Synaptic Transmission & Neurotransmitters Flashcards
Axodendritic synapse
between the axon of a presynaptic neuron and a dendrite of a postsynaptic cell
Axosomatic synapse
between the axon of a presynaptic neuron and the cell body of a postsynaptic cell
Axoaxonic synapse
between the axon of a presynaptic neuron and the axon of a postsynaptic cell
Electrical potentials at synapses
- If the synapse is neuromuscular, axosomatic, or axodendritic, the flux of ions in the postsynaptic membrane generates a local postsynaptic potential.
- Axoaxonic synapse modulates the membrane potential of the postsynaptic cell (Presynaptic facilitation and inhibition)
Presynaptic Inhibition and Facilitation
- release of neurotransmitters from an axon terminal can be facilitated or inhibited by the chemical action at an axoaxonic synapse
- Axoaxonic synapses mediate presynaptic inhibition and facilitation
- Interneurons (as axoaxonic) regulate the ability of the presynaptic neurons to release neurotransmitters by changing the amount of Ca++ influx to the presynaptic neurons
Interneurons can…
- hyperpolarize or depolarize the presynaptic neurons
- This changes the amount of Ca influx to the presynaptic neurons.
- As a result, the ability of the presynaptic neurons to release neurotransmitters is modified.
Presynaptic Inhibition
- Interneuron releases neurotransmitters
- Neurotransmitters bind to presynaptic neuron, reduce Ca++ influx
- Presynaptic neuron releases less neurotransmitters when an AP arrives at its terminal
interneuron -> presynaptic neuron -> postsynaptic neuron
Presynaptic Facilitation
- Interneuron releases neurotransmitters
- Neurotransmitters bind to presynaptic neuron, increase Ca++ influx
- Presynaptic neuron releases more neurotransmitters when an action potential arrives
interneuron -> presynaptic neuron -> postsynaptic neuron
What is a Neurotransmitter?
- synthesized in the neuron
- transported to the presynaptic terminal
- released in amounts sufficient to exert an action on the postsynaptic neuron or effector organ
- removed from the synaptic cleft by a specific mechanism
Function of neurotransmitters
- excite or inhibit the postsynaptic neuron, depending on the molecule released & the receptors present on the postsynaptic membrane
- those that act directly are classified as fast acting, because their effects are extremely short
- those that act indirectly are classified as slow-acting, because their transmission requires 100 milliseconds to minutes
Direct activation of ion channels: ligand-gated ion channels
- Neurotransmitters bind to receptors that are part of the ligand-gated ion channels and directly open the ion channels.
- Ex: Na influx
- Fast acting
- Rapid/brief opening of membrane channels occurs when a neurotransmitter binds to the receptor site of the membrane channel
- Ion channel receptors act like a lock & key
Indirect activation of ion channels: G-proteins
- Neurotransmitters bind to receptors that are separated from the ion channels, & indirectly open the ion channels by activating the G-protein.
- involves changes in the metabolism of the cell.
- Slow acting
- activation of the G-protein elicits cellular events that develop slowly and last longer than the effects of ligand-gated channels
G-protein
can also cause persistent opening of membrane channels
What is a Neuromodulator?
- Act at a distance away from the synapse
- Modulate activity of many neurons at the same time
- Released into extracellular fluid
- Effects last minutes to days
Co-transmission of a neurotransmitter and a neuromodulator
Depolarization of the presynaptic terminal membrane -> events that result in the simultaneous release of neuromodulator (substance P) into the extracellular space & neurotransmitter (Glutamate) into the synaptic cleft
Neurotransmitters and Neuromodulators can be released…
at the same time
Medications/Drugs
When administered “exogenously” in reasonable concentration, medications mimic the action of the endogenously released neurotransmitters or neuromodulators exactly
Category: Amino Acid
Transmitter:
y-aminobutryric acid (GABA)
Glutamate (Glu)
The most prevalent fast-acting neurotransmitters are Glutamate (excitatory) and GABA (inhibitory).
(ligand-gated ion channels)
Amino acid: Glutamate (Glu)
- MAJOR Fast-acting excitatory neurotransmitter found in the CNS
- Involved in learning and memory
- Glutamate is present in a wide variety of foods, e.g. MSG
- Over-activity of glutamate may cause seizures
- Excitotoxicity: Excessive glutamate may produce neuronal damage or death, e.g. TBI or CVA
Amino acid: GABA
- MAJOR Fast-acting inhibitory neurotransmitter found in the CNS (e.g. inhibitory interneurons in spinal cord)
- Prevents excessive neural activity.
- Barbiturates mimics the action of GABA and are used for sedation or anticonvulsants.
- Baclofen, a muscle relaxant to control muscle spasticity, increases presynaptic release of GABA.
Cholinergic: Acetylcholine (ACh)
- MAJOR neurotransmitter in PNS, ANS, CNS
- Fast-acting effect: act at neuromuscular junction: Nicotinic receptors
- Slow-acting effect: regulate HR, ANS: Muscarinic receptors
- ACh has excitatory actions at the neuromuscular junction, at autonomic ganglion, at certain glandular tissues, and in the CNS.
- It has inhibitory actions at certain smooth muscles and at cardiac muscle
ACh receptors
-The structural difference between the nicotinic and muscarinic receptors
Nicotinic receptor
activation causes the opening of the postsynaptic receptor channel.
This increases the Na+ movement into the target cell, leading to depolarization and generation of the action potential (EPSP).
Muscarinic receptor
activation of postsynaptic cells can be either excitatory or inhibitory & is always slow in onset and long in duration
Nicotinic (summarized)
- Bind nicotine
- Linked to ion channels
- Fast and brief response
- Located at neuromuscular junctions, autonomic ganglia, and some CNS
- Mediate excitation
Muscarinic (summarized)
- Bind muscarine
- Liked to 2nd messenger system through G protein
- Slow and prolonged response
- Found on myocardial muscle, certain smooth muscle, in some CNS regions
- Mediate inhibition and excitation
Acetylcholine (ACh) functions as….
-a neuromodulator in CNS
–Controls…
Locomotion
Arousal
–Facilitate attention, memory, learning
Amines: Dopamine (DA)
- Produced in substantia nigra pars compacta of basal ganglia
- Primarily an inhibitory effect in the CNS
- All DA receptors are 2nd messenger systems to suppress the activity of Ca++ channels.
- Affects motor activity, motivation/reward behavior, and cognition
Dopamine Projecting System
- BG: movement
- Limbic: reward/wanting addiction
- Prefrontal: working memeory and attention
Neurologic Conditions: Dopamine
- PD:↓DA in basal ganglia
- Lack of motivated behaviors
- Depression/cognitive: ↓DA in forebrain
- Schizophrenia: too much DA
- Drug addiction: block the DA reuptake into the presynaptic neurons, allowing DA to activate receptors repetitively
Schizophrenia
- Pts w/ schizophrenia exhibit a variety of abnormalities of thought including delusions, hallucinations, disorganized, tangential speech; flat affect, & occasionally, a profound decrease in spontaneous activity called catatonia.
- Cognition, particularly working memory, is also often affected.
- Abnormalities in the limbic system, frontal lobes, and BG
- symptoms improve with antidopaminergic agents
Peptides: Substance P
-Neuromodulator
-Neuromodulator function in chronic pain syndrome
–increase pain perception
-Also released from some of the presynaptic sensory neurons
-Neurotransmitter function in the nociceptive pathway
stimulates free nerve endings at the site of injury & transmit pain signals from the periphery to the CNS
Peptides: Endogenous opioids (endorphin, enkephalin, dynorphin)
- Body’s natural pain killers
- Inhibit CNS neurons involved in the perception of pain
- Exercise increases endogenous opioids
