Lecture 1 Systems Consolidation
One of the most fundamental idea’s of memory and
memory consolidation.
• Episodic = Memories about an event in your life
• Semantic = Facts
Memory Consolidation
Memory = the combined activity of a network that spans
a whole brain
• The hippocampus – Important for memory consolidation
• The Cortex – location the memory is stored
When you consolidate a memory you make it independent on the
hippocampus. Then it will be more dependant on certain area’s of the
cortex depending on the specific
When you are sleeping your brain sort through to see which memories
are important to keep and in what detail.
Memory consolidation – days to weeks
Cellular Consolidation Cellular Consolidation – in hours
Cells that wire together, fire together
1. When cells are activated at the same time
a lot the AMPA receptors activate and
depolarise
2. Mg block is gone from the NMDA
receptors and influx of Ca rapidly increase
3. CaMKII phosphorylates AMPA receptors
and stars a cascade
4. This results in more AMPA receptors
being implanted in the post-synaptic
membrane making the connection smoother
in the short term
5. For persistent LTP dopamine needs to be
present. This is released from another cell
signalling that this ‘memory’ is important.
Long term LTP
6. Proteins are then synthesised that stabilise the new AMPA
receptors to make the LTP long term • Cofiring / Stimulus
• NMDA receptor activation
• Dopamine
• Protein Synthesis
1
,The Memory Engram
An engram is the network of neurons that
represent the memory.
Memory Consolidation
Semantic and episodic memory overlap to
create knowledge networks. The semantic
knowledge is based on many episodic
memories. However you don’t remember then
totally.
The brain knows when to keep memories
when certain things occur more often.
Patient H.M. – Bilateral removal of hippocampus – heavy anterograde amnesia and temporally
graded retrograde amnesia.
Interventional Techniques
• Lesions – permanent
• Optogenetics – fast
• Pharmacology – slow
Observational Techniques
Impossible to talk about causality using these methods
• FMRI
• 2-Deoxy-Glucose-Imaging
System consolidation is rapidly accelerated once you
already have similar knowledge. For instance you know
the environment but not the location of a specific reward
this will be a lot easier to learn because you have a map of
the area in memory.
Example
People who have a great knowledge of Nijmegen will
remember an address for a longer time then people less
familiar with Nijmegen.
Inhibition of the prefrontal cortex while learning new information Techniques:
you will not be able to remember this new information. Immediate early gene measurements
Pharmacology
2
,3
, Lecture 2 Single Cell Electrophysiology
• Networks of neurons come together to build the maps in the brain.
• In the cerebral cortex they are organized in cortical columns.
• In the mouse, each column has ~12K neurons, making ~12M connections, and ~100K glia
across the ~6 cortical layers.
• Layers have distinct distribution of neurons and different input/output relationship with
local and distant networks, creating circuit motifs
The action potential (in case you haven’t seen this a million times)
1. All is fine and basic
2. The membrane is depolarized by input
3. Na+ channels open – spike
4. Na+ channels close – K+ channels open
5. Membrane potential goes down to basic (overshoots a little because
aiming is hard)
Extracellular recording
• As opposed to intracellular methods, extracellular methods enable neural recording by
measuring changes in voltage in the vicinity of the cell body, rather than inside the cell
body.
• The shape of the potential measured depends on the electrodes proximity to the cell
Methods for recording
Tetrode
• An electrode can pick up a spike as far as 140um away
from the source
• Given spikes of different cells do not vary much,
multiple electrodes are needed in the vicinity of the
action potential to enable single-unit isolation
• Tetrode is made up of fine (<30um) wires separated
~20-50um apart
Probes
• Electrode probes capitalise on the spatial layout of a
tetrode while increasing dramatically channel yield
• Importantly, the increase in channels does not lead to a
proportional increase in the probe size (tissue damage
is limited)
4
One of the most fundamental idea’s of memory and
memory consolidation.
• Episodic = Memories about an event in your life
• Semantic = Facts
Memory Consolidation
Memory = the combined activity of a network that spans
a whole brain
• The hippocampus – Important for memory consolidation
• The Cortex – location the memory is stored
When you consolidate a memory you make it independent on the
hippocampus. Then it will be more dependant on certain area’s of the
cortex depending on the specific
When you are sleeping your brain sort through to see which memories
are important to keep and in what detail.
Memory consolidation – days to weeks
Cellular Consolidation Cellular Consolidation – in hours
Cells that wire together, fire together
1. When cells are activated at the same time
a lot the AMPA receptors activate and
depolarise
2. Mg block is gone from the NMDA
receptors and influx of Ca rapidly increase
3. CaMKII phosphorylates AMPA receptors
and stars a cascade
4. This results in more AMPA receptors
being implanted in the post-synaptic
membrane making the connection smoother
in the short term
5. For persistent LTP dopamine needs to be
present. This is released from another cell
signalling that this ‘memory’ is important.
Long term LTP
6. Proteins are then synthesised that stabilise the new AMPA
receptors to make the LTP long term • Cofiring / Stimulus
• NMDA receptor activation
• Dopamine
• Protein Synthesis
1
,The Memory Engram
An engram is the network of neurons that
represent the memory.
Memory Consolidation
Semantic and episodic memory overlap to
create knowledge networks. The semantic
knowledge is based on many episodic
memories. However you don’t remember then
totally.
The brain knows when to keep memories
when certain things occur more often.
Patient H.M. – Bilateral removal of hippocampus – heavy anterograde amnesia and temporally
graded retrograde amnesia.
Interventional Techniques
• Lesions – permanent
• Optogenetics – fast
• Pharmacology – slow
Observational Techniques
Impossible to talk about causality using these methods
• FMRI
• 2-Deoxy-Glucose-Imaging
System consolidation is rapidly accelerated once you
already have similar knowledge. For instance you know
the environment but not the location of a specific reward
this will be a lot easier to learn because you have a map of
the area in memory.
Example
People who have a great knowledge of Nijmegen will
remember an address for a longer time then people less
familiar with Nijmegen.
Inhibition of the prefrontal cortex while learning new information Techniques:
you will not be able to remember this new information. Immediate early gene measurements
Pharmacology
2
,3
, Lecture 2 Single Cell Electrophysiology
• Networks of neurons come together to build the maps in the brain.
• In the cerebral cortex they are organized in cortical columns.
• In the mouse, each column has ~12K neurons, making ~12M connections, and ~100K glia
across the ~6 cortical layers.
• Layers have distinct distribution of neurons and different input/output relationship with
local and distant networks, creating circuit motifs
The action potential (in case you haven’t seen this a million times)
1. All is fine and basic
2. The membrane is depolarized by input
3. Na+ channels open – spike
4. Na+ channels close – K+ channels open
5. Membrane potential goes down to basic (overshoots a little because
aiming is hard)
Extracellular recording
• As opposed to intracellular methods, extracellular methods enable neural recording by
measuring changes in voltage in the vicinity of the cell body, rather than inside the cell
body.
• The shape of the potential measured depends on the electrodes proximity to the cell
Methods for recording
Tetrode
• An electrode can pick up a spike as far as 140um away
from the source
• Given spikes of different cells do not vary much,
multiple electrodes are needed in the vicinity of the
action potential to enable single-unit isolation
• Tetrode is made up of fine (<30um) wires separated
~20-50um apart
Probes
• Electrode probes capitalise on the spatial layout of a
tetrode while increasing dramatically channel yield
• Importantly, the increase in channels does not lead to a
proportional increase in the probe size (tissue damage
is limited)
4
