Lecture 21- Communication Between Nerve Cells Flashcards
What is synaptic plasticity?
-Is a form of neuromodulation
-Defined as the activity-dependent modification of the strength (or efficacy) of synaptic transmission
Is synaptic plasticity as a form of neuromodulation short or long lasting?
Short or long-lasting
What processes does synaptic plasticity underly?
Underpins learning and memory
What are the two ways which we can study learning and memory? What are they each ideal for?
-in vitro= molecular and cellular events
-in vivo= behaviour
What are some examples of in vitro techniques?
- Cells in culture
- Acute brain slices
e.g. hippocampal slices (only last a few hours)
Organotypic brain slices (last a lot longer than hippocampal) - others
What are some examples of in vivo techniques?
- Simple invertebrate models
- Vertebrate rodent models
- Others
- Cellular events too
What are some advantages and disadvantages of in vitro techniques?
-Advantage= easy to apply drugs and see effect
-Disadvantage= true circuitry isn’t actually actually being reflected
What are two examples of Invertebrate models?
- Drosophila melanogaster
- Aplysia californica
What are the advantages associated with the Drosophila melanogaster invertebrate model?
Small genome and rapid life cycle
* Drosophila is good for genetics
* Small nervous system
* ~135,000 neurons
* Easy to identify and circuits
What are the advantages associated with the Aplysia californica invertebrate model?
- Small nervous system
- ~1,000 neurons
- Large neurons
- Easy to impale and record from
- Easy to identify individual neurons and
circuits
What is the Aplysia californica method for learning and memory?
Siphon-gill-withdrawal reflex:
* Tactile stimulus to siphon causes gill withdrawal
* This reflex undergoes habituation or sensitization (a simple form of learning)
when a noxious stimulus is applied.
What are the two types of Nonassociative learning than result in behavioural responses? Draw what neural activity looks like in these processes on a graph…
Habituation: learning to ignore a stimulus that lacks
meaning
vs.
Sensitization: Stimuli results in increased sensitivity
Graphs shown in slides (12)
What pattern of receptors/ what is happening at the neural level in the siphon-gill-withdrawal reflex?
-Touch activates sensory
neurons in the siphon skin
-Relayed to motor neuron
(L7) in abdominal ganglion
-Stimulates gill muscles and
thus gill withdrawal
What neural changes happen when habituation occurs?
-weakened neurotransmission
-decreased neurotransmitter release from sensory neuron
-fewer vesicles released per action potential
How is Sensitization demonstrated in the Aplysia?
When the siphon of Aplysia is gently touched, the animal withdraws its gill for
a brief period.
* But, if the “touch” is preceded by an electrical shock to its tail, the same gentle
touch to the siphon will elicit a longer period of withdrawal.
* If the Aplysia is given multiple shocks its subsequent response to a gentle
touch on the siphon is much larger and is retained longer.
What does Sensitization to a noxious stimulus delivered to the Aphysia’s tail require neurally?
- a sensory neuron that picks up the stimulus from the tail connecting to
- interneurons that terminate on the sensory neuron in the siphon-gill pathway.
What does Sensitization require?
Sensitization depends on increased synaptic activity, this process is called facilitation
What is presynaptic facilitation? (within the context of the gill withdrawal response)
- Stimuli results in increased sensitivity of the gill withdrawal response
- Noxious stimuli activate interneuron
- This enhances neurotransmitter release
from the sensory neuron presynaptic terminal
and - alters gene expression
What happens at the neuron/ molecule level in presynaptic facilitation as a result of a single tail shock to the Aphysia?
- L29 releases 5HT (serotonin)
- 5-HT (5-hydroxytryptamine receptors), serotonin
- activates 5HT receptors on presynaptic
nerve terminal - stimulates formation of cAMP
- activates protein kinase A (PKA)
!Release of neurotransmitter
What does PKA do in the context of presynaptic facilitation?
PKA increases phosphorylation of K+ channels:
-Phosphorylated K+ channels close
-K+ does not exit terminal as rapidly
-Prolonging the Action potential (limits repolarisation)
-Ca2+-channels increase their opening
What happens in presynaptic facilitation with regards to synaptic vesicles?
Increased mobilisation of synaptic vesicles
-via PKC
What does PKA do to calcium channels? and what is the result of this for the Aphysia?
PKA increases phosphorylation of Ca2+ channels
-voltage-sensitive Ca2+-channels open
-greater Ca2+ influx increases release of neurotransmitter
-stronger signal to motor neuron
-enhanced gill-withdrawal
What happens during presynaptic facillitation where the Aphysia receives multiple tail shocks as opposed to just one?
- L29 releases 5HT (serotonin)
- 5-HT (5-hydroxytryptamine receptors), serotonin
- activates 5HT receptors on presynaptic
nerve terminal - Higher levels of cAMP
- Activates protein kinase A (PKA) which
now moves to the nucleus
-Altered gene expression
-new proteins stimulate synapse growth
In vertebrate models what is long term potentiation?
-Long-lasting activity dependent increase in
synaptic responses
-Brought about by brief patterned high frequency stimulation to excitatory
pathways of hippocampus
When long term potentiation is induced in a rodent hippocampus what occurs?
-The hippocampus is a site of memory processing in rodents (know because they show impaired performance on learning and memory tasks following a hippocampal lesion)
-Trisynaptic loop occurs
What is the Trisynaptic circuit of the hippocampus?
- Entorhinal cortex → dentate gyrus (perforant path) synapses
- Dentate gyrus → CA3 (mossy fiber) synapses
- CA3 → CA1 (Schaffer collateral) synapses
What are some features of long term potentiation?
Elicited in brain regions associated with memory
* Synaptically-located
* Specific to active synapses
* Associative (ie. interactions between active inputs can influence its induction)
* Persistent
What mechanically/ neurological underpins long term potentiation?
Underpinned by increased glutamate receptor responsiveness
What are the two types Ionotropic Glutamate Receptors? What are the features of both types?
AMPA receptor subtypes
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor:
* Ligand-gated
* Mediate fast depolarisation
* Na+ channel
NMDA receptor subtypes
N-Methyl-D-aspartate receptor:
* Ligand and ion-gated
* Slightly slower response
* Not as slow as metabotropic receptors
* Ca2+ channel and Na+ channel
What is the structure of AMPA receptors in terms of how they sit across membranes?
-Have an extracellular domain, an intracellular domain and also lots of regulatory molecules attached
-They vary in composition according to their function
-There is complex network scaffolding across the membrane
Are receptors like islands?
No, they are more like trees with lots of routes and branches
In vivo does long term potentiation last a long or short time?
-Long, it last a really long time
What does long lasting change require and what does it result in?
-altered gene expression
-Happens via CREB phosphorylation
-Results in the growth of dendritic spines
What is a summary of LTP?
-Ca2+ influx into dendritic spine activates protein kinases
-Such as Ca2+-calmodulin-dependent protein kinase II
-phosphorylates the AMPA receptor to increase conduction
-AMPA receptors are trafficked to the membrane
- Protein kinase A (PKA), CaMKII
=long term changes to gene expression
