Synaptic Transmission & Neurotransmitters Flashcards
Types of synapses
Axodendritic
Axosomatic
Axoaxonic
Axodendritic
b/w axon of presynaptic neuron and dendrite of postsynaptic cell
Axosomatic
b/w axon of presynaptic neuron and cell body of postsynaptic cell
Axoaxonic
b/w axon of presynaptic neuron and axon of postsynaptic cell
Electrical potentials @ synapses
- Axosomatic & Axodendritic generate local post-synaptic potential
- Axoaxonic modulates membrane potential of the postsynaptic cell (Presynaptic facilitation and inhibition)
Presynaptic Inhibition and Facilitation
Axoaxonic synapses regulate presynaptic neurons to release NT by changing Ca++ influx to presynaptic neurons
Presynaptic Inhibition
1) Interneuron releases NT
2) NT bind to presynaptic neuron, reduce Ca++ influx
3) Presynaptic neuron releases less NT when an action potential arrives at its terminal
Presynaptic Facilitation
1) Interneuron releases NT
2) NT bind to presynaptic neuron, increase Ca++ influx
3) Presynaptic neuron releases more NTwhen an action potential arrives
What is a Neurotransmitter?
- synthesized in the neuron
- transported to pre-synaptic terminal
- released in amounts sufficient to exert an action on the post-synaptic neuron or effector organ
- removed from synaptic cleft by a specific mechanism (Synaptic vesicle cycling)
Function of Neurotransmitters
- excite or inhibit post-synaptic membrane
- depends on the molecule released and the receptors present
- act directly = fast acting and short-lived (Ligand gated theory)
- act indirectly = slow acting
Direct activation: Ligand-gated ion channels
- NT bind to receptors part of the ligand-gated ion channels and directly open the ion channels.
- Na influx
- Fast acting
- “lock and key”
Indirect activation: G-proteins
- NT bind to receptors and triggers action of G-protein
- G-protein then initiate process to open ion channels
- changes in the metabolism of the cell
- slow acting
- can also cause persistent opening of membrane channels
Signal transmission at G-protein
A. In the non-stimulated state, the αβγ–chain is associated with a membrane receptor.
B. NT binds to membrane receptor and activates G-protein. The α-chain detaches from the membrane receptor.
C. The (GTP) binds to membrane-spanning G-protein channel. Channel opens and Na flows in
D. The α-chain is inactivate and release from protein channel. Channel closes and the α-chain returns to its host membrane receptor to bind with the βγ-chain.
What is a Neuromodulator?
- Act at a distance away from the synapse
- Modulate activity of many neurons @ same time
- Released into extracellular fluid
- Last minutes to days
Co-transmission of a neurotransmitter and a neuromodulator
Depolarization of pre-synaptic terminal membrane triggers events that result in the simultaneous release of neuromodulator (substance P) into extracellular space and NT (Glutamate) into synaptic cleft.
Medications/Drugs (Exogenous vs. Endogenous)
When administered “exogenously”, medications mimic action of endogenously released NT or neuromodulators exactly.
Common NT’s and Neuromodulators
1) Amino acid: GABA and Glutamate
2) Cholinergic: ACh
3) Amine: DA
4) Peptides: Substance P
GABA and Glutamate
most prevalent fast-acting neurotransmitters
Ligand-gated channels
Amino acid: Glutamate (Glu)
- MAJOR Fast-acting excitatory NT
- Involved in learning and memory
- Glutamate is present in a wide variety of foods, e.g. MSG
- may cause seizures
-Excitotoxicity: Excessive glutamate may produce neuronal damage
Ex) TBI or CVA (Glu is 1000 X higher than normal)
Amino acid: GABA
- MAJOR Fast-acting inhibitory NT
- 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 pre-synaptic release of GABA.
Cholinergic: Acetylcholine (ACh)
MAJOR NT in PNS, ANS, CNS
Fast-acting effect
-@ neuromuscular junction: (Nicotinic receptors)
Slow-acting effect
-regulate HR, ANS: (Muscarinic receptors)
-Controls…
Locomotion
Arousal
Facilitate attention, memory, learning
Nicotinic vs Muscarinic
Nicotinic = bind nicotine, link ion channels, fast and brief, @ neuromusclular junction, mediate excitation
Nuscarinic = bind muscarine, linked to 2nd messenger through G-protein, slow and prolonged, @ myocardial muscle, mediate inhibition
Amines: Dopamine (DA)
- Produced in substantia nigra pars compacta of BG
- inhibitory effect in the CNS
- 2nd messenger systems to suppress the activity of Ca++
- Affects motor activity, motivation/reward behavior, and cognition
Dopamine Projecting System
BG = movement Limbic = reward/wanting addiction Prefrontal = working memory and attention
Neurologic Conditions: Dopamine
Parkinson’s disease
↓DA in basal
Schizophrenia
- delusions, hallucinations, disorganized, tangential speech; flat affect
- catatonia = decrease in spontaneous activity
- working memory is affected.
- Abnormalities in limbic system, frontal lobes, and BG
- S/S improve with antidopaminergic agents
- NT involved = glutamate, GABA, serotonin, and norepinephrine.
Peptides: Substance P
-Neuromodulator and NT
Neuromodulator in chronic pain syndrome
-increases pain perception
NT in the nociceptive pathway
-stimulates free nerve endings @ site of injury and transmit pain signals from PNS to CNS
Peptides: Endogenous opioids (endorphin, enkephalin, dynorphin)
Body’s natural pain killers
Inhibit CNS neurons involved in perception
Exercise increases them!
