Unsupervised Restoration of a Complex Learned Behavior After Large-Scale Neuronal Perturbation

Abstract

Reliable execution of behaviors requires that brain circuits correct for variations in neuronal dynamics. Genetic perturbation of the majority of excitatory neurons in a brain region involved in song production in adult songbirds with stereotypical songs triggered severe degradation of their songs. The song fully recovered within two weeks, and substantial improvement occurred even when animals were prevented from singing during the recovery period, indicating that offline mechanisms enable recovery in an unsupervised manner. Song restoration was accompanied by increased excitatory synaptic inputs to unmanipulated neurons in the same region. A model inspired by the behavioral and electrophysiological findings suggests that a combination of unsupervised single-cell and population-level homeostatic plasticity rules can support the observed functional restoration after large-scale disruption of networks implementing sequential dynamics. In the model the sequence is restored through a parallel homeostatic process, rather than regrown serially, and predicts that sequences should recover in a saltatory fashion. Correspondingly, we observed such recovery in the songs of manipulated animals, with syllables that rapidly alternate between abnormal and normal durations from rendition to rendition until eventually they permanently settled into their original length. These observations indicate the existence of cellular and systems-level restorative mechanisms that ensure behavioral resilience.

Resilience of A Learned Motor Behavior After Chronic Disruption of Inhibitory Circuits

“…These findings suggest a relationship between the behavioral timeline of recovery, and the return to control-like offline electrophysiological activity. These results suggest that the restoration of excitation/inhibition (E/I) balance and circuit function is mediated by unsupervised mechanisms, consistent with our earlier publication 24 .…”

“…We wondered if the mechanisms of behavioral recovery in an adult are similar depending on whether the activity of excitatory or inhibitory neurons is selectively perturbed. In a previous publication, we observed that permanent genetic muting with TeTN of a large fraction of projection neurons in HVC led to a degraded song, which recovered in around 2 weeks 12 . In this work, we observe that permanent genetic muting of a large fraction of interneurons also leads to degradation and recovery of the song, albeit the recovery takes around 2 months in this case.…”

“…Our previous publication with genetic silencing of projection neurons showed a temporary degradation of the song that recovered within about 2 weeks 12–14 . However, we observed that after genetic muting of HVC interneurons, the song was completely degraded at 2-3 weeks, and bore no resemblance to the original song.…”

“…In the 30-70 Hz range, deflections were different between all animals (p=7.9*10-5 between controls, p<10-40 between all other pairs). The deflections across all animals and frequencies become more similar by 60 dpi (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30).1371 between controls, p<10-6 between all other pairs; 30-70 Hz: p=0.7493 between controls, p<10-2 between all other pairs). For details on statistics see Methods.…”