Au Yong, N. | Search bioRxiv

bioRxiv2024

Spinal interneuron population dynamics underlying flexible pattern generation

The mammalian spinal locomotor network is composed of diverse populations of interneurons that collectively orchestrate and execute a range of locomotor behaviors. Despite the identification of many classes of spinal interneurons constituting the locomotor network, it remains unclear how the networks collective activity computes and modifies locomotor output on a step-by-step basis. To investigate this, we analyzed lumbar interneuron population recordings and multi-muscle electromyography from spinalized cats performing air stepping and used artificial intelligence methods to uncover state space trajectories of spinal interneuron population activity on single step cycles and at millisecond timescales. Our analyses of interneuron population trajectories revealed that traversal of specific state space regions held millisecond-timescale correspondence to the timing adjustments of extensor-flexor alternation. Similarly, we found that small variations in the path of state space trajectories were tightly linked to single-step, microvolt-scale adjustments in the magnitude of muscle output. One sentence summaryFeatures of spinal interneuron state space trajectories capture variations in the timing and magnitude of muscle activations across individual step cycles, with precision on the scales of milliseconds and microvolts respectively.

neuroscience↗

bioRxiv2023

GABAergic synaptic scaling is triggered by changes in spiking activity rather than transmitter receptor activation.

Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought to be a likely candidate to homeostatically control spiking activity. However, recent findings have forced us to reconsider this idea as several studies suggest AMPAergic scaling is not directly triggered by changes in spiking. Moreover, studies examining homeostatic perturbations in vivo have suggested that GABAergic synapses may be more critical in terms of spiking homeostasis. Here we show results that GABAergic scaling can act to homeostatically control spiking levels. We found that perturbations which increased or decreased spiking in cortical cultures triggered multiplicative GABAergic upscaling and downscaling, respectively. In contrast, we found that changes in AMPAR or GABAR transmission only influence GABAergic scaling through their indirect effect on spiking. We propose that GABAergic scaling represents a stronger candidate for spike rate homeostat than AMPAergic scaling. Significance StatementThe nervous system maintains excitability in order to perform network behaviors when called upon to do so. Networks are thought to maintain spiking levels through homeostatic synaptic scaling, where compensatory multiplicative changes in synaptic strength are observed following alterations in cellular spike rate. Although we demonstrated that AMPAergic synaptic scaling does not appear meet these criteria as a spike rate homeostat, we now show that GABAergic scaling could play this role. Here we present evidence that the characteristics of GABAergic scaling place it in an excellent position to be a spiking homeostat. This work highlights the importance of inhibitory circuitry in the homeostatic control of excitability. Further, it provides a point of focus into neurodevelopmental disorders where excitability is impaired.

neuroscience↗