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Although cholinergic cells make up only a small fraction of the total population, the striatum has one of the highest acetylcholine concentrations of any brain structure.
In vivo, this form of regulation of ACh synthesis would be controlled by neurotransmitters released by neurons that innervate particular cholinergic cells.
Abnormalities in the PLD-mediated release of choline would be expected to result in an impairment of cholinergic neurotransmission and/or in a generalized malfunction of cholinergic cells.
However, our observations that PLD1 overexpression increases ACh production form endogenous sources suggest that PLD1 may serve the same function as PLD2 in other cholinergic cells.
It will also be important to determine how cholinergic cells regulate the metabolism of PA - a compound with multiple signaling and structural functions - when the PLD pathway is stimulated to meet the demand for choline.
Despite representing less than 1% of the total population of accumbal neurons, these cholinergic cells are able to control the activity of the dopaminergic terminals that innervate medium spiny neurons (MSNs) in the nucleus accumbens.
The interactions of aminergic inhibitory neurons and cholinergic excitatory neurons can be measured, and REM sleep occurs when aminergic cells are at their least active and cholinergic cells are at their most active.
The most serious and troublesome side effects of these classical antipsychotics are movement disorders that resemble the symptoms of Parkinson's disease, because the neuroleptics antagonize dopamine receptors broadly, also reducing the normal dopamine-mediated inhibition of cholinergic cells in the striatum.
These data show that SN56 cells express exclusively PLD2 and thus experimental manipulations of the activity of this PLD isoform were subsequently employed to determine if this enzyme is capable of producing choline for ACh synthesis in cholinergic cells.
Although it is clear that the PLD-generated choline is efficiently utilized by cholinergic cells (LA-N-2 and SN56) as a precursor of ACh, the quantitative significance of this pathway and mechanisms that regulate it remain to be fully determined.