Describe sensory memory
- large capacity, but rapid decay
- sensory association areas involved
Describe short-term (working) memory
- lasts for seconds to minutes
- severely limited capacity
- available to conscious awareness
- prefrontal cortex involved
Describe intermediate-term memory
- lasts for hours and days
- may be transferred to LTM through rehearsal
What are the two types of long term memory?
Explicit (declarative) and implicit (non-declarative)
Describe declarative memory
- involves hippocampus and medial temporal lobes
- neurons in hippocampus register info about the space surrounding an animal
- cognitive map of the external environment
What is synpatic plasticity?
Change in synaptic function in response to patterns of use
What is synaptic facilitization/sensitization?
Repeated APs result in increased Ca n terminal, increased NT release
What is synaptic depression/habituation?
Repeated APs deplete NT in terminal, decreased NT release
What was Eric Kandel’s model of choice?
Aplusia californica (Sea Hare)
Why did Kandel pick aplysia?
- small number of neurons
- large neurons
- culturable neurons that form circuits in vitro
- responses are visible and measurable
- respone triggered by several electrical synapses firing simultaneously
What was the main reflex Kandel studied?
Gill withrawal reflex
Describe the difference between habituation and sensitization.
- Habituation
- repeated stimulus leads to “ignore”
- “negative” memory - not stored
- Sensitization
- stimulus results in response
- results in consolidated memory
What is the simplest formation of implicit learning?
Habituation
Describe habituation in terms of neurons (aplysia?)
- size of EPSP by sensory neuon on motor neuron decreases in amplitude
- inactivation of calcium channels
- less Ca2+entering nerve terminal of presynaptic membrane
- less NT released
Describe sensitization in terms of neurons.
- large increase in amplitude of EPSP
- increase in amount of NT released
- amplification due to interneurons
Describe signalling by the interneurons (short term sensitization)
- excitatory interneurons release serotonin (5-HT)
- 2 serotonin receptors in Aplysia
- 5-HT2 like receptor
- PLC pathway
- 5-HT4,6,7 like receptor
- adenylate cyclase pathway
- 5-HT2 like receptor
Storage of long-term memory results in ___________ in the presynaptic termini.
Physical changes.
- Habituation
- retraction of presynaptic termini
- in aplysia, 35 fewer connections with motor neurons and interneurons
- Sensitization
- increase in number of connections
- in aplysia, 2 fold increase
What were the long term changes in habituation and sensitization in the aplysia?
- normal aplysia showed 1300 axon terminals on sensory neurons
- aplysia experiencing sensitization had 2800 terminals
- aplysia experiencing habituation had 800 terminals
Describe long term sensitization.
- cAMP binds to and activates CREB
- cAMP response element binding protein
- MAPK may also be involved
- CREB translocates to nuclues and increases gene expression of specific gene
- changes protein profile of synapse - changes in size etc.
What is the feedback loop involved in long term sensitization?
- one gene synthesized in response to CREB is ubiquitin hydroxylase
- degreade regulatory domain of PKA
- results in continuous activity of PKA
- Ks is continuously phosphorylated
- AP prolonged
- Ca influx almost permanent
- continued release of NT
What is BDNF?
Brain-derived neutrophic factor
- activated by NMDA receptor
- in aplusia, blocking BDNF - no long term memory
- corticosteroids decrease BDNF
- activates growth of dendritic spines
- role in generation/localization of new receptors
What test tested the spatial memory of vertebrates?
Morris water maze
What NT/receptor are used in learning pathways for vertebrates?
Glutamate
Does the learning pathway in vertebrates require an influx of Ca2+ into the post-synaptic cleft?
Yes
What 3 protein kinases does Ca2+ activate in the learning pathway of vertebrates?
- Calcium/calmodulin kinase
- PKC
- Tryosine kinase fyn
What is long-term potentiation? Where was it first measured?
Stumilation of pre-synaptic neuron leads to a long-term increase in the magnitude of EPSPs in post-synaptic neurons. First measure in hippocampal tissue.
What effect does LTP have on synapses?
LTP strengthens existing synapses and also creates new ones.
What is needed for LTP to occur?
Rapid rate/high frequency of stimulation.
What are the two types of LTP glutamate receptors?
AMPA and NMDA
Which LTP glutamate receptor is activated first?
AMPA; activated first, ionotropic, local depolarization events
NMDA is normally blocked by _____. And requires what typed of even to open?
Mg2+, requires depolarization event and Glu binding to activate.
AMPA receptor has ___ subunits and ___ agonist-binding sites.
4 and 4
What does NMDA stand for?
N-methyl-D-aspartate
What are the characteristics of NMDA?
- heterotetramer
- non-specific cation channel
- blocked by Mg2+ at RMP
- preferentually allows Ca2+ passage
What are the other two types of glutamate receptors? (Other than AMPA and NMDA)
Kainate and mGluR
Which of (non AMPA and NMDA) glutamate receptors is metabotropic?
mGluR
___________, activated by Ca2+ influx, is a mediator of downstream effects.
Calmodulin-dependent kinase (Calmodulin is activated by Ca, which then activates kinase).
What are the 2 main phases of LTP? Describe them.
- Establishment
- induced experimentally by single high-frequency stimulus
- invovles kinases but not protein synthesis
- Maintenance
- experimentally requires a series of high-frequency stimuli
- requires protein synthesis
What happens during early LTP (establishment)?
What happens in late LTP (maintenance)?
How does LTP change the pre-synaptic termini?
Increased synaptotagmin and number of SVs
What is synaptic tagging?
Protein tage present in active synapses. Direct localization of mRNA bundles.
What is the reverse of LTP?
Long term depression
What is LTD?
- decrease in dendrites/spines
- due to low frequency stimulation
- may be necessary for eliminating memory traces
- important in motor learning
Is the NT for LTD still glutamate?
Yes
LTD involves ______ and phosphorylation of _______.
MAPK and AMPA receptors