Learning & Memory

Introduction

Nerve Impulses

Ion Channels

Synaptic Transmission

Learning - Overview

Pavlovian Type

Hebbian Type

Holographic Memory

Comprehension

As discussed in the previous page, the Pavlovian type of learning involves only the presynaptic neuron. In the Hebbian type of learning, the synaptic modification is induced by the participation of both presynaptic and postsynaptic neurons.

Recalling that learning is the ability to associate two events that happen almost at the same time. In the hippocampus, events are represented by a population of neurons, each may be either excited or in the resting state. A particular event is represented by a particular set of neurons in the excited state. For instance, if the number of neurons involved in the representation is n, then mathematically an event can be denoted by a vector with the dimension n, 

X = [x₁, x₂, x₃, .....x_n]

where x_i (i = 1 - n) is either "0" (resting) or "1" (excited). 

The hippocampus contains the most complex neural network. Each neuron is connected to thousands of other neurons. For simplicity, we assume that only five neurons are involved in the representation of events. The connection of these neurons are shown in Figure 16. The lines are drawn from the nerve terminals (presynaptic) in the upper row to the dendrites (postsynaptic) in the lower row. For example, in Figure 16, the terminals of the first neuron are connected to the dendrites of the second and fourth neurons. The terminals of the second neuron are connected to the dendrites of the first and third neurons. These lines may also be considered as the synapses between neurons. The "dark cloud" is represented by the excitation of the second and fourth neurons and the "rain" is represented by the excitation of the first, fourth and fifth neurons.

Figure 16. Illustration of the Hebbian type associative learning. See text for detail.

In the Hebbian type of learning, the synaptic modification may be induced only when both presynaptic and postsynaptic neurons are excited. In Figure 16, these synapses are represented by red lines. The left red line connects the second and first neurons; the right red line connects the fourth and fifth neurons. When the dark cloud and rain happen almost at the same time, these neurons are excited and their synapses are modified so that nerve impulses can be more easily transmitted from the presynaptic neuron to the postsynaptic neuron. Suppose before learning the nerve impulse is unlikely to transmit from the the second neuron to the first neuron. After the pairing between dark cloud and rain, this synaptic transmission is greatly enhanced. Next time, the dark cloud alone is likely to cause the excitation of the first neuron, thereby increasing the probability to recall the rain.

How could the physiological system implement the Hebbian type of learning - namely, excitation of both presynaptic and postsynaptic neurons induces synaptic modification? The answer is the NMDA channel, which is a subtype of glutamate receptor channels. For most synaptic ion channels, activation (opening) requires only the binding of neurotransmitters. However, activation of the NMDA channel requires two events: binding of glutamate (a neurotransmitter) and relief of Mg²⁺ block. NMDA channels are located at the postsynaptic membrane. When the membrane potential is at rest, the NMDA channels are blocked by the Mg²⁺ ions. If the membrane potential is depolarized due to excitation of the postsynaptic neuron, the outward depolarizing field may repel Mg²⁺ out of the channel pore. On the other hand, binding of glutamate may open the gate of NMDA channels (the gating mechanisms of most ion channels are not known). In the normal physiological process, glutamate is released from the presynaptic terminal when the presynaptic neuron is excited. Relief of Mg²⁺ block is due to excitation of the postsynaptic neuron. Therefore, excitation of both presynaptic and postsynaptic neurons may open the NMDA channels.

Another important feature of the NMDA channel is that it conducts mainly the Ca²⁺ ion which may activate various enzymes for synaptic modification. The enhancement of synaptic transmission is called the long-term potentiation (LTP), which involves two parts: the induction and the maintenance. The induction refers to the process which opens NMDA channels for the entry of Ca²⁺ ions into the postsynaptic neuron. The subsequent synaptic modification by Ca²⁺ ions is referred to as the maintenance of LTP. We have just explained the mechanism for the induction of LTP. Mechanisms for the maintenance of LTP have not been fully understood. However, it is known that the AMPA receptor trafficking plays an important role.

The AMPA receptor is a subtype of glutamate receptor. They may form ion channels to conduct small cations.  Their density at the postsynaptic membrane can regulate synaptic strength. Higher density will allow greater ionic influx upon binding of glutamate released from the presynaptic terminal, thereby resulting in more membrane depolarization, which in turn facilitates transmission of the nerve impulse from the presynaptic neuron to the postsynaptic neuron. For this reason, AMPA receptors are continuously being inserted into or removed from the postsynaptic membrane. This AMPA receptor trafficking is controlled by the Ca²⁺ ion. The detailed signaling cascade is given in this review article.