
Q

Other receptors

A

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
Q

Generation of synchronous rhythms

A
  • 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
Q

CT vs MRI

A
  • 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
Q

PET vs fMRI

A
  • 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
Q

GABAergic system

A
  • widespread in brain
  • inhibitory interneurons
  • Too much GABA = sedation/coma
  • Too little GABA = seizures
  • Interneurons e.g. basket cells, axoaxonic cells
77
Q

GABA(a)

A
  • Ionotropic
  • fast
  • mainly GABAergic interneurons
  • Cl- channel gated by binding of 2 ligands = hyper polarisation
  • 2 a and 3 b subunits
78
Q

GABA(b)

A
  • metabotropic
  • slow
  • indirectly couple to K+ (opens) or ca2+ (closes) channels
  • pre and post synaptic
  • Balcofen = agonist ( muscle relaxant e.g. huntingtons)
79
Q

GABA(a) drugs

A
  • 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
Q

The dopaminergic system

A
  • 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
Q

Dopamine receptors

A
  • 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
Q

Nigrostriatal system

A

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
Q

Mesolimbic system

A

Cell bodies in VTA project to limbic, Nacc
Role in reinforcement (drugs of abuse)

Dysfunction

  • Addiction = cocaine, amphetamine increase dopamine (reward)
84
Q

Mesocortical pathway

A

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
Q

Serotonergic system

A
  • 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
Q

Serotonergic system functions

A
  • Mood
  • Sleep
  • Pain
  • emotion
  • appetite
87
Q

Serotonergic drugs

A

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
Q

Noadrenergic system

A
  • Projections from Locus coeruleus throughout brain.
  • arousal and attention
  • Metabotropic receptors e.g alpha adrenergic a1 and a2 and beta adrenergic
89
Q

Adrenergic system

A
  • LTA projecting to thalamus and hypothalamus

- a adrenergic and b adrenergic receptors

90
Q

Cholinergic system

A
  • 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
Q

Cholinergic system disorders

A
  • 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
Q

Cholinergic system: Drugs

A
  • Cholinesterase inhibitors = prolonged action of each at synapse. Alzeihmers (Physostigmine), MG (Neostigmine)
93
Q

Ach receptors

A 
Metabotropic = Muscarinic. Muscarine (agonist), Atropine (antagonist)
Ionotropic = Nicotinic. Nicotine (agonist), Curare (antagonist).
94
Q

Histaminergic system

A
  • Arousal
  • allergic response
  • Reactivity of vestibular system
  • Influence blood brain flow
  • 3 x g protein coupled receptors

Mixed revision (3 decks)

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