Synapses with inhibitory neurons differentiate anterior cingulate from dorsolateral prefrontal pathways associated with cognitive control.

Kevan A Martin

Kevan A Martin

Kevan A Martin

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The calbindin-containing inhibitory neurons in area 9 of the dorsolateral prefrontal cortex of the macaque monkey receive excitatory input from the anterior cingulate cortex, whereas the calretinin-containing inhibitory neurons in area 9 receive excitatory input, predominantly from area 46. Area 9 is thought to play a role in working memory and this segregation of input to the different subtypes of GABAergic neurons, as shown in this paper, points to a hitherto unsuspected fine degree of modulation of the inhibitory systems of prefrontal cortex. Connections between cortical areas are made by pyramidal neurons, whose major _target (85%) are other pyramidal cells, with the remaining 15% being GABAergic inhibitory cells, which can be divided into three classes on the basis of their expression of calcium-binding proteins. There is a correlation between the morphology and connections of GABAergic cells and the calcium-binding proteins they express. This is significant because the calretinin-containing cells provide a significant output to other inhibitory cells and so their action is thought to disinhibit pyramidal cells, whereas the calbindin-containing cells inhibit pyramidal cells. Both these inhibitory neurons _target distal dendrites and so are thought to control the input to pyramidal cells, whereas the parvalbumin-containing inhibitory cells _target the proximal portions of pyramidal cells where they are thought to control the output. The authors speculate that the role of these segregated pathways is to exploit signal enhancement at the most active columns, through excitation via the anterior cingulate pathway, and suppress activity in surrounding columns, by the pathway from area 46, thereby improving the signal-to-noise ratio, which is important for working memory.