Chapt. 2 - LTP Flashcards
A common, but now incorrect, view of memories and the brain is
that the brain was thought to be a warehouse, that memories could be stored away as items in the brain
What is the correct idea of how memories are acquired in the brain
the brain records/ represents experiences and certain ensembles of neurons are activated to acquire the memory. the neurons are later reactivated to retrieve that memory again
Cell assemblies
Donald Hebb proposed that they are modified ensembles of neurons and are the substrate (where they live) for memories.
It describes the network of neurons that are repeatedly being activated and therefore strengthening their connection
Why do neurobiologists believe that information about experiences can persist in a retrievable form
because the synapses (point of contact between neurons) can be modified by experience (strengthened/affecting probability of reactivating)
Explain plasticity as a mechanism
plasticity is not believed to be apart of memory itself, but a more general phenomenon of the nervous system. It is only a mechanism for acquiring and helping other structures to store that memory
Konorski and Hebb proposed what idea about plasticity
that the synapse was the critical site of plastic change
What rule did Hebb propose to specify how synaptic connections can be modified
with repeated firing between the same cells, some growth process or metabolic changes takes place in both cells and they become more efficient and stronger together.
cells that fire together, wire together
Memories from the brain’s view are…
the changes in the connectivity in the collection of neurons responding to an experience. the changes are not localized and are distributed among neural systems that are involved in memory producing processes/events
Connections between neurons are changed when…
the synapse that link them are modified
Why is it a challenging task to want to understand how modifications between synapses occur
requires locating neurons in the engram and their natural sensory inputs
simplified this task through the discovery of long-term potentiation
Define long term potentiation (LTP)
the persistent strengthening of synapses based on recent pattern activity. These patterns produce a long-lasting increase in signal transmission between neurons
What structure was mainly used while studying LTP and why
the hippocampus because of the well understand anatomy of the hippocampus. it makes it possibly to study connections between neurons in or region or subfield with neurons in another.
strategy (through the understanding of the trisynaptic circuit) = stimulate set of fibers known to synapse onto neurons in a particular subfield and record hat happens in that region when the impulse arrives
Trisynaptic circuit components
neurons in entorhinal cortex connect to dentate gyrus (region of hippocampus) through the perforant path
then neurons in dentate gyrus connect to CA3 pyramidal cells through mossy fibers
then neurons in CA3 connect to neurons in CA1 pyramidal cells through Schaffer collateral fibers
(this circuit of particular interest because allowed study of neurons between subfields)
these connections also had clear large fibre tracts
knew the order of the circuit
Experiment about question “is it possible to artificially modify the strength of synapses?”
Bliss and Lomo stimulated fibers in perforant path (neurons from entorhinal to dentate) recorded the synaptic activity in the dentate gyrus and found LTP.
applied weak stimulus and measured synaptic activity and same for strong stimulus.
then repeatedly presented the weak stimulus and found that it evoked a bigger response and this enhanced response is called LTP
LTP last for how long
at least several hours
LTP is an important discovery because it provided a way to study what
how synaptic strength can be modified by experience
In vitro preparation
dissect thin slice of tissue from hippocampus and placing it into chamber with chemicals in a solution to keep it alive for a few hours. then a stimulating electrode is positioned to deliver electrical current to a chosen set of fibers (usually schaffer collateral fibers and record CA1 response). the electrode measures
the (excitatory postsynaptic potential) EPSP, in the extracellular space
Define EPSP
excitatory postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential (high EPSP more likely to fire? therefore more LTP?)
What is the dependent variable when studying long term potentiation
fEPSP (field excitatory postsynaptic potential)
How is EPSP used to display/measure LTP
high frequency of stimuli so the same axons causes LTP which is shown by a long lasting increase in EPSP amplitude
A neuron is a ______, ____, ____, and _____ device
input device - receives chemical and electrical messages from other neurons
integrative device - combines messaged received from multiple inputs
conductive output device - sends info to other neurons, muscles, and organs
representation device - stores information about past experiences as changes in synaptic strength
A synapse is composed of
a presynaptic terminal (axon bouton) and a postsynaptic component separated by the synaptic cleft
What does the postsynaptic potential do in the postsynaptic current
it is excitatory or inhibitory potential that changes the excitability of the postsynaptic cell, caused by changes in membrane potential
what causes negative membrane potential
caused by different concentrations of positive and negative ions, different sizes of ion channels or permeability of the membrane, pumps, etc.
DUE TO CHANGES IN CONCENTRATION
membrane potential is ____ and can be driven either less or more _____
dynamic
negative
depolarization represents the case when the membrane potential becomes _____ and drives the neuron ____ generating action potentials
less negative (closer to zero)
towards
hyperpolarization represents the case when the membrane potential becomes _____ and drives the neuron ____ from generating action potentials
more negative
away
What is used to generate action potentials to produce LTP in the hippocampus?
electrical stimulation
Post synaptic depolarization
(ex. after electrical stimulation used to produce LTP to generate action potentials) resulting in synapses on the post synaptic neurons to depolarize. positive ions will flow into the neurons
Field EPSP
measure of the strength of a population of synapses and reflects the depolarization of many synapses.
What is the strength of synapses defined by
the change in transmembrane potential resulting from activation of the postsynaptic neurotransmitter receptors
What are the two ways to record postsynaptic potentials
intracellular electrode - penetrates neuron that detects positive ions flowing into the neuron to indicate depolarization.
electrode placed into extracellular fluid - measures electrical potential between extracellular fluid and a ground electrode
What is measured of the fEPSP to measure the strength of the synaptic connections
the slope of the fEPSP indirectly measures strength because fEPSP is the rate that positive ions flow away from the extracellular recording electrode and therefore the positive ions are entering the postsynaptic neuron and depolarizing.
Synaptic strength is measured by how much
postsynaptic depolarization is produced by the stimulus.
Increase is fEPSP represents and _____ in synaptic strength
increase
What are the waveform components from a recording electrode
- stimulus artifact - stimulus used to evoke action potential/triggering the current generator/electrode
- fiber volley - the action potentials generated by the electrical stimulus
- fEPSP - downward slope of the waveform, this is the positive Na leaving, meaning they are depolarizing
How is fEPSP calculated
represented as a % baseline.
difference between fEPSP produced by test stimulus during baseline period prior to inducing stimulus (T1) and response to test stimulus after inducing (T2)
T2/T1 x 100 = %
When testing using LTP methodology, the test stimulus serves what two functions
- establishes a baseline 2. used to determine if the inducing stimulus produced LTP
What is LTD (long term depression)
case in which synaptic activity weakens the strength of synaptic connections. delivery a low frequency stimulus for long period of time
Why was the phenomenon of LTP so interesting to learning and memory researchers
- cooperativity - requires cooperative interaction of afferent fibers in a system
- specificity - restricted to synapses activated (not all synapses that contact the same neuron)
- associativity - synapse which cannot produce LTP with weak input can undergo LTP when the synapse is coactivated via a strong input
What is done in order to produce LTP
experimenter applies electrical stimulation to axon fibers to cause release of nts to a populations of synapses on postsynaptic neurons
What does LTP represent
the strengthening of synapses activated by inducing the stimulus (increase in capacity of these synapses to influx positive ions in response to the test stimulus)
Define signaling cascade
a series of chemical reactions which occurs as a result of a single trigger reaction involved in synaptic modificiation
Define signaling cascade
a series of chemical reactions which occurs as a result of a single trigger reaction involved in synaptic modification
A signaling cascade is initiated by what
the first messenger - an extracellular substance (hormones or nts) that bind to a cell-surface receptor and initiates intracellular activity
What is the second step in a cascade
second messengers - relay signals from receptors on the cell surface to target intracellular proteins
What is the order of signaling cascades
first messenger –> second messenger –> proteins –> into both kinases and phophatases –> structural and functional proteins
Why are second messengers so fast and what does that allow for
synthesis of them do not depend on slower transcription and translation processes.
this allows for rapid production of second messengers which provide a way to amplify the effects of the first messengers inside the cell
Define kinases
proteins that can change the function of other proteins.
composed of inhibitory and catalytic unit
can be active or inactive state
What happens after a second messenger binds to the kinase
inhibitory unit is dissociated and kinase is in active state
in active state, catalytic unit can phosphorylate other proteins (add phosphate group) and change their function
Define phosphatases
proteins that remove phosphate groups
What is happening in the normal state of kinases
normally in its inactive state and the catalytic unit cannot phosphorylate other proteins
What are the three principles of LTP
- duration of LTP can vary
- duration of LTP depends on the set of molecular processes engaged by synaptic activity
- synapses are strengthened and maintained in a sequence of temporal, distinct but overlapping processes
What are TBS (theta burst stimulation)
high volume stimuli for short period. the number of TBS determines the duration of LTP
implies that synaptic strength can vary in duration and may have different molecular bases
(depends on TBS intensity which makes duration different)
What three general sets of molecular processes contribute to the durability of LTP
- post translation processes (assemble and rearrange existing proteins)
- transcription
- translation processes - generate new proteins
Sequence of molecular processes contribute to duration of LTP
high frequency stimulation –> synaptic activity –> biochemical interactions –> into both assemble: post translation modifications and generate: transcription and translation –> enhanced AMPA receptor function –> strengthened synapses –> LTP
Changes in synaptic strength that support LTP evolve in overlapping stages by unique molecular processes. what are these stages
- generation 2. stabilization 3. consolidation 4. maintenance
