Notes

Defining Learning, Memory and Plasticity

• Plasticity, it allows the acquisition of knowledge/information and the formation of a memory through experience.
• Memory, it is a storage of information that can be recalled at a later stage in time.
• Note, learning results in memory - which has a further outcome - it can change future behavior.

Time - Scales of Synaptic Plasticity

Synaptic Plasticity - A Short Recap of Synaptic Function In the presence of a presynaptic action potential, Calcium channels open allowing an increase of calcium, such that glutamate in vesicles fuses with the synapses and crosses them. Then AMPA are activated and neurotransmitters attach to the receptors. EPSP happens.

Amplitude increases with the number of receiving AMPA channels, hence with LTP the amplitude of EPSP increases due to an increase of neurotransmitters released and received.

Synaptic Plasticity Alters the Intern-Neuron Connection Strength

1. Synaptic Density Size Changes (short term).
2. AMPA/NMDA ratio changes (short term).
3. Number of spines changes (long term).

Note that NMDA stays constant!

Timescales of Neuronal Plasticity

Homeostatic Plasticity, Hebb's Idea & STDP

Necessity of Homeostatic Plasticity Homeostatic plasticity is a mechanism that ensures that the activity of neurons among levels remains constant. It is the process by which the brain adjusts the strength of its synapses to maintain a consistent level of activity. This process helps to balance the overall activity of the brain and maintain a stable internal environment. For example, LTP may occur in response to a particularly strong or meaningful stimulus, resulting in an increase in synapse strength. This increase in strength may be necessary for the formation of a new memory. However, if the increased strength of the synapses were to persist indefinitely, it could lead to an imbalance in activity in the brain. Homeostatic plasticity can help to restore balance by adjusting the strength of other synapses in response to the LTP-induced increase. In this way, LTP and homeostatic plasticity can work together to support the formation of long-term memories while also maintaining the overall stability of the brain.

Papers: "Homeostatic Plasticity in the Developing Nervous System" & "Homeostatic Synaptic Plasticity: Local and Global Mechanism for Stabilizing Neuronal Function".

Homeostatic & Hebbian Plasticity From The Organization of Behavior by Donald Hebb, 1949. "When an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased".

Hebb postulated that this behavior of synapses in neuronal networks would permit the networks to store memories. A Hebbian Synapse is a "coincidence detector".

The first real demonstration of this paradigm can be found in STDP.

Examples of Hebbian Learning - Spike Timing Dependent Plasticity (STDP) STDP represents a form of neural plasticity, it refers to the process by which the strength of a synapse is modified based on the timing of action potentials in the neurons. According to the STDP rule, if an action potential in one neuron (the presynaptic neuron) occurs shortly before an action potential in a second neuron (the postsynaptic neuron), the synapse between the two neurons becomes stronger. On the other hand, if the action potential in the presynaptic neuron occurs after the action potential in the postsynaptic neuron, the synapse becomes weaker.

Papers: "Synaptic Modifications in Cultured Hippocampal Neurons: Dependence on Spike Timing, Synaptic Strength, and Postsynaptic Cell Type" & "Gain in Sensitivity and Loss in Temporal Contrast of STDP by Dopaminergic Modulation at Hippocampal Synapses".

Hebb's Idea How Neurons Can Learn Associations

Hebbian LTD and LTP are Input Specific

1. Cooperativity (induction threshold).
2. Input/Synapse Specificity.
3. Enables Associative Learning.

The weight update is a function H that evaluates time pre and post.

Papers: "Neural Ensemble Dynamics Underlying a Long-Term Associative Memory" & "The Ups and Downs of Hebb Synapses" & "Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules".

What is Geoffrey Hinton's Problem with Hebbian Learning?

One Solution: Three Factor Hebbian Learning Rules The three-factor Hebbian learning rule adds two additional factors to the original Hebbian learning rule:

• Coincidence: the strength of a synapse is only modified if the activity of the two neurons is correlated in time.
• Repetition: the more often the activity of the two neurons is correlated, the greater the effect on the strength of the synapse.
• Intensity: the stronger the activity of the two neurons, the greater the effect on the strength of the synapse.

According to the three-factor Hebbian learning rule, the strength of a synapse is increased when the activity of the two neurons is correlated in time, is repeated, and is strong. Conversely, the strength of a synapse is decreased when the activity of the two neurons is not correlated in time, is not repeated, or is weak.

Heterosynaptic Plasticity

Non-Hebbian Plasticity - Heterosynaptic Plasticity Heterosynaptic Plasticity refers to the process by which the strength of one synapse is modified in response to activity at a different synapse.

Papers: "Is Heterosynaptic Modulation Essential for Stabilizing Hebbian Plasticity and Memory" & "Heterosynaptic Plasticity Underlies Aversive Olfactory Learning in Drosophila".

Homosynaptic vs Heterosynaptic Plasticity There are two broad categories of synaptic plasticity, generally referred to as homosynaptic and heterosynaptic plasticity.

• Homosynaptic plasticity is what we have been discussing with the Hebbian synapses: a synapse-specific strengthening (facilitation) or weakening (depression) based on the activity of pre- and post-synaptic neurons. In fact, the three characteristics: homosynaptic plasticity, associativity and input specificity form the modern definition of the Hebbian synapse.
• Heterosynaptic plasticity refers to synaptic weight adaptation (facilitation or depression) based on the firing of a third modulatory interneuron. It is therefore referred to as non-hebbian plasticity.

In the previous figure: homosynaptic and heterosynaptic mechanisms for long-term plasticity. a) The plastic changes that underlie long-term memory follow a homosynaptic rule, i.e., the events responsible for triggering synaptic strengthening occur at the same synapse as is being strengthened. These changes can result in an increase in synaptic strength or a decrease. b) Synaptic strengthening between a presynaptic and a postsynaptic cell can occur as a result of the firing of a third neuron, a modulatory interneuron, whose terminals end on and regulate the strength of the specific synapse. These changes can result in an increase or in a decrease in synaptic strength.