Figure 3.

Bottom‐up gamma in bipolar disorder. Afferent input helps activate PPN neurons that manifest intrinsic gamma band oscillations through high threshold, voltage‐dependent calcium channels. These cells project to the intralaminar thalamus (ILT)89, 90 that also manifests these calcium channels to drive cortical activity by terminating in layers I and II. When NCS‐1 is over expressed (NCS‐1 with multiple ++), these oscillations are reduced, but Li⁺ therapy (Li⁺ + NCS‐1) will restore intrinsic gamma band oscillations, perhaps both in the PPN (left side, red records) and ILT (right side, blue records), among other regions. We assume that too much Li⁺ will over inhibit NCS‐1 and decrease oscillations, while too little Li⁺ will not overcome the suppression of oscillations by over expressed NCS‐1. This suggests, in keeping with standard therapy, that concentrations of Li⁺ should be maintained at an optimal level [Colour figure can be viewed at wileyonlinelibrary.com]