Unsupervised restoration of a complex learned behavior after large-scale neuronal perturbation

This paper reports on research investigating how zebra finches recover their complex learned behaviors following large-scale neuronal perturbations. The researchers selectively disrupted the activity of the projection neurons in the HVC (hyperpallium ventralis) region critical for song sequence generation in zebra finches using genetic tools, leading to severe song degradation. Surprisingly, even after being prevented from singing for some time, the zebra finches were able to fully recover their original song within 2 weeks.

Authors and Paper Source: This research was conducted by Bo Wang, Zsofia Torok, Alison Duffy, David G. Bell, Shelyn Wongso, Tarciso A. F. Velho, Adrienne L. Fairhall, and Carlos Lois from the California Institute of Technology. The paper was published in the journal Nature Neuroscience in 2024.

Research Workflow: a) First, the authors used viral vectors to express the bacterial sodium channel NachBac or tetanus toxin light chain (TeTx) in the HVC to disrupt the firing or synaptic release of HVC projection neurons, respectively. In the initial few days after perturbation, the songs were completely degraded and syllables became unrecognizable.

b) Surprisingly, after 5-10 days, the zebra finch songs started to recover, and after approximately 2 weeks, they fully recovered to a level similar to pre-perturbation. The authors quantitatively described the dynamics of song degradation and recovery by analyzing changes in song acoustic features.

c) To investigate the mechanism of song recovery, the authors prevented a group of zebra finches from vocalizing during the recovery period and found that their songs still significantly recovered, suggesting the existence of an offline mechanism independent of practice that facilitated recovery.

d) Through electrophysiological recordings, the authors found a significant increase in excitatory synaptic inputs onto the unperturbed HVC neurons, while the intrinsic properties of these neurons themselves remained unchanged.

e) The authors constructed a computational model simulating neuronal sequence dynamics and found that in addition to single-cell homeostatic mechanisms, a network-level homeostatic mechanism and the recruitment of previously “silent” HVC projection neurons were required to explain the observed increase in synaptic input and behavioral recovery.

Key Findings: 1) After large-scale perturbations, zebra finches can gradually recover their complex singing behavior within 2 weeks through an offline mechanism independent of practice.

2) The recovery process is accompanied by a significant increase in excitatory synaptic inputs onto the unperturbed HVC projection neurons, while the intrinsic properties of these neurons remain unchanged.

3) Based on behavioral and electrophysiological results, both single-cell and network-level homeostatic mechanisms, as well as the recruitment of previously “silent” HVC projection neurons, are required to explain the recovery of sequence dynamics in the neural circuit.

Significance: This study reveals the ability of the brain’s neural circuits to self-reorganize and maintain critical behaviors after large-scale perturbations, highlighting the brain’s unsupervised self-organizing mechanism for recovering sequence dynamics. This finding has important implications for understanding how the brain preserves information and behavioral continuity over the long term and restores neural function after disease or injury.

This research systematically investigated the behavioral dynamics and neural circuit reorganization of zebra finches after perturbation of the song circuit, uncovering intrinsic recovery mechanisms such as neuronal homeostasis and recruitment of new neurons. It provides new insights into the molecular and network basis underlying the brain’s ability to maintain behavioral stability and self-repair.