Postdoc Talks
Chi-Hong Wu
(Turrigiano Lab)
Homeostatic Synaptic Scaling Establishes the Specificity of Aversive Taste Memory
Connections between neurons of the brain can be compared to muscles: the more use they get, the stronger they get. A devoted bodybuilder may focus on one small muscle, trying to increase its size, rather than all the muscles in the arm. Memory formation is similar: learning and memory requires increasing the connection strength at the synapse, the communication spot, between neurons. This process, however, must be scaled in some way, in order to make a memory specific rather than general (that you don’t like white chocolate in particular, not all chocolate, for example). Dr. Wu discussed his work looking at synaptic scaling in taste memory creation and its importance in the development of specified memories.
Hebbian plasticity mechanisms such as long-term potentiation (LTP) are widely considered critical for learning and memory. Nonetheless, LTP can initiate a positive feedback process that, if left unchecked, will pervasively increases synaptic strengths, and result in a failure to achieve memory specificity. Synaptic scaling, a form of homeostatic plasticity, has been theorized to constrain this run-away LTP by globally adjusting post-synaptic strengths and thus ensure faithful encoding of memory. While compelling on theoretical grounds, it has not been tested whether synaptic scaling partners with LTP in vivo during memory formation. Furthermore, the impact of disrupted synaptic scaling on memory fidelity remains unknown. Here we directly examined how synaptic scaling shaped memory specificity in conditioned taste aversion (CTA), a form of associative learning that relies on Hebbian plasticity within the gustatory cortex (GC). We hypothesize that perturbation of synaptic scaling in the GC, the brain region involved in both acquisition and maintenance of CTA, will degrade the stimulus-specificity of CTA.
We first demonstrated that after CTA conditioning, juvenile rats transitioned from a generalized to a taste-specific aversion over a timescale of ~24 hours. Furthermore, the duration of this transient general aversion correlates with the strength of conditioning. To elucidate whether synaptic scaling established the specificity of CTA, we perturbed homeostatic synaptic scaling in vivo using viral vectors to introduce either the C-terminus fragment of GluA2 or a mutant GluA2, both known to block synaptic scaling in vitro. Notably, we found that blocking synaptic scaling in the GC prolonged the phase of CTA-induced general aversion without impairing the acquisition of CTA. This result was further corroborated by a third viral manipulation known to specifically block synaptic downscaling. Next, we found that GC neuronal ensembles active during conditioning were robustly reactivated by the generalized tastant when animals manifested general aversion. Abolishing synaptic scaling in the GC conditioning-active ensembles led to a striking and persistent increase in postsynaptic strengths that correlated with the prolonged general aversion. Taken together, our work establishes that synaptic scaling is important for sculpting the transition from a generalized to a specific state of an associative memory, and that homeostatic regulation of synaptic strengths modulates precise and stable memory formation.