Homeostatic Regulation of Spike Rate within Bursts in Two Distinct Preparations

Abstract

Homeostatic plasticity represents a set of mechanisms thought to stabilize some function of neural activity. Here, we identified the specific features of cellular or network activity that were maintained after the perturbation of GABAergic blockade in two different systems: mouse cortical neuronal cultures where GABA is inhibitory and motoneurons in the isolated embryonic chick spinal cord where GABA is excitatory (males and females combined in both systems). We conducted a comprehensive analysis of various spiking activity characteristics following GABAergic blockade. We observed significant variability in many features after blocking GABA_A receptors (e.g. burst frequency, burst duration, overall spike frequency in culture). These results are consistent with the idea that neuronal networks achieve activity goals using different strategies (degeneracy). On the other hand, some features were consistently altered after receptor blockade in the spinal cord preparation (e.g. overall spike frequency). Regardless, these features did not express strong homeostatic recoveries when tracking individual preparations over time. One feature showed a consistent change and homeostatic recovery following GABA_A receptor block. We found that spike rate within a burst (SRWB) increased after receptor block in both the spinal cord preparation and cortical cultures, and then returned to baseline within hours. These changes in SRWB occurred at both single cell and population levels. Our findings indicate that the network prioritizes the spiking dynamics within a burst, which appear to be variable under tight homeostatic regulation. The result is consistent with the idea that networks can maintain an appropriate behavioral response in the face of challenges.

Significance statement Homeostatic plasticity plays a critical role in maintaining optimal neural function, particularly during development when the system undergoes repeated functional challenges. In our current study, GABA receptor activity was blocked in two different systems, one in which GABA is inhibitory and another in which GABA is excitatory. In both, we observed that the spike rate within a burst (SRWB) consistently increased and homeostatically returned to control levels in the continued presence of the blocker, demonstrating the importance of SRWB maintenance. When a network is called into action or is functionally engaged during a synaptic barrage, a critical feature that is homeostatically maintained is the spike rate during this activity, which would be crucial for network behavioral performance.