How the Brain Modifies Its Own Circuits: Synaptic Neuromodulation 
lators operate through the cAMP cascade, but the 
specific neuromodulator used in this instance, 
and the particular neuronal pathway employed 
for the neuromodulatory signal, have not yet 
been identified. 
The, experiments described above used neu- 
rons from a particular region of the brain — the 
hippocampus — that were grown in tissue cul- 
ture. In order to be sure that the neuromodula- 
tory mechanisms investigated were not some pe- 
culiarity of cultured neurons, we have also 
demonstrated that the same effects can be found 
in brain slices of the hippocampal region. 
Thus our laboratory has discovered a powerful 
mechanism through which neuronal activity can 
regulate synaptic strength and thereby modify the 
computations carried out by neural circuits. The 
next challenge is to discover how the brain actu- 
ally makes use of this mechanism to switch from 
one compensational state to another. 
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