Trends in Biomedical Science

Making Memory

The following slides are mostly derived from

The Brain from Top to Bottom, an Interactive Website about the Human Brain and Behavior http://thebrain.mcgill.ca/flash/index_a.html

Every time you learn something, neural circuits are altered in your brain.

When you learn something, it is these synapses whose efficiency increases.

Nerve impulses can more easily travel along a particular circuit.

For example, You hear a new word.You make new connections

among neurons in your brain.Neurons in your visual cortex will

recognize the spelling.Neurons in your auditory cortex

will hear the pronunciation.Neurons in the associative

regions of the cortex will relate the word to your existing knowledge.

Neurons in the visual cortex are making stronger connections.

PLASTICITY IN NEURAL NETWORKS

Learning depends on the plasticity of the circuits in the brain - the ability of the neurons to make lasting changes in the efficiency of their synaptic transmission.

We can say the brain stores information in networks of modified synapses (the arrangement makes the information) and to retrieve this information by activating these networks.

If two neurons are active at the same time, the synapses between them are made stronger.

LONG-TERM POTENTIATION (LTP) was discovered in the hippocampus and has been found in many regions of the cortex.

LTP can cause the long-term strengthening of the synapses between two neurons that are activated simultaneously.

LTP can cause the long-term strengthening of the synapses between two neurons that are activated simultaneously.

Here is a synapse between two neurons.

http://thebrain.mcgill.ca/flash/i/i_07/i_07_m/i_07_m_tra/i_07_m_tra.html

After single stimulus.

Glutamate is a major excitatory neurotransmitter that is associated with learning and memory.

Glutamate is also thought to be associated with Alzheimer’s disease, whose first symptoms include memory malfunctions.

Glutamate, the neurotransmitter released into these synapses, binds to several different receptors on the post-synaptic neuron. Two of these, the receptors for AMPA and NMDA, are especially important for LTP.

The AMPA receptor is paired with an ion channel so that when glutamate binds to this receptor, this channel lets sodium ions enter the post-synaptic neuron.

The sodium causes the post-synaptic dendrite to become locally depolarized, and if this depolarization reaches the threshold to trigger an action potential, the nerve impulse is transmitted to the next neuron.

The NMDA receptor is also paired with an ion channel, but this lets calcium ions into the post-synaptic cell.

When this cell is at resting potential, the calcium channel is blocked by magnesium ions (Mg2+), so that even if glutamate binds to the receptor, calcium cannot enter the neuron.

For these magnesium ions to leave the channel, the dendrite’s membrane potential must be depolarized.

During the high-frequency stimulation that causes LTP: the sustained activation of its AMPA receptors makes the post-synaptic neuron depolarized. The magnesium then leaves the NMDA receptors and allows large numbers of calcium ions to enter the cell.

This increased concentration of calcium in the dendrite starts several biochemical reactions that make this synapse more efficient for an extended period.

These calcium ions are extremely important intracellular messengers that activate many enzymes by altering their shape.

There is a cascade of biochemical reactions which can have many different effects.

http://thebrain.mcgill.ca/flash/a/a_07/a_07_m/a_07_m_tra/a_07_m_tra.html

LTP involves at least two phases: establishment (or induction), which lasts about an hour, and maintenance (or expression), which may last for several days.

The first phase can be experimentally induced by a single, high-frequency stimulation. It involves the activity of various enzymes (kinases) that continue after the calcium is eliminated, but no protein synthesis.

For the maintenance phase a series of high-frequency stimuli must be applied.

This phase needs the synthesis of new proteins - for example, the ones that form the receptors and the ones that contribute to the growth of new synapses (that also occurs during the maintenance phase).

LONG-TERM DEPRESSION

Long-term depression (LTD) may return potentiated synapses in the hippocampus to a normal level so that they will be available to store new information.

But in other parts of the brain, LTD may be actively responsible for the storage of new information, eg in the cerebellum.

LTD develops when a presynaptic neuron is active at low frequencies (1 to 5 Hz) without the postsynaptic neuron’s being subjected to strong depolarization, as it is with LTP.

This raises the concentration of calcium in the postsynaptic neuron, but much less than in LTP.

So, instead of proteins such as kinases being activated, enzymes called phosphatases are activated. These enzymes remove certain phosphate groups from the AMPA receptors; in other words, they dephosphorylate them.

An AMPA receptor subunit has two sites that can be phosphorylated (by CaM kinase II, and PKA).

These sites on the receptor seem to be the target for phosphatases.

In the hippocampus, the dephosphorylation of the AMPA receptor reduces the amplitude of the postsynaptic potential to the normal level where it was before LTP.

It is also believed that the number of AMPA receptors decreases during LTD. These receptors would be removed from the postsynaptic membrane.

Long term depression (LTD)

The following questions can be done as a gap fill exercise on https://dl.dropboxusercontent.com/u/56510853/MakingMemory2-part1.htm

Every time you learn something, _________ circuits are altered in your brain.

Every time you learn something, neural circuits are altered in your brain.

When you learn something, it is these synapses whose ____________ ___________.

Nerve impulses can more easily travel along a particular circuit.

When you learn something, it is these synapses whose efficiency increases.

Nerve impulses can more easily travel along a particular circuit.

For example, You hear a new word.You make new ___________ among

neurons in your brain.Neurons in your ________ cortex

will recognize the spelling.Neurons in your ________ cortex

will hear the pronunciation.Neurons in the __________

regions of the cortex will relate the word to your existing knowledge.

For example, You hear a new word.You make new connections

among neurons in your brain.Neurons in your visual cortex will

recognize the spelling.Neurons in your auditory cortex

will hear the pronunciation.Neurons in the associative

regions of the cortex will relate the word to your existing knowledge.

Neurons in the visual cortex are making stronger connections.

PLASTICITY IN NEURAL NETWORKS

Learning depends on the _________ of the circuits in the brain - the ability of the neurons to make ________ _________ in the efficiency of their synaptic transmission.

Learning depends on the plasticity of the circuits in the brain - the ability of the neurons to make lasting changes in the efficiency of their synaptic transmission.

We can say the brain ________ ___________ in _________ of __________ ____________ (the arrangement makes the information) and to ________ this information by _________ these networks.

We can say the brain stores information in networks of modified synapses (the arrangement makes the information) and to retrieve this information by activating these networks.

If two _________ are _______ at the ____ _____, the synapses between them are made stronger.

If two neurons are active at the same time, the synapses between them are made stronger.

LONG-TERM POTENTIATION (LTP) was discovered in the _____________ and has been found in many regions of the cortex.

LTP can cause the long-term ____________ of the ___________ between two neurons that are _____________ simultaneously.

LONG-TERM POTENTIATION (LTP) was discovered in the hippocampus and has been found in many regions of the cortex.

LTP can cause the long-term strengthening of the synapses between two neurons that are activated simultaneously.

LTP can cause the long-term strengthening of the synapses between two neurons that are activated simultaneously.

LTP can cause the long-term strengthening of the synapses between two neurons that are activated simultaneously.

Here is a synapse between two neurons.

After single stimulus.

Glutamate is a major excitatory ___________ that is associated with _________ and _________.

Glutamate is a major excitatory neurotransmitter that is associated with learning and memory.

Glutamate is also thought to be associated with ___________r’s disease, whose first symptoms include __________ malfunctions.

Glutamate is also thought to be associated with Alzheimer’s disease, whose first symptoms include memory malfunctions.

Glutamate, the neurotransmitter released into these synapses, binds to several different ________ on the post-synaptic _______. Two of these, the receptors for AMPA and NMDA, are especially important for ___.

Glutamate, the neurotransmitter released into these synapses, binds to several different receptors on the post-synaptic neuron. Two of these, the receptors for AMPA and NMDA, are especially important for LTP.

The AMPA receptor is paired with an ion channel so that when _______ binds to this receptor, this channel lets ______ ions enter the post-synaptic neuron.

The AMPA receptor is paired with an ion channel so that when glutamate binds to this receptor, this channel lets sodium ions enter the post-synaptic neuron.

The sodium causes the post-synaptic dendrite to become locally __________, and if this depolarization reaches the __________ to trigger an _____ ________, the nerve impulse is transmitted to the next neuron.

The sodium causes the post-synaptic dendrite to become locally depolarized, and if this depolarization reaches the threshold to trigger an action potential, the nerve impulse is transmitted to the next neuron.

The NMDA receptor is also paired with an ion channel, but this lets calcium ions into the post-synaptic cell.

The NMDA _______ is also paired with an ion channel, but this lets _______ ions into the post-synaptic cell.

When this cell is at _______ ________, the calcium channel is ________ by __________ ions (Mg2+), so that even if glutamate binds to the receptor, calcium cannot enter the neuron.

When this cell is at resting potential, the calcium channel is blocked by magnesium ions (Mg2+), so that even if glutamate binds to the receptor, calcium cannot enter the neuron.

For these magnesium ions to leave the channel, the dendrite’s membrane potential must be ___________.

For these magnesium ions to leave the channel, the dendrite’s membrane potential must be depolarized.

During the high-__________ stimulation that causes LTP: the sustained __________ of its ______ receptors makes the post-synaptic neuron __________. The ___________ then leaves the ______ receptors and allows large numbers of ________ ions to enter the cell.

During the high-frequency stimulation that causes LTP: the sustained activation of its AMPA receptors makes the post-synaptic neuron depolarized. The magnesium then leaves the NMDA receptors and allows large numbers of calcium ions to enter the cell.

This increased concentration of calcium in the dendrite starts several ____________ reactions that make this synapse more _________ for an ___________ period.

This increased concentration of calcium in the dendrite starts several biochemical reactions that make this synapse more efficient for an extended period.

These ________ ions are extremely important intracellular ___________ that _________ many _________ by altering their shape.

There is a ________ of biochemical reactions which can have many different effects.

These calcium ions are extremely important intracellular messengers that activate many enzymes by altering their shape.

There is a cascade of biochemical reactions which can have many different effects.

http://thebrain.mcgill.ca/flash/a/a_07/a_07_m/a_07_m_tra/a_07_m_tra.html

LTP involves at least two phases: ___________ (or induction), which lasts about an hour, and ______________ (or expression), which may last for several days.

LTP involves at least two phases: establishment (or induction), which lasts about an hour, and maintenance (or expression), which may last for several days.

The first phase can be experimentally induced by a single, high-__________ stimulation. It involves the _________ of various ________ (kinases) that continue after the calcium is eliminated, but no ________ synthesis.

The first phase can be experimentally induced by a single, high-frequency stimulation. It involves the activity of various enzymes (kinases) that continue after the calcium is eliminated, but no protein synthesis.

For the _____________ phase a __________ of high-frequency stimuli must be applied.

This phase needs the _________ of new proteins - for example, the ones that form the ________ and the ones that contribute to the growth of new _________ (that also occurs during the maintenance phase).

For the maintenance phase a series of high-frequency stimuli must be applied.

This phase needs the synthesis of new proteins - for example, the ones that form the receptors and the ones that contribute to the growth of new synapses (that also occurs during the maintenance phase).

LONG-TERM DEPRESSION

The following questions can be done as a gap fill exercise on https://dl.dropboxusercontent.com/u/56510853/MakingMemory2-part2.htm

Long-term ____________ (LTD) may return potentiated __________ in the __________ to a normal level so that they will be available to store new information.

Long-term depression (LTD) may return potentiated synapses in the hippocampus to a normal level so that they will be available to store new information.

But in other parts of the brain, LTD may be actively responsible for the storage of new information, eg in the _____________.

But in other parts of the brain, LTD may be actively responsible for the storage of new information, eg in the cerebellum.

LTD develops when a presynaptic neuron is active at low ___________ (1 to 5 Hz) without the ___________ neurons being subjected to strong _____________, as it is with LTP.

LTD develops when a presynaptic neuron is active at low frequencies (1 to 5 Hz) without the postsynaptic neuron’s being subjected to strong depolarization, as it is with LTP.

This _______ the concentration of calcium in the postsynaptic neuron, but much ________ than in LTP.

This raises the concentration of calcium in the postsynaptic neuron, but much less than in LTP.

So, instead of proteins such as kinases being activated, enzymes called phosphatases are _________. These enzymes remove certain _________ groups from the _________ receptors; in other words, they __________ them.

So, instead of proteins such as kinases being activated, enzymes called phosphatases are activated. These enzymes remove certain phosphate groups from the AMPA receptors; in other words, they dephosphorylate them.

An AMPA _________ ______ has two sites that can be _______________ (by CaM kinase II, and PKA).

These sites on the receptor seem to be the target for ______________.

An AMPA receptor subunit has two sites that can be phosphorylated (by CaM kinase II, and PKA).

These sites on the receptor seem to be the target for phosphatases.

In the hippocampus, the __________________ of the AMPA receptor _______ the amplitude of the postsynaptic ________ to the normal level where it was before LTP.

In the hippocampus, the dephosphorylation of the AMPA receptor reduces the amplitude of the postsynaptic potential to the normal level where it was before LTP.

It is also believed that the __________ of AMPA receptors _________ during LTD. These receptors would be removed from the postsynaptic membrane.

It is also believed that the number of AMPA receptors decreases during LTD. These receptors would be removed from the postsynaptic membrane.

Long term depression (LTD)

Describe what happens to your neural circuits when you learn a new word.

What happens to the efficiency of the circuits?

What does learning depend on?

How does the brain store information?

Draw a diagram showing when synapses between neurons would be made stronger.

What is LONG-TERM POTENTIATION (LTP)?

Use this diagram as a basis to explain LTP

What is glutamate?

What are two of the important receptors that glutamate binds to and seem to be important for LTP?

What does the AMPA receptor do?

Then what happens?

What does the NMDA receptor do?

Then what happens?

What happens with an increased concentration of calcium in the dendrite?

http://thebrain.mcgill.ca/flash/a/a_07/a_07_m/a_07_m_tra/a_07_m_tra.html

Describe the phases of LTP.

Why might we have long-term depression (LTD)?

How does LTD develop?

What are the enzymes activated to begin LTD?

What does the dephosphorylation of the AMPA receptor do?

What happens to the number of AMPA receptors during LTD?

Describe what this picture is showing.