[6] There are two types of CaM kinases: CaMKII accounts for 1–2% of all proteins in the brain,[7][8] and has 28 different isoforms.

Initially, the enzyme is activated; however, autophosphorylation does not occur because there is not enough calcium or calmodulin present to bind to neighboring subunits.

As greater amounts of calcium and calmodulin accumulate, autophosphorylation occurs leading to persistent activation of the CaMKII enzyme for a short period of time.

The close proximity of these adjacent rings increases the probability of phosphorylation of neighboring CaMKII enzymes, furthering autophosphorylation.

LTP is initiated when the NMDA receptors are in a local environment with a voltage potential high enough to displace the positively-charged Mg2+ ion from the channel pore.

She induced LTP in hippocampal slices and experimentally applied an antagonist (CaMKIINtide) to prevent CaMKII from remaining active.

The slices that were applied with CaMKIINtide showed a decrease in Normalized EPSP slope after the drug infusion, meaning that the induced LTP reversed itself.

When CaMKII is infused in postsynaptically in the hippocampal slices and intracellular perfusion or viral expression, there is a two- to threefold increase in the response of the synapse to glutamate and other chemical signals.

Movement of AMPA receptors increases postsynaptic response to presynaptic depolarization through strengthening the synapses.

In addition to increasing the channel conductance of GluA1 subunits, CaMKII has also been shown to aid in the process of AMPA receptor exocytosis.

CaMKII can stimulate the endosomes to move to the outer membrane and activate the embedded AMPA receptors.

The greater number of AMPA receptors increases the sensitivity of the synapse to presynaptic depolarization, and generates LTP.

In 1998, Giese and colleagues studied knockout mice that have been genetically engineered to prevent CaMKII autophosphorylation.

They observed that mice had trouble finding the hidden platform in the Morris water maze task.

The mice's inability to find the hidden platform implies deficits in spatial learning.

[29] Irvine and colleagues in 2006 showed that preventing autophosphorylation of CaMKII cause mice to have impaired initial learning of fear conditioning.

[32] Mayford and colleagues engineered transgenic mice that express CaMKII with a point mutation of Thr-286 to aspartate, which mimics autophosphorylation and increases kinase activity.

[33] Researchers speculate these results could be due to lack of stable hippocampal place cells in these animals.

It is possible with viral vector delivery to inject a specific gene of choice into a particular region of the brain in an already developed animal.

Studies have found that knockout mice without CaMKIIA demonstrate a low frequency of LTP.