Human Physiology/The Nervous System

12

Late Phase

Late LTP is the natural extension of E-LTP. L-LTP requires gene transcription and protein synthesis in the

postsynaptic cell, unlike E-LTP. Late LTP is also associated with the presynaptic synthesis of synaptotagmin and an

increase in synaptic vesicle number, suggesting that L-LTP induces protein synthesis not only in postsynaptic cells,

but in presynaptic cells as well. This is discussed under "retrograde messenger" below.

Induction

Late LTP is induced by changes in gene expression and protein synthesis brought about by persistent activation of

protein kinases activated during E-LTP, such as MAPK. In fact, MAPK--Specifically the ERK subfamily of

MAPKs--may be the molecular link between E-LTP and L-LTP, since many signaling cascades involved in E-LTP,

including CaMKII and PKC, can converge on ERK.

Maintenance

Upon activation, ERK may phosphorylate a number of cytoplasmic and nuclear molecules that ultimately result in

the protein synthesis and morphological changes associated with L-LTP. These chemicals may include transcription

factors such as CREB. ERK-mediated changes in transcription factor activity may trigger the synthesis of proteins

that underlie the maintenance of L-LTP. PKMzeta is one such molecule. When this molecule is inhibited in rats, they

experience retrograde amnesia (where you can't recall previous events but short term memory works fine).

Expression

Aside from PKMzeta, many of the proteins synthesized during L-LTP are unknown. They are though to increase

postsynaptic dendritic spine number, surface area and sensitivity to the neurotransmitter associated with L-LTP

expression.

Retrograde Signaling

Retrograde signaling is a hypothesis that attempts to explain that, while LTP is induced and expressed

postsynaptically, some evidence suggests that it is expressed presynaptically as well. The hypothesis gets its name

because normal synaptic transmission is directional and proceeds from the presynaptic to the postsynaptic cell. For

induction to occur postsynaptically and be partially expressed presynaptically, a message must travel from the

postsynaptic cell to the presynaptic cell in a retrograde (reverse) direction. Once there, the message presumably

initiates a cascade of events that leads to a presynaptic component of expression, such as the increased probability of

neurotransmitter vesicle release.

Retrograde signaling is currently a contentious subject as some investigators do not believe the presynaptic cell

contributes at all to the expression of LTP. Even among proponents of the hypothesis there is controversy over the

identity of the messenger.

Language and Speech

Language depends on semantic memory so some of the same areas in the brain are involved in both memory and

language. Articulation, the forming of speech, is represented bilaterally in the motor areas. However, for most

individuals, language analysis and speech formation take place in regions of the left hemisphere only. The two

regions involved are:

1. Broca's Area
2. Wernicke's Area

Broca's area is located just in front of the voice control area of the left motor cortex. This region assembles the motor

of speech and writing. For example, patients with lesions in this area:

1. Understand language perfectly

2. May be able to write perfectly

3. Seldom speak spontaneously