Chemical Brain: Neurotransmitter systems Flashcards
What is a neurotransmitter
- Chemical neurotransmitters (NTs) carry a message across the synapse to the next nerve.
- Chemical Synapses: Occur between nerves and • other nerves,
- muscle or
- glands
- At the synapse there is a break in electrical transmission (the action potential cannot cross).
Describe how a neuro transmitter is released
- Neurotransmitters are synthesized from precursors under the influence of enzymes
- Stored in vesicles
- Neurotransmitter molecules that leak from their vesicles are destroyed by enzymes
- Action potential cause vesicle to fuse with synapse and release neurotransmitters
- Some of it binds with auto receptor and inhibit subsequent neurotransmitter release
- Rest of it bind to post synaptic receptors.
- Released neurotransmitters are deactivated either by re uptake or enzyme degradation.
Transmission at the synapse
- Transmission is uni-directional from the pre-synaptic neuron to the post-synaptic neuron.
- NTs diffuse across the cleft and bind to post-synaptic receptors.
- The effect on the post-synaptic neuron can be either excitatory or inhibitory.
Neurotransmitters are mainly
peptides or amino acids.
• Receptors determine
the effects of the neurotransmitter.
Excitatory neurotransmitters
Glutamate (CNS) Nitric oxide (CNS)
Inhibitory neurotransmitters
Glycine (spinal cord) GABA (CNS) Serotonin (CNS) Dopamine (CNS) Endorphins (CNS & PNS)
Both excitatory and inhibitory neurotransmitters
Acetylcholine (ANS & NMJ)
Noradrenaline
Acetylcholine
• Acetylcholine is released at Neuromuscular Junction and in Autonomic nervous system
• NT in Parasympathetic fibres (pre &post – ganglionic fibres)
• NT in sympathetic (pre- ganglionic fibres only)
• Ach receptors are:
• Nicotinic: found in NMJ and ANS pre-ganglionic neurons.
• Muscarinic: Found in post-ganglionic neurons of parasympathetic.
Clinical Note: Reduced in Alzheimer’s and myasthenia gravis
Acetylcholine at the synapse
Acetylcholine is synthesized in nerve terminals from acetyl coenzyme A (acetyl CoA, which is synthesized from glucose) and choline, in a reaction catalyzed by choline acetyltransferase (CAT)
the postsynaptic action of ACh at many cholinergic synapses (the neuromuscular junction in particular) are not terminated by reuptake but by a powerful hydrolytic enzyme, acetylcholinesterase (AChE). This enzyme is concentrated in the synaptic cleft, ensuring a rapid decrease in ACh concentration after its release from the presynaptic terminal. AChE has a very high catalytic activity (about 5000 molecules of ACh per AChE molecule per second) and hydrolyzes ACh into acetate and choline. As already mentioned, cholinergic nerve terminals typically contain a high-affinity, Na+-choline transporter that takes up the choline produced by ACh hydrolysis.
Noradrenaline
Present in some nuclei in the brainstem extending to the brain and spinal cord.
• The main NT in sympathetic postganglionic fibres
• Brings about fight and flight response
• Acts on adrenoceptors
• s1 receptors- myocardium- excitatory
• s2 receptors- smooth muscle relaxation
• α1 receptors – smooth muscle contraction
• Neurotransmitter and hormone, signals release of cortisol from adrenal gland
Noadrenaline at the synapse
After synthesis in the presynaptic terminal, norepinephrine is released into the synaptic cleft to bind post-synaptic receptors, undergo reuptake by the presynaptic neuron, or undergo degradation.
Glutamate
- Widespread in brain and spinal cord, excitatory
- Glutamate receptors found on neurons and on glial cells
- Important in cognition, memory and learning through synaptic plasticity (a change in synaptic strength in response to specific patterns of synaptic activity over time through pre & post synaptic changes)
- Glutamate is the precursor of GABA (allows for regulation)
involved in extraneuronal signalling to the islets of Langerhans (pancreas)
Gama-aminobutyric acid (GABA):
• Usually act locally
• Important postsynaptic inhibitor in the brain and spinal cord
involved in extraneuronal signalling to the islets of Langerhans (pancreas)
Serotonin
• Present in a small number of nuclei in the brain stem whose tracts extend through the brain and spinal cord
• Inhibitory
Clinical Note: involved in mood, anxiety and sleep induction, (levels are elevated in schizophrenia). Too little serotonin can lead to anger and depression.
Dopamine
• Present in a small amount of nuclei and nerve tracts and some ANS synapses
• Excitatory
• Induces the feeling of pleasure
• Involved in reward pathway to reinforce behaviours (e.g. eating when hungry)
Clinical Note: Parkinsons disease results from a destruction of dopamine secreting neurons leading to a reduction in voluntary motor control.
Endorphins
• Widely distributed in the CNS and PNS
• Inhibitory
• Released in response to stress, exercise and some foods • Can trigger the release of dopamine
Clinical Note: Opiate morphine binds to endorphin receptors on presynaptic neurons blocking release of NT to block pain
Agonists
-make transmission of nerve impulses more likely. They prevent
reuptake of neurotransmitter (e.g. Prozac and cocaine).
• triggering the receptor themselves (nicotine)
• making the receptor more responsive (anti-anxiety drugs).
Antagonists
- interfere with nerve transmission across the synapse
• blocking receptor sites (spider and snake venom)
• preventing release of the neurotransmitter from the presynaptic terminal (many anti-psychotic drugs).
Neurotransmitter blockers
- Drugs- antidepressants, muscle relaxants, nerve gas
- Toxins- botulinum toxin, snake venom
- Alcohol, opiates (morphine), cocaine, nicotine, caffeine, amphetamines, cannabis, ecstasy
Clinical Note: local anaesthetics such as Novocaine decrease membrane permeability to Na+ preventing EPSPs and hence blocking action potentials and sensory input to the CNS
Summary of Neurotransmitter systems
Neurotransmitter synthesised in the cell body, in the axon, or in the axon terminal.
• Neurotransmitter stored in granules or vesicles in the axon terminal.
• Calcium enters the axon terminal during an action potential, causing
release of the neurotransmitter into the synaptic cleft.
• The transmitter binds to and activates a receptor in the postsynaptic membrane.
• Deactivation: Neurotransmitter is either destroyed enzymatically, or
taken back into the nerve terminal to be reused, or degraded.
• Many categories of neurotransmitter that have different effects according to their receptors
