Task 3 Flashcards
Synaptic Plasticity
What ist Long-Term Memory from a neuronal perspective?
- an experience induced connectivity pattern in a neuronal network
- linking together even distant parts in the brain
How how can neural activity lead to changes in
the function and anatomical structure of
neurons?
• answers lies in the proteins and genes
inside neurons
What do proteins do?
- form signaling cascades that allow neurons to adapt to their input
- cascades link activity with –> connectivity
What are Immediate Early Genes (IEG)?
• expressed in reaction to Calcium influx during neuronal activity
–> produce transcription factors (proteins) that control expression of other so-called ‘late genes” (LGs)
What do Late Genes (LG) do?
• produce proteins that can lead to changes in synaptic connectivity
Early LTP
- A temporary strengthening of the synapse lasting hours
- can be triggered by a single strong co-activation
- is based on existing proteins
- requires no genomic response
Late LTP
- more permanent strengthening of synapses
- requires repeated strong co-activation
- requires new proteins (de novo protein synthesis)
- is dependent on a genomic response
Standard Theory of Memory Consolidation
- During an experience: distributed activity across the brain
- Cortical plasticity is slow, but hippocampal plasticity is fast.
- Some cells in hippocampus become linked to activated cells in the cortex
-hippocampus reinstates cortical activity patterns
to starts binding them into a memory of the experience
(hippocampus as a tutor)
- The hippocampus does this over and over again (e.g., every night),
and each time produces cellular consolidation and
plasticity in neuronal connectivity in the emerging memory trace. - At the end, the hippocampus is no longer necessary
–> Predicts GRADED Retrograde Amnesia
Problems with Standard Theory
This has important implications for episodic memory
- A spatial code in the hippocampus?
- Is the spatial environment not integral to any episodic
memory? - What does it suggest with respect to the role of the
hippocampus in long-term episodic memory?
This has led to a second systems consolidation theory of
episodic memory.
Multiple Trace Theory
After each retrieval of a memory, the memory
will be re-consolidated in a new form (new
trace)
• During consolidation, but also reconsolidation
the memory is vulnerable
– Interference during reconsolidation
• undesired memory loss (e.g., stress/cortisol, protein
synthesis inhibitors, a novel experience)
• Therapeutic opportunities
–> predicts flat retrograde amnesia
How multiple trace theory
explains the difference between
episodic and semantic memories
+ Episodic memories always come first (a
learning event in a rich context)
• Semantic memories are the results of
experiences that have become detached of
the rich context in which they were acquired
• Semantic memories ultimately do not require
the hippocampus.
Which lesions lead to
episodic memory loss?
Anterior Temporal lobe lesion including the
hippocampus will give deficits dominated by
anterograde and retrograde (episodic)
memory loss
Which lesions lead to
semantic memory loss?
Lesions in association cortex will give lesions
that may be more semantic in nature, and
may to some extent show modality specificity
(e.g., as in agnosia’s)
Conclusions on LTP
How can you study it?
LTM can be studied from the perspective of
- Cellular consolidation
- Systems consolidation
- Cognitive theories
- Neurophysiology (place cells)
- Anatomy
- Behavioral effects of lesions in patients
THE LTP PARADIGM ?
Hippocampus supports episodic memory of unique,
singular events
- Hippocampal-cortical connectivity related to LTP
- Hippocampal long-term memory then related to late-phase LTP
• Late-phase LTP requires 1) powerful input and 2) repeated
stimulation
• How does the brain solve this contradiction?
THE LTP PARADIGM!!
Multiple temporally coinciding small inputs can
lead to depolarization & LTP
• Hippocampal memory formation
includes simultaneous inputs from
different cortical locations
• Episodic memories are associative
experientially and neurobiologically
• Hippocampal-cortical connectivity reactivates during sleep/resting
Is LTP a good paradigm to study naturally
occurring plasticity?
Blocking NMDA receptors will block early and late LTP
- and does the same for natural learning and memory formation
- Blocking NMDA receptors will block early and late LTP
- And will block training-induced motor/somatosensory remapping
- Blocking the translation of proteins will block late LTP
- and will block long-term retention of natural learning and memory
- Blocking gene transcription will block late LTP
- and will block long-term retention of natural learning and memory
—> So the answer to the above question is: Yes
Spacing effect
- distributed learning enhances memory consolidation
- enough time for protein synthesis to occur necessary & determines the synaptic strengthening that depend on memory reactivation
Reactivating the Engram
.. in a nutshell
- Hippocampus receives input from cortical areas like somatosensory cortex or visual cortex
- uses Long Term Potentiation to create connections between cells in Hippocampus
- 6-12 hours later: Send information back to the original areas
• There also happens LTP, but cortical cells are now not activated by experience itself, but by the REACTIVATION OF THE ENGRAM
-> Hippocampus teaches cortical regions, that they were part of the same experience
Shift from ACTIVITY (working Memory) to CONNECTIVITY ( Hippocampus)
System Consolidation
- Changes in neuronal networks that are linked to memory storage
- How different neuron populations across the brain are activated by an event and then become linked to a cortical network with hippocampus as a teacher
Result: Creation of memory traces that entail contain a lot of memory components and can be retrieved as a whole
Cellular Consolidation
• Are the changes in synapses among the network that allow system consolidation
Early LTP
• single coactivation leads to more efficient synaptic tranmission between the two neurons
• presynaptic: exocytosis of vesicle with Glutamate more efficient
- postsynaptic: insertion of more receptors
CALCIUM responsible for both processes
What does Calcium influx lead to in the postsynaptic neuron? EARLY LTP
- When Glutamergic excitation in postsynaptic neuron high enough, Mg2+ molecule blocking the NMDA receptor is removed -> Calcium influx via NDMA receptors possible
- Calcium then is involved in inserition of additional glutamate receptors (AMPA) into membrane
What does Calcium influx lead to in the presynaptic neuron?
EARLY LTP
• calcium influx facilitates exocytosis of glutamate vesicles
The Dogma of molecular biology
• gene transcription into RNA & translation of RNA into proteins
What is necessary for memory formation?
- Sensory Experience that leads to coactivation
* presence and activity of genes that modulate Late LTP
LTP ≠ Plasticity
- Ltp is just a paradigm to experimentally study and manipulate neuronal plasticity
