Lecture 4: NEUROMODULATORS Flashcards
Define Neuromodulation
A change in the state of a neuron or a group of neurons that alters its response to a subsequent stimulation
Neuromodulators commonly act on
the release of neurotransmitters from
the axon terminals/presynaptic neuron and/or postsynaptic receptors
2 type of Neuromodulation… techniques..
A: Point-to-point neurotransmission
vs
B: Neuromodulation and volumetric neurotransmission
A: Point-to-point neurotransmission
vs
B: Neuromodulation and volumteric neurotransmission
A:
- INHIBITORY
Presynaptic neuron = depolarisation
….
Postsynaptic neuron = hyperpolarisation
or
2. EXCITATORY Presynaptic neuron = depolarisation
….
Postsynaptic neuron = depolarisation
B: Look at slide 3
Most neuromodulators bind to….. and therefore….
Most neuromodulators bind to ‘GPCRs’ and therefore …
-act on a slower timescale relative to neurotransmitters that bind to ionotropic receptors
Most neuromodulators bind to GPCRs and therefore act on a slower timescale relative to neurotransmitters that bind to ionotropic receptors
Well known examples include 5
- acetylcholine,
- dopamine,
- serotonin,
- cannabinoids,
- nitric oxide
what do neurotransmitters and neuromodulators bind to? 2
- Many neurotransmitters and neuromodulators bind to ‘GPCRs’
- Some neurotransmitters and neuromodulators bind to:
“ ion channels (ionotropic) and GPCRs (metabotropic)”
NEUROMODULATORS:
EXPLAIN RECEPTORS AND STRUCTURAL FEATURES
CLASS A: rhodopsin family
Receptors:
1. LARGEST GROUP
2. RECEPTORS: for most AMINE NEUROTRANSMITTERS, many NEUROPEPTIDES, PURINES, PROSTANOIDS, CANNABINOIDS, etc.
STRUCTURAL FEATURES:
1. Short extracellular (N-terminal) tail
2. LIGAND binds to TRANSMEMBRANE HELICES (AMINES) OR to EXTRACELLULAR LOOPS (PEPTIDES)
NEUROMODULATORS:
EXPLAIN RECEPTORS AND STRUCTURAL FEATURES
CLASS B: secretin/glucagon receptor family.
RECEPTORS: for PEPTIDE HORMONES, including SECRETIN, GLUCAGON, CALCITONIN
STRUCTURAL FEATURES:
1. Intermediate Extracellular tail incorporating ligand-binding domian
NEUROMODULATORS:
EXPLAIN RECEPTORS AND STRUCTURAL FEATURES
CLASS C: metabotropic glutamate receptor/calcium sensor family
Receptors:
1. SMALL GROUP.
2. METABROTROPIC GLUTAMATE RECEPTORS
3. GABA (b) receptors
4. Ca+2 SENSING RECEPTORS
STRUCTURAL FEATURES:
1. LONG extracellular tail incorporating ligand-binding Domain
Explain the 2 Stages of Neuromodulators
- RESTING STATE
- G proteins coupled to receptors - Agonist bind to GPCR
- G proteins coupled to receptor separate and interact/bind with their targets
draw and label the 2 Stages of Neuromodulators
slide 6
What are the roles and characteristics of adenosine in the brain? = 5 and explain
- Sleep Regulation and Energy Metabolism:
Adenosine regulates sleep homeostasis and energy metabolism in neurons. - Neuromodulatory Function:
It acts as a powerful neuromodulator in cholinergic neurotransmission in the brain. - Metabolite of ATP Degradation:
Adenosine is a metabolite of intracellular ATP degradation, increasing during high periods of neuronal activity. - Production Mechanism:
ATPases in the membrane degrade released ATP to produce adenosine, which is not stored in vesicles. - Receptor Binding:
Adenosine binds to G protein-coupled receptors (GPCRs), specifically AxARs, both pre- and postsynaptically, as well as on glia.
How does adenosine exert its neuromodulatory effects, specifically through A1 adenosine receptors (A1ARs), on cortical pyramidal neurons? = 3
- ‘Neuromodulatory Mechanism’ :
- A1 adenosine receptors (A1ARs) hyperpolarize cortical pyramidal neurons. - ‘Effect on Potassium Channels:’
- A1ARs increase the probability of potassium channel opening. - ‘Effect on Glutamate Release’ :
- They decrease the release of calcium-dependent glutamate by reducing the probability of calcium channel opening.
What is acetylcholine’s role as a neurotransmitter in the periphery? = 2
- Neuromuscular Junction:
- Acetylcholine (ACh) serves as the primary excitatory neurotransmitter at the neuromuscular junction in the periphery.
What role does acetylcholine play as a neuromodulator in the brain? = 2
- Cholinergic Neurotransmission:
- In the brain, acetylcholine acts as a powerful neuromodulator in cholinergic neurotransmission.
How does acetylcholine affect neurotransmitter release, and what factors influence its impact on neural activity? = 2
- Impact on Neurotransmitter Release:
- Acetylcholine tends to increase neurotransmitter release but can either promote or decrease neural activity depending on the system and the neuronal subtype it acts on.
What are some suggested roles of acetylcholine neuromodulation in the brain? = 3
Suggested Roles:
- Fine-tuning circuits for “uncertainty.”
- Reinforcing neuronal loops and cortical synaptics during learning.
- Fear conditioning.
Where are acetylcholine receptors located in the brain, and what are the main types of receptors? = 4
- Location:
Acetylcholine receptors are found both pre- and postsynaptically in the brain. - Types of Receptors:
Acetylcholine signals through - muscarinic (mAChRs) and
- nicotinic (nAChRs) receptors.
What are the neuromodulatory actions produced by muscarinic acetylcholine receptors (mAChRs)? = 2
- Neuromodulatory Actions:
- ‘mAChRs produce a range of neuromodulatory actions in the brain’
How do presynaptic M2/M4 mAChRs affect cholinergic terminals, and what is their impact on glutamate release? = 4
- Impact on Cholinergic Terminals:
…2. Presynaptic M2/M4 mAChRs inhibit cholinergic terminals through autoreception. - Effect on Glutamate Release:
….4. They reduce glutamate release.
What are the effects of M1/M5 mAChRs on dopamine release and cortical pyramidal neurons? = 4
- Dopamine Release:
2…. M1/M5 mAChRs promote dopamine release in the striatum. - Impact on Cortical Pyramidal Neurons:
4….. They increase the excitability of cortical pyramidal neurons.
What are the characteristics and distribution of nicotinic acetylcholine receptors (nAChRs) in the brain? = 4
- Characteristics:
2….. nAChRs are non-selective excitatory cation channels. - Distribution:
….4. They are dispersed throughout the neuronal membrane, including pre- and postsynaptic regions, soma, and axons.
What is the difference in neuromodulation speed between nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs)?… 2
- Neuromodulation Speed:
2….. Neuromodulation via nAChRs is faster than that via mAChRs due to the ionotropic nature of nAChRs compared to the metabotropic nature of mAChRs.