Learning & Memory: Cellular Changes
Fall 2002

We will use a broad definition of learning: a change in behavior as a result of experience.

Most learning appears to occur at the synapse. Thus, the minimum requirement for learning is a neural circuit that has two neurons. These two neurons could change in three ways:

1) change in the presynaptic neuron (e.g., altered transmitter release)
2) change in the postsynaptic neuron (e.g., altered sensitivity of receptors)
3) create new connections between neurons
Difficult to test these mechanisms in humans because there are 100 billion neurons.
Thus, simple types of learning have been studied in simple animals (e.g., invertebrates). Simple types of learning include (Figures 20.1 & 20.2):
  Habituation: Decreased response to a stimulus with repeated exposure

Sensitization: Enhanced response following a strong stimulus

Classical Conditioning: The development of a conditioned response (CR) to a conditioned stimulus (CS) by repeated pairing with an unconditioned stimulus (US) (see Figure 20.2).
 
 

The neural mechanisms for these types of learning have been studied in a large sea slug (size of a fist) called Aplysia (Figure 20.3)
The advantage of using aplysia is that there are relatively few neurons (20,000) so the changes associated with habituation, sensitization, and classical conditioning can be studied.
 

Habituation is the simplest type of learning. All it requires is:

A sensory neuron to bring information in.
A motor neuron to execute movements.

The change that occurs with habituation could be in the sensory neuron or the motor neuron. Data show that:

1. The activity of the sensory neuron does not change with repeated stimulation.
2. Repeated electrical stimulation of the motor neuron gives withdrawal every time.

Thus, the change must be in the connection between the sensory and motor neurons. There is a reduction in presynaptic Ca++ entry with repeated stimulation so the sensory neuron releases less neurotransmitter (Figures 20.6 & 20.7).
 
 

Sensitization requires an interneuron in addition to the sensory and motor neurons.
Electric shock activates the interneuron which releases serotonin on the presynaptic terminal of the sensory neuron. Serotonin causes K+ channels to close which prolongs the action potential (i.e., K+ can't escape) causing more transmitter to be released. This is called presynaptic facilitation (Figures 20.8, 20.9 & 20.10).


Classical Conditioning requires only three neurons.

Similar to sensitization except closing of K+ channel is mediated by a second messenger which produces longer lasting effects (Figures 20.11 & 20.12).


Proposed neural mechanisms for classical conditioning in mammals includes:

Long term depression (LTD): a decrease in response by pairing stimuli.
Long term potentiation (LTP): an increase in response by pairing stimuli.


For example, neurons in the hippocampus show enhanced activity following a strong input (i.e., LTP). The enhanced activity persists for up to weeks and is believed to contribute to transfering memories to the cortex. LTP occurs in CA1 pyramidal cells in the hippocampus (Figure 20.17). That is, weak inputs to CA1 neurons become stronger when paired with another input (Figures 20.18 & 20.9). This requires several steps and special glutamate receptors known as NMDA receptors (Figure 20.20):

1. NMDA receptors have channels that are normally blocked by magnesium (Mg+)
2. Strong depolarization of the CA1 pyramidal cell dislodges the Mg++
3. Glutamate binds to the NMDA receptor and allows Ca++ to pass through the channel
4. Ca++ changes intracellular proteins which enhance other glutamate receptors
5. Activation of the previously weak synapse now produces a much bigger effect through these changed glutamate receptors.
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