1
Q
What are the CNS systems that control behaviour?
A
- Autonomic nervous system
- Hypothalamic-pituitary neurohormones
- Diffuse monoamine system
2
Q
What drives behaviours?
A
Behaviours are driven by chemicals in the brain, or by chemical imbalances in the brain.
3
Q
What are the two behavioural responses of the ANS?
A
- Fight and Flight: activation of the sympathetic nervous system causing a surge of noradrenaline causing arousal
- Rest and Digest: activation of the parasympathetic system causing relaxation and recovery
4
Q
What are the molecules released from the brain in the diffuse modulatory system?
A
Monoamines
5
Q
What are monoamines? Give examples of monoamines
A
Monoamines are molecules released from the brain.
Noradrenaline, Serotonin (5-HT), dopamine and acetylcholine.
These systems together are called modulatory monoamine systems.
6
Q
How does the diffuse modulatory system work?
A
Small set of neurons at the core that project to many neurons of the brain. These arise from brain stem. One neuron influences many others. Synapses release transmitter molecules into extracellular fluid.
7
Q
Where do the noradrenergic neurons project from?
A
They project from the central core called the locus coeruleus.
8
Q
What do the noradrenergic neurons project to?
A
They project to the cortex, amygdala, spinal cord where noradrenaline is released to cause a biological effect.
9
Q
What are the four main diffuse modulatory systems?
A
- Noradrenergic Locus Coeruleus (Noradrenaline)
- Serotonergic Raphe Nuclei (Serotonin)
- Dopaminergic Sunstantia Nigra and Ventral tegmental area (Dopamine)
- Cholinergic Basal Forebrain and Brain Stem complexes (Acetylcholine)
10
Q
Describe whats involved in fast point-to-point signalling
A
- Neurotransmitters act on receptors, producing excitatory or inhibitory potentials
- Neuromodulators released from glial cells (particular astrocytes). Glial cells known as inexcitable neurons.
- Ligand-gated ion channels
- Glutamate (acts via ligand-gated receptors, and also through G protein receptors), GABA, Ach
11
Q
Describe whats involved in slow transmission
A
- Neurotransmitters and neuromodulators
- G-protein coupled receptors
- Monoamines, peptides and Ach
12
Q
Why does the CNS have more complex transmission principles than the periphery?
A
Transmission principles are the same as in the periphery; CNS is made more complex because of the interconnections between neurons and also the fact that other cells e.g. Glial cells also release mediators. Longer term changes affect the balance between these systems.
13
Q
What does the noradrenergic system release and how does it work?
A
Consists of noradrenergic neurons that release NA, projects from the central core: Locus Coerulus (LC), to different regions of the brain including the cortex, the amygdala, the hypothalamus down to the spinal cord, and the cerebellum.
14
Q
What is the effects of noradrenaline?
A
- Released in the brain and will induce a hyperarousal state that allows quick-thinking and needed for survival as well as acting on the heart.
- Important also in affecting the CVD system, increasing heart rate and blood pressure; this is a central effect.
- Important in addictive like behaviour; impulsivity is felt before this behaviour due to the noradrenergic surge.
15
Q
What is the locus coeruleus?
A
It is also known as ‘blue spot’ because of pigmentation
16
Q
How do the noradrenergic receptor synapse work?
A
- Noradrenaline is in the synaptic vesicles and then they release NA in the synaptic middlle.
- Then, NA will bind to post-synaptic G-coupled receptors.
- It will bind but will also activate pre-synaptic receptors (alpha-2 receptors).
17
Q
What are the alpha-2 receptors called?
A
They are autoreceptors
18
Q
What are autoreceptors?
A
When NA binds to them, they activate the autoreceptors and will inhibit the release of NA mediating the release of NA.
19
Q
What do the post-synaptic neurons do when NA binds to them?
A
Carry on the message
20
Q
What do the pre-synaptic neurons do when NA binds to them?
A
They are the autoreceptors that are usually inhibitory and have a negative feedback mechanism
21
Q
What conditions can happen if there is too much NA?
A
Addiction
Gambling
High blood pressure
22
Q
What conditions can happen if there is too little NA?
A
Depression
Low moods
23
Q
Explain how NA regulation is done
A
- Neurons regulate via the re-uptake mechanism using Noradrenaline Transporters (NET)
- Role is to uptake excess NA inside the neuron and this will be broken down by monoamine oxidase (MAO)
24
Q
Function of Reserpine
A
Depletes NA stores by inhibiting vesciular uptake
25
Function of Amphetamine (indirect sympathomimetic)
Enters vesicles displacing NA into cytoplasm, increase NA leakage out of the neuron.
26
Function of Cocaine
Blocks NA reuptake
27
Theory of why depression is caused
Caused by low levels of noradrenaline. Investigation was done by increasing noradrenaline. This was done by drugs that block the noradrenaline transporter or a drug that blocks monoamine oxidase.
28
Function of noradrenaline
Arousal, wakefulness, exploration and mood
Blood pressure regulation
Addiction/gambling
29
How do the cell bodies in the LC act?
LC neurons silent during sleep and activity increases with arousal especially in response to unfamiliar and threatening stimuli
30
How are the noradrenergic synapses form part of the baroreceptor reflex pathway?
In the medulla form part of the baroreceptor reflex pathway which regulates blood pressure
31
How are the noradrenergic synapses part of the limbic system?
They play a role in the reward system and are implicated in drug dependence.
32
What are the dopaminergic pathways?
- Nigrostriatal pathway
- Mesolimbic pathway
- Mesocortico pathway
- Tubero-hypophyseal pathway
33
Which conditions is dopamine involved in?
```
PD
Schizophrenia
Addiction
Emesis
ADHD
```
34
What is the nigrostriatal pathway?
Contains dopaminergic neurons that project from the substantia nigra to the striatum of the brain where dopamine is released to induce control/initiation of voluntary movement
35
How does parkinson's develop?
In neurodegenerative conditions, such as Parkinson's, the main reason they develop these symptoms is because these neurons in the striatum start to die and less dopamine is released. There is suppressed movement
36
What is the mesolimbic pathway?
Consists of the dopaminergic neurons that project from the VTA to different regions such as the amygdala as well as the nucleus accumbens. This induces the release of dopamine in these regions.
37
Function of the amygdala
Controls emotion control
38
Function of the nucleus accumbens
Important role in rewards such as food, sex, pleasureable behaviours - activates the mesolimbic pathway.
39
How does drug abuse hijack the mesolimbic pathway?
It stimulates the reward pathway more releasing more dopamine increasing pleasure even more leading to addiction.
40
What is hyperactivity of the mesolimbic pathway thought to cause?
Studies imply that psychotic like behaviour, some associated with schizophrenia (psychosis) experienced is due to hyperactivity of this pathway.
41
What is the mesocortico pathway?
It projects from the VTA to the cortex
42
What is the tubero-hypophyseal pathway?
Dopamine is released from neurons to activate neighbouring neurons but also can act as a neurohormone. It is released from the hypothalamus directly into the blood circulation, the portal system.
43
What happens when dopamine is released from the tubero-hypophyseal system?
- It will go to the pituitary and inhibit the release of prolactin. This is important for milk production.
- Dopamine is also important in vomiting such as the chemoreceptor trigger zone
44
Describe the formation of dopamine
Tyrosine that is metabolised by tyrosine hydroxylase to form L-DOPA, which is then metabolised by DOPA decarboxylase to form dopamine
45
What happens after L-dopa is metabolised to form dopamine and packaged into vesicles?
Dopamine is then released into the synapse and act on post synaptic receptors, D1 and D2, but there are also autoreceptors on the pre-synaptic neuron. When dopamine binds to these receptors, it inhibits the release of dopamine.
46
What conditions happen when there are too much dopamine?
Schizophrenia
| Addiction
47
What conditions happen when there is too low dopamine?
Parkinson symptoms
| Impairments
48
What reuptakes dopamine?
It is taken back into the neuron by DAT (dopamine reuptakers). This will take dopamine back into the neurons and is broken down by Monoamine Oxidase B (MOAb).
49
What is the mechanism behind schizophrenia?
Blocks D2 dopamine receptors and this is how anti-psychotics work
50
What are the dopamine receptor families?
D1-like receptor family:
- D1 and D5
D2-like receptor family:
- D2, D3 and D4
51
Structure of dopamine receptors
- 7 transmembrane domains
- GPCR
- Extracellular N-terminus
- Intracellular C-terminus
52
What happens when dopamine binds to D1 receptors?
- These receptors are Gs coupled receptors.
- When binding dopamine to D1, this will increase cAMP, increase pKa and then add phosphate group to DARPP-32. This will stimulate multiple receptors
53
What happens when dopamine binds to D2 receptors?
- These receptors are Gi coupled receptors.
| - Produce the opposite effect as they are inhibitory receptors
54
What structure do D1 and D2 receptors form?
They form heterodimers. They interlink structurally and functionally to form heterodimers that are usually Gq coupled receptors causing phosphorylation of IP3 and DAG to form PKC.
55
Where are D1 and D2 receptors located?
They are located in the striatum, limbic system, thalamus and hypothalamus.
56
Where are D3 receptors located?
Located in the limbic system not the striatum
57
Where are the D4 receptors located?
In the cortex and limbic system.
58
Why does dopamine induce nausea and vomiting?
The chemoreceptor trigger zone has a high density of D2 receptors DA agonists will induce nausea and vomiting.
59
What is the serotonergic system?
Serotonin is released from the serotonergic neurons that project from the raphe nuclei where the cell bodies are found and project to different regions of the brain such as the cortex, the cerebellum, the striatum, the hypothalamus and the hippocampus where serotonin is released.
60
What happens when there is an increase in serotonin?
In the cortex - leads to heightened perception
In the hypothalamus - reduced appetite
In the amygdala - elevated mood
61
Synthesis of serotonin
Formed from the precursor molecule tryptophan. This is metabolised by trypthophan hydroxylase which then forms 5-hydroxytryptophan. This is metabolised to serotonin
62
Where does tryptophan come from?
It comes from food because it is an essential amino acid that the body cannot produce.
63
Describe the mechanism of serotonin in the receptor synapse
It is packaged into vesicles then released into the synaptic cleft and acts on different types of receptors. It can also act on pre-synaptic autoreceptors.
64
What happens when the serotonin autoreceptors are activated?
If they are activated it will inhibit the release of serotonin. This is important to regulate serotonin in the synapse
65
What happens if there is too much serotonin?
Psychotic-like effects such as hallucinations
66
What happens if there is low serotonin?
Depression
67
What is the serotonin reuptake system?
It is taken back up by SERT (serotonin transporter) which transports serotonin inside the neuron where it is broken down by MAO. This terminates the action of serotonin.
68
How many types of serotonin receptors are there?
```
7
5-HT1
5-HT2
5-HT3
5-HT4
5-HT5
5-HT6
5-HT7
```
69
What type of receptors are the serotonin receptors?
Theyare all GPCR apart from the 5-HT3 receptor which is an ion channel receptor.
70
What do autoreceptors do?
They inhibit cell firing and transmitter release at the terminal regions.
71
What transporter takes dopamine back into vesicles?
vMAT2
72
Structure of the monoamine transporters
- 12 transmembrane domain pores
- Both ends intracellular
- Pumps monoamines into neurons
73
What are the two main diffuse modulatory cholinergic systems?
- Nucleus basalis
| - Septohippocampal pathway
74
What is the nucleus basalis cholinergic pathway?
Project from the nucleus basalis where the cell bodies are found to the cortex where acetylcholine is released.
75
What is the septohippocampal cholinergic pathway?
Projects from the septum to the hippocampus. This is important in cognitive function and motor control. Cholinergic interneurons are also found in the striatum (motor control).
76
What happens if there is degradation of the cholinergic neurons? What can be done to treat this disease?
Causes neurodegenerative conditions such as Alzheimer's and Dementia. Block Acetylcholinesterase so that Ach isn't broken down and the levels are increased. This is done by anti-cholinesterase inhibitors.
77
Describe the formation of acetylcholine
Choline and CoA come together to form Acetylcholine.
78
What happens to acetylcholine after it is formed in the synapse?
They are packaged into vesicles and are released into the synapse. It will then act on post-synaptic receptors. The types are: muscarinic (metabotropic) and nicotinic (ionotropic).
79
What breaks down Ach?
Acetylcholinesterase breaks down Ach to choline and acetate.
80
Which brain regions is acetylcholine abundant?
In basal forebrain, hippocampus and striatum
81
What is the function of Ach in the muscarinic receptors?
M1 excitatory (decrease M1 receptors in dementia)
M2 presynaptic inhibition (inhibit Ach release)
M3 excitatory glandular/smooth muscle effects (side effects)
M4 and M5 function is not well known
82
Functions of Ach
- Arousal
- Epilepsy (mutations of nAChr genes)
- Learning and memory (KO mice)
- Motor control (M receptors inhibit DA), pain, addiction
- Involved in schizophrenia, ADHD, depression, anxiety, Alzheimer's
83
What are three other transmitter/modulator substances?
- Histamine
- Purines
- Neuropeptides
84
What are the two types of histamine?
H1 (arousal) and H3 (pre-synaptic/constitutively active)
85
Functions of histamine
- sleep/wake and vomiting
- Minor transmitter in the brain but does have significant effects. Histamine cell bodies in the hypothalamus and have axons to most areas of the brain.
86
Types of purine
Adenosine (A1, A2a/2b) and ATP (P2x)
87
Uses of purines
In caffeine - adenosine antagonist promotes wake
88
Functions of purine
Sleep, pain, neuroprotection, addiction, seizures, ischaemia and anticonvulsant
89
Examples of neuropeptides
- Opioid peptides
| - Tachykinins (Substance P, neurokinin A and neurokinin B)
90
Functions of neuropeptides
Pain
91
What are the four opioid receptor types?
- MOP
- DOP
- KOP
- NOP
92
What are the three classical receptors and how where they identifed?
Mu, delta, kappa originally identified by homology screening.
93
What molecules act on the opioid receptors?
- POMC forms B-endorphin and binds to MOP and DOP
- Proenkephalin forms enkephalins that binds to DOP
- Prodynorphin forms dynorphins that binds to KOP
- Pronociceptin forms Nociceptin/OFQ that binds to NOP
94
Pronociceptin forms nociceptin. What else does it form?
Nocistatin that is an antagonist at the NOP receptors
95
How are neuropeptides synthesised and released?
The genetic codes for these proteins are found in the nucleus. mRNA is formed and protein synthesis occurs. Then, it is transported to the golgi apparatus which causes cleavage and releases the neuropeptide into the synapse
96
Which region of the brain is there a lot of opioid receptors?
- Nucleus accumbcens as it is important for rewards so opioids bind here.
- Thalamus is important for pain releif so morphine binds here.
97
Give examples of other transmitter/modulator substances
- Lipid mediators
- > Products of conversion of eicosanoids to endocanabinoids
- > Act on CB1 (inhibit GABA, glutamate release)
- > Involved in vomiting (CB1 agonist blocks it - MS, pain, anxiety, weight loss)
- Melatonin
- > Acts on MT1 and MT2 receptors
- > Involved in sleep regulation, circadian rhythmicity, agonists for jet lag and insomnia.
98
How does psychostimulants like amphetamine affect the monoamine system?
- Hypersecreting dopamine
- Displaces dopamine out of the vesicle that then leaks and there is a big surge of dopamine in the brain.
- There is a huge excitation etc.
99
Examples of amphetamine like drugs
Methylphenidate and MDMA
100
Pharmacological effects of psychostimulants
- Increased alertness and locomotor stimulation - increased aggression
- Euphoria/excitement
- Stereotyped behaviour
- Anorexia
- Increased physical and mental fatigue (improves monotonous takes)
- Peripheral sympathomimetic actions
- Confidence improves
101
Therapeutic uses of psychostimulants
ADHD (methylphenidate), appetite suppressants, narcolepsy
102
How does cocaine work?
It is a psychostimulant.
- It increases noradrenaline, dopamine and serotonin.
- Does this by blocking the reuptake transporter.
- This means there is accumulation in the synapse so a psychostimulant effect.
103
Pharmacological effects of cocaine
- Euphoria
- Locomotor stimulation
- Heightened pleasure
104
Pharmacokinetics of cocaine
HCL salt, inhaled and i.v. administration
Nasal inhalation leads to necrosis of nasal mucosa.
Freebase from ('crack') smoked as intense as i.v. route
Neuro
flashcards
Decks in class (20)
# Cards
-
Introduction to Clinical Neuroscience52
-
Structure of the Nervous System (Cranial Nerves)70
-
Neurons and Glia66
-
Glutamate57
-
GABA and Glycine48
-
Monoamines104
-
Neurohormones89
-
Vision82
-
The Chemical Senses46
-
Auditory and Vestibular Systems79
-
Sleep53
-
Somatosensation84
-
Motivation61
-
Learning and Memory60
-
Control of Movement41
-
Depression48
-
Emotion35
-
Anxiety41
-
Schizophrenia31
-
Language34
