Loss of Stk11 in basolateral amygdalar projection neurons impairs taste aversion learning by altering the temporal pattern of taste response plasticity in gustatory cortex

Abstract

Gustatory cortex (GC) responds to tastes on the tongue with dynamic ensemble activity that represents first the presence, then the identity, and finally the hedonic value (palatability) of tastes. This final state of the taste response is uniquely altered by conditioned taste aversion (CTA) -- a powerful one-trial learning paradigm in which a taste becomes aversive after association with gastric malaise -- a process requiring coordination between GC and basolateral amygdala (BLA). One key requirement for learning in this circuit is expression of the serine/threonine kinase 11 (Stk11) gene (a tumor suppression gene which has only recently been associated with learning). When Stk11 is knocked out in BLA projection neurons (BLApn), CTA learning fails to occur. Here we have examined how learning-related response plasticity in GC taste responses is impacted by the knockout of Stk11 in BLApn. Contrary to the commonly held assumption that a lack of learning means a lack of such plasticity, but consistent with the fact that Stk11KO has been shown to increase the excitability of BLApn, our data reveal that the knockout of Stk11 in BLApn does not eliminate plasticity; rather, it shifts the impact of CTA training on GC taste responses to an earlier, learning-inappropriate epoch. Even naïve taste representations are altered -- specifically, the pattern of similarities and differences among the different taste responses are rendered abnormal by Stk11 KO, and these relationships fail to change with training. Finally, the latency of behavior-related dynamic ensemble features of the GC taste response, which is also abnormal in naïve KO mice, is rendered disorganized by CTA. Together, these results suggest that Stk11 plays a role in governing the coordination of GC activity by BLA, and demonstrate that alterations in the function of BLApn caused by Stk11KO inhibit learning not by inhibiting plasticity but by changing its temporal properties.

Neural correlates of rapid familiarization to novel taste

“…To extract the temporal structure of ensemble activity on the scale of single-trials, we fit Poisson HMMs to spike trains from simultaneously-recorded units (Jones et al, 2007; Moran and Katz, 2014; Nanu et al, 2021). We fit separate models for each tastant for each recording session from 0ms to 2000 ms peri-stimulus, with 2-6 states connected in a feed-forward manner.…”