Basic Neuroscience Flashcards
1
Q
In H&E, what does Haemotoxylin stain and what colour?
A
Nucleic Acids (nucleolus) blue
2
Q
In H&E what does Eosin stain and what colour?
A
Proteins red
3
Q
In a chemical synapse, what does depolarisation of synaptic terminal cause?
A
Opening VGCCs, triggering NT release
4
Q
How do ions flow between electrical synapses?
A
through connexins directly opposite to each other
5
Q
Which kind of synapses are often concentrated on dendritic spines?
A
Excitatory- often glutamate
6
Q
Which diseases have been linked to reduced dendritic spine density?
A
AD and SZ
7
Q
What are Betz cells?
A
Upper motor neurons found in motor cortex, large, excitatory (glut), long projections, pyramidal cells
8
Q
What disease are Betz cells vulnerable to
A
MND
9
Q
What are medium spiny neurons?
A
small striatal inhibitory (GABA) interneurons
10
Q
what disease are medium spiny neurons vulnerable to?
A
HD
11
Q
2 functions of oligodendrocytes
A
myelinating and metabolic support
12
Q
Can one oligodendrocyte sheath several neurons?
A
Yes
13
Q
What electrochemically allows tight binding between myelin and neurons
A
positively charged MBP proteins - bind to negative neurons
14
Q
What do microglia look like in resting state?
A
highly ramified with surveying motile processes
15
Q
what do microglia look like upon activation
A
small, dense, amoeboid
16
Q
What are the 2 types of microglia?
A
M1 and M2
17
Q
What is M1 microglia?
A
Pro-inflammatory ‘bad’ cytokine production
18
Q
What is M2 microglia?
A
Neuroprotective ‘good’ cytokine production
19
Q
How are microglia involved in synaptic plasticity
A
phagocytic dendritic pruning
20
Q
Which are the most abundant glial cell?
A
Astrocytes
21
Q
what’s a key marker used to detect astrocytes?
A
GFAP (glial fibrillary acidic protein)
22
Q
how do astrocytes contribute to BBB
A
their end-feet
23
Q
Are A1 astrocytes proinflammatory or neuroprotective?
A
proinflammatory
24
Q
are A2 astrocytes proinflammatory or neuroprotective?
A
neuroprotective
25
Name 3 specialised Glia
Radial Glia, Bergmann Glia, Muller Cells
26
Define Nuclei in CNS
group of cell bodies
27
Define tracts in CNS
group of axons
28
Define Ganglia in PNS
group of cell odies and supporting cells
29
Define Nerves in PNS
axon bundles
30
name 4 contributors to the BBB
endothelial tight cell junctions, basement membrane with few fenestrations, astrocyte end feet and pericytes
31
What lack normal BBB?
circumventricular organs
32
Name 2 circumventricular organs:
Posterior Pituitary Area Postrema, Pineal Body
33
Name 2 routes for CSF reabsorption
Arachnoid granulations, meningeal lymphatics, perineural spaces
34
Describe ependymal cells
Epithelial-like, lines ventricles and spinal cord, CSF production/flow, ciliated
35
Describe Choroid Plexus
frond-like projections in ventricles, modified ependymal cells, highly vascularised and clustered, CSF production, CSF-blood barrier
36
Which ion gradient is the primary determinant of resting membrane potential?
K+
37
Which other 2 ions (other than K+) have an effect on resting membrane potential
Na+ and Cl-
38
What causes depolarisation simply?
influx of Na+
39
What causes repolarisation simply?
closure of Na+ channels and opening of K+ VG channels
40
What causes hyperpolarisation simply?
K+ VG channels staying open after resting potential reached
41
Which ion channel does TTX block?
Na+
42
Which ion channels does TEA block?
K+
43
enough EPSP causes
generation of AP
44
what's the most common cause of an EPSP generating AP
influx of Na+ ions from positive NT glutamate
45
Does a larger stimulus produce a larger AP?
no
46
Does a larger stimulus produce more APs?
Yes
47
can a second stimulus in the absolute refractory period trigger another AP?
No
48
can a second stimulus in the relative refractory period trigger another AP?
yes, however, it may need to be larger as the cell is in a hyperpolarised state
49
What is the advantage of refractory period?
it favours unidirectional propogration
50
What do uniporters do?
one substance in one direction
51
what do symporters do?
2 substances, 1 direction
52
what do antiporters to
2 substances in opposite directions
53
give 2 examples of uniporters
Na+, K+. Cl-, Ca2+ channels
54
give 2 examples of symporters
Na/Cl-/K+ cotransporter
K+/Cl- cotransporter
Na+/Neurotransmitter co-transporter e.g. DAT
55
Give 2 types of antiporters
ATPase pumps and ion exchangers
56
Which active process contributes towards maintaining electrochemical gradient in neuron
Na+/K+ ATPase
57
what ratio in/out for Na+/K+ ATPase
3 Na+ out and 2 K+ in
58
describe the structure of Na+/K+ ATPase
10 alpha TM helices, mainly cytoplasmic
Single beta helix- mainly extracellular
N, P and A domains
59
What 2 toxins inhibit Na+/K+ ATPase?
Digoxin an Ouabain
60
What are the 2 types of Ca2+ ATPases?
PMCA and SERCA
61
what are Ca2+ ATPases structurally similar to?
Na+/K+ ATPases
62
what 3 important structures do VGSC contain?
voltage sensor (charged helix)
selectivity filter (pore)
gating mechanisms (on-off)
63
what are the 2 main types of drugs which target Na+ VGSCs?
Antiepileptics e.g. lamotrigine and Anaesthetics e.g. lidocaine
64
What's the mechanism of the opening and closing of VGSCs?
charged helix voltage sensor detects membrane depolarisation and changes shape to allow Na+ influx, it is rapidly inactivated by channel-inactivating segment (plug) during hyperpolarisation
65
Which ion channel is a key target of toxins?
VGSCs
66
Name 2 disorders that mutations of VGSC genes are linked to
epilepsy, migraine, ASD, ataxia, pain insensitivity, extreme pain disorder
67
What are VG potassium channels structurally similar to?
VGSCs
68
Describe the structure of VGPCs
4 alpha subunits with 6 TM helices and regulatory Beta subunits
69
Name 1 disorder linked with VGPC gene mutations
epilepsy and ataxia
70
name 2 disorders linked to Calcium channel gene mutations
ataxia, migraine, childhood absence epilepsy
71
What aspects of an ion channel can channelopathies effect? name 2
channel assembly/ function, permeability, gating, inactivation
72
what's a dominant negative mutation
where a mutation in one subunit impacts all other subunits
73
Name 3 different Ionotropic receptors/ ligand-gated ion channels
NMDA/AMPA/Kainate
nAChR
5-HT
GlyR
GABAb
74
What is an ionotropic receptor
where the receptor is an ion channel itself
75
what are transient receptor potential (TRP) channels?
cation channels, gated by a number of factors, linked to pain, migraine and itch, found in PNS and CNS
76
Name 2 differences between electrical and chemical synaptic transmission
fewer electrical synapses
faster transmission of electrical
narrower synapses of electrical
electrical less tightly regulated
77
Which aspect of electrical transmission has genetic disease relevance?
Conexins
78
What disorder is linked to GJB1 connexin gene mutation?
Charcot-Marie Tooth neuropathy
79
What disorder is linked to GJC2 connexin gene mutation
Lewy Dystrophy or spastic Paraplegia
80
Name the 3 criteria which define NTs
- present in presynaptic neuron
- released in response to presynaptic neuron depolarisation with Ca2+ dependant release
- Specific receptors present on postsynaptic cell
81
What are the 2 main classes of NT?
Small Molecule and Peptide NTs
82
What are the 2 types of neurotransmitter production/transport?
Slow-Axonal and Fast-Axonal
83
What kind of NTs travel by slow-axonal transport?
small
84
describe fast-axonal transport of NTs
they travel in vesicles down microtubule tracks
85
describe the 2 types of vesicles and what they hold
Small clear, hold small NTs suchas Gly, Glu, GABA ACh and ATP
Dense-core, hold serotonin, histamine, catecholamines, neuropeptides
86
What coats synaptic vesicles
proteins
87
What are SNAPs
Synaptic Associated Proteins
88
How does exocytosis occur in NT vesicles, with reference to SNAREs
SNAP receptors on vesicles interact with SNAREs and other proteins on pre-synaptic terminal causing pore to open. Afterwards SNARE complexes disassemble and vesicles are recycled
89
Which 2 toxins target SNARE proteins?
botulinum (botox) and tetanus (these toxins are proteases which cleave SNAREs)
90
What are the 3 main types of synaptic membrane vesicle recyling?
Clathrin mediated endocytosis
ultrafast endocytosis
Kiss-and-run endocytosis
91
How does Clathrin-mediated endocytosis occur?
Pits form in synaptic terminal after exocytosis and clathrin forms a network over budding membranes, which narrow and bud off
92
What is ultrafast endocytosis?
Where larger membrane sacs are formed at distal sites, away from vesicle release
93
What is a tri-partite synapse?
One where pre- and post-synaptic terminals and glial cells (astrocytes) reuptake ions/NTs
94
As well as components of tri-partite synapse, what else removes NTs from synapse?
enzymes- break them down
95
What are the 2 key types of NT receptor?
ionotropic and metabotropic
96
which type of NT receptor tends to act faster with shorter term effects?
Ionotropic
97
What structure are most metabotropic receptors
GPCRs
98
How many subunits tend to make up a GPCR?
3
99
What is summation
The sum of inhibitory and excitatory inputs- which summate in whether or not an AP is produced
100
Is glutamate a small or large NT?
Small
101
Are GABA and Glycine big or small NTs
small
102
Is Glutamate charged?
yes
103
are GABA and glycine charged?
No
104
What is GABAs main role?
Main brain inhibitory NT
105
How is GABA sythesised?
from glutamate by glutamic acid decarboxylase (GAD)
106
What loads GABA into synaptic vesicles?
vesicular inhibitory amino acid transporter (VIAAT)
107
What clears GABA from the synapse?
GABA transporter (GAT)
(an Na+ dependent co-transporter)
108
What are the 2 main types of GABA receptor?
GABAa and GABAb
109
Describe GABAa
ionotropic
chloride channel
2 alpha, 2 beta, 1 gamma subunit
110
Describe GABAb
metabotropic
hyperpolarise by driving K+ out of cell and inhibiting Ca2+ influx
G-protein signalling
111
What do agonists of GABAa generally do
Sedate/ CNS depressants
112
Name 3 classes of GABAa agonists
anxiolytics, anti-convulsants, anaesthetics, barbiturates, benzos
113
What do Barbiturates do at the GABAa receptor?
activate it
114
What do Benzos do at the GABAa receptor?
enhance
115
What do antagonists of GABAa receptors do?
used for Benzo ODs and epilepsy models
116
What are GABAb agonists used for?
spasticity (MND and MS)
117
what are GABA reuptake inhibitors used for?
focal seizures
118
What are GABA analogues (agonists) used for?
seizures/ neuropathic pain e.g. gabapentin
119
Is GABA inhibitory or excitatory in early brain development?
excitatory
120
Describe GABA's excitatory function in early brain development
immature brain has high levels of NKCC1 (sodium potassium chloride channel 1) where GABA causes efflux of Cl- -- depolarising
121
Why is it important for GABA to be excitatory in early development?
brain is growing and growth and connections need to be stimulated
122
What's different about GABA in mature brain?
higher KCC2 channels and low Cl-, where Cl- influx due to GABA causes inhibition
123
What is Glycine's overall role?
Main inhibitory NT in spinal cord and brainstem
124
What loads Glycine into vesicles?
VIAAT
125
What clears Glycine from synapses?
GlyT (Glycine transporter)
126
What causes Hyperplexia?
Mutations in GlyT
127
What is hyperlexia?
exaggerated startle
128
Why does an increase in Glycine in Hyperlexia cause excitatory symptoms?
Desensitisation of post-synaptic membrane
129
What is Hyperlexia managed with?
Clonazepam (Benzo)
130
What kind of receptor are Glycine receptors?
Ionotropic Chloride Channels
131
What's the structure of Glycine receptors?
5 subunits
3 alpha and 2 beta each with 4 TM domains clustered by gephryn
132
What kind of NT class is ATP?
Purine
133
Are Purines Excitatory of Inhibitory?
Excitatory
134
Where is ATP found as an NT?
CNS and PNS
135
Is adenosine a NT?
No it's a neuromodulator
136
What class of receptor responds to purines?
Both ionotropic and metabotropic
137
What, structurally makes an NT an Amine?
Ring structure
138
give examples of biogenic amine NTs
Catecholamines (Dopamine, Noradrenaline, Adrenaline)
Histamine
Serotonin
139
Describe the biosynthesis of Catecholamines
L-tyrosine--> L-Dopa --> Dopamine --> Noradrenaline --> Adrenaline
140
What loads catecholamine NTs in vesicles?
monoamine transporter (VMAT)
141
What catabolises catecholamines? (2)
MAO (monoamine oxidase) and COMT (catech-O-methyltransferase)
142
What are the 3 pathways of Dopaminergic neurons?
nigrostriatal
mesolimbic
mesocortical
143
Describe the nigrostriatal dopaminergic pathway
From SN to Striatum
involved in movement
144
Describe the mesolimbic dopaminergic pathway
from midbrain ventral tegmentum to limbic system
involved in reward
145
Describe the mesocortical dopaminergic pathway
from midbrain ventral tegmentum to cortex
involved in cognition, emotion
(affected in SZ)
146
What removes dopamine from synapses?
DAT (dopamine transporter) (Na+ dependent co-transporter)
147
What drugs target DAT?
Cocaine and Amphetamines
148
What disease are MAO and COMT inhibitors used in?
PD
149
What class of receptors are dopamine receptors?
Metabotropic
150
What are the 2 classes of dopaminergic receptors?
D1-like Gs
D2-like Gi
151
What's the differences between D1-like Gs and D2-like Gi receptors?
D1- stimulatory- increase cAMP levels
D2- inhibitory- reduce cAMP levels
152
Why do antipsychotics have so many side-affects?
they lack specificity so act on a number of receptors
153
What functions is Noradrenaline involved with?
Sleep, Wakefulness and attention
154
Where's the main source of NA?
Locus Coeruleus
155
Does NA have many of few connections through the brain?
Many
156
Is adrenaline abundant in CNS?
No
157
Where is adrenaline produced in CNS?
clusters of neurons in the medulla
158
What class of receptors detect adrenergic NTs?
metabotropic
159
What is the neural role of Histamine?
Wakefulness, Appetite, memory
160
What class of receptors detect Histamine?
Metabotropic
161
What o antihistamines that cross BBB do?
act as sedatives e.g. promethazine blocks H1 and makes people sleepy
162
Where in the brain is histamine produced?
Tuberomammillary nucleus in the posterior hypothalamus
163
Name 3 functions of Serotonin
Mood, sleep, wakefulness, appetite, nausea
164
What clears Serotonin from synapses?
SERT (serotonin transporter)
165
What drugs target SERT?
SSRIs
166
What class of receptors are serotonin receptors?
All metabotropic except 5=HT3
167
Is Serotonin inhibitory or excitatory?
either- depends on cAMP regulation
168
Can multiple neuroactive peptides be released from a single vesicle?
yes
169
what class of receptors detect peptide NTs?
metaboptropic
170
Name 3 classes of peptide NTs
brain/gut peptides e.g. substance p, orexins
opioid peptides e.g. endorphins
pituitary peptides e.g. ACTH
171
Overall, what is synaptic plasticity?
increases or decreases in synaptic strength in response to synaptic activity
172
What is short-term plasticity?
Plasticity which lasts milliseconds to seconds, temporary and is related to NT release
173
What is synaptic faciliation?
When paired stimuli are given close together and the second PSP is greater than first due to increased Ca2+ has there has not been full closure of Calcium channel
174
As the interval between stimulations decreases, does synaptic facilitation increase or decrease?
decrease (calcium normalises between stims)
175
What is synaptic depression?
Where a train of stimulation, causes post-synaptic potential to decrease after each stimulus
176
Why does synaptic depression occur?
There's a finite supply of vesicles which reduce over repeated stimulation (if there's a gap in stimulation, it will recover as vesicle levels restore)- hence is short-term plasticity
177
What is long-term plasticity the basis of?
learning and memory
178
What are the 2 main forms of long-term plasticity?
Long-term potentiation- LTP
Long-term depression- LTD
179
Briefly describe the trisynaptic circuit in mice
inputs from entorhinal cortex, synapses onto dendate gyrus, projection to CA3 neurons, from here schaffer's collaterals synapse to CA1 neurons
180
Which aspect of the trisynaptic circuit in mice is studied in LTPresearch?
schaffer's collaterals to CA1 synapses
181
How is LTP studied?
Tetanic stimulation causing a greater induced response over time
182
What are the 4 properties of LTP?
-co-operative- crucial number of fibres must be simultaneously activated
- input-specific- synapse must be activated during induction
Associative- induction at concurrently active synapses
Hebb's Law- Spike-timing dependant plasticity
183
What is the mechanism underlying LTP?
It is NMDA receptor dependent, where high frequency stimulation causes prolonged depolarisation and alleviation of the Mg2+ block in NMDA receptors, increased Ca2+ activates kinase which causes the insertion of additional AMPA receptors from IC pool, synapses can now carry greater current
184
How has LTP been exhibited to remodel dendritic spines?
Glutamate uncaging studies indicated LTP being associated with the fast growth of new and already existing spines
185
Describe late-phase LTP and gene expression
Induction of LTP activates cell signalling pathways sending signals to the nucleus changing gene expression and activating CREB pathway to increase expression of plasticity. the earliest genes expressed are transcription genes themselves (e.g. c-fos) which go on to induce transcription of further proteins linked to plasticity
186
How is LTD induced?
prolonged low-frequency stimulation
187
What is the mechanism of hippocampal LTD?
a small and slow increase in calcium influx is triggered by the LFS, this activates phosphatase and leads to dephosphorylation of stargazin and endocytosis of AMPAR
188
Describe cerebellar LTD
When climbing and parallel fibres are simultaneously activated, LTD is seen in purkinje cells
189
What diseases does mutation in the SCN1A cause (VGSC)?
epilepsy, migraine, autism
190
what diseases does mutation in SCN2A cause (VGSC)?
epilepsy, ataxia, autism
191
what diseases does mutation in SCN3A cause (VGSC)?
epilepsy
192
what diseases does mutation in SCN9A cause (VGSC)?
either extreme pain or pain insensitivity (depending on up or down regulation)
193
What disease is linked to KCNA1 gene mutations in VGPCs?
episodic ataxia type 1
194
What disease is linked to KCNQ2, 3 and MA1 gene mutations in VGPCs?
epilepsy
195
describe the structure of voltage-gated calcium channels
a pore forming alpha-1 subunit and variation in other combinations of alpha, beta, gamma etc.
196
what does a mutation in CACNA1A gene cause (VGCC)
episodic ataxia type 2 and spinocerebellar ataxia type 6
197
what does a mutation in CACNA1B gene cause (VGCC)
myoclonus-dystonia syndrome
198
what does a mutation in CACNA1C gene cause (VGCC)
x-linked congenital stationary night blindness
199
what does a mutation in CACNA1H gene cause (VGCC)
childhood absence epilepsy
200
which class of drugs act on adrenergic receptors
beta-blockers e.g. propranalol
201
Name the drowsy antihistamine that crosses the BBB
Promethazine
202
Name a serotonin receptor agonist
sumatriptan (migraines), anxiolytics, LSD,
203
name a serotonin receptor antagonist
atypical antipsychotics, ondansetron (anti-emetic), SSRIs/ other antidepressants, clomipramine, fenfluramine, MAOI antidepressants
