PT  - JOURNAL ARTICLE
AU  - Maria Medalla
AU  - Joshua P. Gilman
AU  - Jing-Yi Wang
AU  - Jennifer I. Luebke
TI  - Strength and diversity of inhibitory signaling differentiates primate anterior cingulate from lateral prefrontal cortex
AID  - 10.1523/JNEUROSCI.3757-16.2017
DP  - 2017 Apr 05
TA  - The Journal of Neuroscience
PG  - 3757-16
4099  - http://www.jneurosci.org/content/early/2017/04/05/JNEUROSCI.3757-16.2017.short
4100  - http://www.jneurosci.org/content/early/2017/04/05/JNEUROSCI.3757-16.2017.full
AB  - The lateral prefrontal cortex (LPFC) and anterior cingulate cortex (ACC) of the primate play distinctive roles in the mediation of complex cognitive tasks. Compared to the LPFC, integration of information by the ACC can span longer timescales and requires stronger engagement of inhibitory processes. Here, we reveal the synaptic mechanism likely to underlie these differences, using in vitro patch-clamp recordings of synaptic events and multi-scale imaging of synaptic markers in rhesus monkeys. While excitatory synaptic signaling does not differ, the level of synaptic inhibition is much higher in ACC than LPFC layer 3 pyramidal neurons- with a ∼6x higher frequency and significantly longer duration of inhibitory synaptic currents. The number of inhibitory synapses and the ratio of cholecystokinin to parvalbumin-positive inhibitory inputs are also significantly higher in ACC compared to LPFC neurons. Thus, inhibition is functionally and structurally more robust and diverse in ACC than in LPFC, resulting in a lower excitatory:inhibitory ratio and a greater dynamic range for signal integration and network oscillation by the ACC. These differences in inhibitory circuitry likely underlie the distinctive network dynamics in ACC and LPC during normal and pathological brain states.SIGNIFICANCE STATEMENTThe lateral prefrontal cortex (LPFC) and anterior cingulate cortex (ACC) play temporally distinct roles during the execution of cognitive tasks (rapid working memory during ongoing tasks, long-term memory to guide future action, respectively). Compared to LPFC-mediated tasks, ACC-mediated tasks can span longer timescales and require stronger engagement of inhibition. This study shows that inhibitory signaling is much more robust and diverse in the ACC than in the LPFC. Thus, there is a lower excitatory:inhibitory synaptic ratio and a greater dynamic range for signal integration and oscillatory behavior in the ACC. These significant differences in inhibitory synaptic transmission form an important basis for the differential timing of cognitive processing by the LPFC and ACC in normal and pathological brain states.