Chapter 25: Molecular Mechanisms of Memory Flashcards
iIdentifying where and how different types of
information are stored
neurobiology of memory
Accdg. to (), Memory results from synaptic modifications
Hebb
Study of simple invertebrates (Kandel)
molecular mechanisms lead to ()
synaptic plasticity
process by which some experiences, held temporarily by transient modifications of neurons, are selected for permanent storage in long-term memory
not all memories are created equal
memory consolidation
virtually () in the nervous system can form am memory of recent patterns of activity
all neurons
macaque monkeys can be trained to discriminate images of objects and associate them with a food reward; however, they can lose this ability when lesions are made in the ()
inferotemporal cortex (contains Area IT)
Area IT = both a visual area and an area involved in memory storage
selective amnesia for familiar faces (including one’s own) that can result from damage to the inferotemporal cortex in humans
prospagnosia
like most cortical neurons, IT neurons typically show the property of ()
stimulus selectivity
concept that a memory is represented by a unique pattern or ratio of activity of neuronal activity; no single neuron represents specific memory
distributed memory
memory loss: instead of a catastriohic loss of any one memory as a result of damaged neurons, representations tend to blend together as nwueons are lost -> one memory gets confused with another
graceful degradation of memories
synapses store memories
the () that leads to memory can be the modification of synaptic weight
physical change
Eric Kandel’s study of Aplysia californica showed that simple forms of learning (habituation, sensitization) were accompanied by changes in ()
strength of synaptic transmission between sensory neurons and motor neurons
they were able to dissect many of the molecualr mechanisms that underlie these changes
2 traditional views in memory research
- chain of reactions (Pavlov and Thorndike)
- flashbulb memory (insight learning)
memories formed as APs pass through pathways multiple times -> gradually, pathways are strengthened
chain of reactions
Conditioning
“one try learning”; being able to commit something to memory after experiencing it just once
evidence that chains of reactions cannot explain everything about memory formation
flashbulb memory (insight learning)
responses to a situation which are followed by a rewarding state of affairs will be strengthened and become habitual
responses to that situation.
Law of Effect (Thorndike)
() was thought to explain Flashbulb memory
Hebbian synapses
Connections between neurons increase in efficacy in proportion to the degree of correlation between pre- and post-synaptic activity.
“Neurons that fire together, wire together”
“Neurons that aren’t in sync, lose their link”
Hebb’s Rule
Hebbian explanation for short term memory: neruons activate each other
reverberation
Hebbian explanation for transition into long-term memory: when there are (1) that happen between active neurons, a new (2) is formed
- metabolic process
- functional assembly -> changes in synaptic weight
pattern completion based on Hebbian response
patterns are completed because synapses are ()
strengthened
even though part of the image is given, we can recollect the missing parts from memory
pattern completion
- () studies have shown that associative memories can be stored in a network of neurons using Hebbian learning rule (Hopfield, 1984).
- () is important.
- () serve this function in the brain.
- Neural network
- Bidirectional connectivity
- Recurrent collaterals
recurrent collaterals are especially present in the () -> epilepsy due to overactivity in this region is very common
hippocampus
well-known example of short-term synaptic plasticity in the NMJ
post-tectanic potentiation (PTP)
increased response in PTP is due to ()
accumulation of Ca2+
brief stimulation resulting in long-lasting response can explain ()
one time learning
the hippocampus consists of 2 thin sheets of neurons folded onto each other
- dentate gyrus
- Ammon’s horn (cornu Ammonis, CA)
the entorhinal cortex (major input to HC) sends info to the dentate gyrus of the HC via a bundle of axons called ()
perforant path
dentate gyrus neurons give rise to axons called () that synapse on cells in CA3 (division of Ammon’s horn)
mossy fibers
one of the branches that stem from CA3 neurons is called () -> synapse on CA1 neurons
other branch leaves HC via the fornix
Schaffer collateral
where the most sophisticated understanding of LTP was found
LTP requires Ca2+ entry via (1); to open these, strong depolarization required to overcome (2)
- NMDA receptors
- Mg2+ block
NMDA receptor: coincidence detector (molecular switch)
property in which only the activ inputs show synpatic plasticity
input specificity
LTP induction is blocked by (1) and (2)
- AP5 (NMDA receptor blocker)
- EGTA (Ca2+ chelating agent)
mechanism of LTP in CA1: increased [Ca2+] activates PKC and CaMKII, which in turn cause (3)
- phosphorylation of AMPA-Rs -> increased membrane conductance
- Increased number of AMPA-Rs at terminal
- Formation of new synapses (via formation of postsynaptic dendritic spines)
(): synapses will undergo synaptic weakening instead of LTP when they are active at the same time the postsynaptic cell is only weakly depolarized by other input (1982).
BCM theory
Bidirectional plasticity of many cortical synapses governed by two simple rules
– Synaptic transmission during strong depolarization of postsynaptic neuron causes LTP.
– Synaptic transmission during weak depolarization of postsynaptic neuron causes LTD.
LTP can result when the EPSP caused by synaptic glutamate (excitatory) release precedes an AP in the postsynaptic neuron
spike timing-dependent plasticity
Mechanisms of LTD in CA1
Two forms of controllimg homosynaptic LTD at Schaffer collateral–CA1 synapse
– G-protein coupled metabotropic glutamate receptors (mGluRs)
– NMDA receptors
Rise in () is necessary to trigger LTD.
postsynaptic [Ca2+]
() accounts for bidirectional
synaptic changes (up or
down)
partial block on NMDA-Rs (modest, prolonged elevation of Ca2+)
() in the postsynaptic membrane are continually being added and removed (about every ~15 min)
AMPA receptors
determine capacity of postsynaptic membrane for AMPA receptors
slot proteins (PSD-95)
recent research suggests that the add’l receptors added to membrane during LTP contain ()
GluR1 subunits
First evidence of NMDA receptor-dependent processes in memory
Morris experiments using water maze
learning induces () in CA1
LTP
Homeostatic mechanisms needed to provide stability and keep synaptic weights within useful dynamic range
- metaplasticity
- synaptic scaling
Unchecked synaptic plasticity could lead to ()
unstable neuronal responses
further strengthening of synapses -> all synapses fully potentiated -> lose stimulus sensitivity0
- general idea that the rules of synaptic plasticity change depending on the history of synaptic or cellular activity
- Adjustments in composition of NMDA receptors
metaplasticity
metaplasticity
() increases in response to too much LTP (increased activity); same logic for too much LTD
synaptic modification threshold
metaplasticity adjusts (), which determines the properties of NMDA receptors
NR2A/NR2B ratio (subunits in NMDA receptors)
more NR2B = favor LTP
more NR2A = favor LTD
- adjustment of absolute synaptic effectiveness that preserves the relative distribution of synpatic weights
- Relative differences in synaptic strengths on a neuron are unchanged, even at the absolute levels go up or down
- Occurs over hours to days
synaptic (homeostatic) scaling
Other mechanisms needed for long-term consolidation
- Persistently active protein kinases
– Protein synthesis
Persistently Active Protein Kinases:
(): large increase in [Ca2+] allows autophosphorylation -> maintains “on” state
CaMKII
general idea that the an autophosphorylating inase could store information could store information at the synapse
molecular swtich hypothesis
in the context of CaMKII and LTP
– “() zaps established memories”
– Maintains changes in synaptic strength by continuing to phosphorylate substrates
ZIP (PKM-zeta inhibitor)
() required during the period of memory consolidation
New protein synthesis
when brain protein synthesis is inhibited, training of task is okay but no memory retention when tested days later
Experiments of Julietta Frey and Richard Morris
- Weak stimulation endows synapses with a ()
- Enables them to capture newly synthesized proteins that consolidate LTP
tag
with tag, an event that would otherwise be forgotten might be () if it occurs within 2 hours of a momentous event
that triggers a wave of new protein synthesis
seared into long-term memory
- Functions to regulate expression of neighboring genes (transcription factor)
- regulates gene expression required for memory consolidation (fruit fly).
CREB: cyclic AMP response element binding protein
– CREB-2 overexpression: (1)
– CREB-1 overexpression: (2)
- represses gene expression, blocks memory consolidation
- activates transcription, facilitates memory
