Functional relationship between forebrain cholinergic projections and somatostatin neurons in the rat

The two neuron types that initially degenerate with Alzheimer's Disease are the cholinergic projections from the septum to the hippocampus and from the substantia innominata to the cortex, and the somatostatinergic neurons in the hippocampus and cortex. The functional relationship between these two types of neurons was investigated using folic acid, a neuro-excitant, and cysteamine, a somatostatin depleter.

Folic acid causes a neuron to fire at a much higher rate than normal (Spector, 1971). Folic acid was injected into either the septum or the substantia innominata, and the long-term effect of the resulting acute hyperactivity of the cholinergic neurons on somatostatin neurons was measured as somatostatin-like immunoreactivity in the hippocampus and cortex. Glutamic acid decarboxylase activity, a marker for gamma-amino butyric acid (GABA) neurons, was also measured because it has been shown to decrease in the cortex after injection of folic acid into the substantia innominata. The administration of folic acid to the cholinergic neurons did not have a significant long-term effect on somatostatin-like immunoreactivity nor glutamic acid decarboxylase activity; therefore, a hyperactivity of the cholinergic neurons did not result in degeneration of GABAergic nor somatostatinergic neurons.

Cysteamine causes a short-term depletion of somatostatin. Cysteamine was injected subcutaneously and the effect of an acute decrease of brain somatostatin on the cholinergic neurons was studied by measuring high affinity choline uptake, an indicator of cholinergic activity. Administration of cysteamine had no measured effect on high affinity choline uptake in the hippocampus or frontal cortex; therefore, a depletion of somatostatin did not effect cholinergic activity. The assay for high affinity choline uptake was tested by injection of pentobarbital, a drug known to decrease high affinity choline uptake. We detected a decrease in high affinity choline uptake after pentobarbital administration, indicating that if cysteamine were decreasing high affinity choline uptake, the assay would have detected it.