The process of learning begins with sensory signals being transcribed in the cortex.

They are then transmitted to the hippocampus where new memories are believed to form.

If a signal is strong, or repeated, a long-term memory is established and wired back to the

cortex for storage.

Lesions in the hippocampus impair formation of new memories, but do not affect the older

ones.

The brain consists of billions of neurons.

Neurons communicate with each other through a space between them, called a synapse.

A typical neuron can have thousands of synapses, or connections, with other neurons.

Together, they form extremely complex networks that are responsible for all brain’s functions.

Synaptic connections can change over time, a phenomenon known as synaptic plasticity.

Synaptic plasticity follows the “use it or lose it” rule: frequently used synapses

are strengthened while rarely used connections are eliminated.

Synaptic plasticity is believed to underlie the process of learning and memory retention.

New memories are formed when neurons establish new connections, or STRENGTHEN existing synapses.

If a memory is no longer needed or rarely recalled, its corresponding synapses will

slowly weaken and eventually disappear.

The strength of a synapse is measured by the level of excitability or responsiveness of

the post-synaptic neuron in response to a GIVEN stimulus from the pre-synaptic neuron.

High-frequency signals or repeated stimulations STRENGTHEN synaptic connections over time.

This is known as long-term potentiation, or LTP, and is thought to be the cellular basis

of memory formation.

LTP can occur at most excitatory synapses all over the brain, but is best studied at

the glutamate synapse of the hippocampus.

When a glutamatergic neuron is stimulated, action potentials travel down its axon and

trigger the release of glutamate into the synaptic cleft.

Glutamate then binds to its receptors on the post-synaptic neuron.

The 2 main glutamate receptors that often co-exist in a synapse are AMPA and NMDA receptors.

These are ion channels that activate upon binding to glutamate.

When the pre-synaptic neuron is stimulated by a WEAK signal, only a small amount of glutamate

is released.

Although both receptors are bound by the glutamate, only AMPA is activated by weak stimulation.

Sodium influx through the AMPA channel results in a SLIGHT DE-polarization of the post-synaptic

membrane.

The NMDA channel remains closed because its pore is blocked by magnesium ions.

When the pre-synaptic neuron is stimulated by a STRONG or REPEATING signal, a large amount

of glutamate is released; the AMPA receptor stays open for a longer time, admitting more

sodium into the cell, thus resulting in a GREATER DE-polarization.

Increased influx of positive ions EXPELS magnesium from the NMDA channel, which NOW activates,

allowing not only sodium but also CALCIUM into the cell.

Calcium is the mediator of LTP induction.

There are 2 distinct phases of LTP.

In the early phase, calcium initiates signaling pathways that activate several protein kinases.

These kinases enhance synaptic communication in 2 ways: they phosphorylate the existing

AMPA receptors, thereby increasing AMPA conductance to sodium; and help to bring more AMPA receptors

from intracellular stores to the post-synaptic membrane.

This phase is thought to be the basis of short-term memory, which lasts for several hours.

In the late phase, NEW proteins are made and gene expression is activated to further enhance

the connection between the 2 neurons.

These include newly synthesized AMPA receptors, and expression of other proteins that are

involved in the growth of NEW dendritic spines and synaptic connections.

The late phase may correlate with formation of long-term memory.