Abstract
Neural systems use homeostatic plasticity to maintain normal brain functions and to prevent abnormal activity. Surprisingly, homeostatic mechanisms that regulate circuit output have mainly been demonstrated during artificial and/or pathological perturbations. Natural, physiological scenarios that activate these stabilizing mechanisms in neural networks of mature animals remain elusive. To establish the extent to which a naturally inactive circuit engages mechanisms of homeostatic plasticity, we utilized the respiratory motor circuit in bullfrogs that normally remains inactive for several months during the winter. We found that inactive respiratory motoneurons exhibit a classic form of homeostatic plasticity, up-scaling of AMPA-glutamate receptors. Up-scaling increased the synaptic strength of respiratory motoneurons and acted to boost motor amplitude from the respiratory network following months of inactivity. Our results show that synaptic scaling sustains strength of the respiratory motor output following months of inactivity, thereby supporting a major neuroscience hypothesis in a normal context for an adult animal.
Highlights
For the brain to work properly, neurons must employ compensatory mechanisms to retain information in synapses and to maintain normal circuit function
Normal ventilatory behaviors after months of motor inactivity led us to hypothesize that preservation of respiratory motoneuron output from the brainstem to breathing muscles may rely on slow acting, global mechanisms that compensate for neuronal inactivity
Increases in both amplitude and charge transfer of the mEPSC suggest an enhancement of post-synaptic AMPA receptor function rather than changes in dendritic filtering properties of motoneurons (Han and Stevens, 2009). Consistent with this assertion, parameters influencing and influenced by dendritic filtering, neuronal input resistance and mEPSC rise time, respectively, did not differ between control and winter inactivity motoneurons (Figure 2F–G). These results indicate that respiratory motoneurons have enhanced excitatory synaptic strength after winter inactivity presumably by up-regulating postsynaptic function of AMPA-glutamate receptors
Summary
For the brain to work properly, neurons must employ compensatory mechanisms to retain information in synapses and to maintain normal circuit function. Rather than uncovering responses to normal, expected physiological challenges, most investigations of homeostatic plasticity dramatically perturb neuronal activity with artificial (e.g. pharmacological and genetic manipulations) or pathological (e.g. sensory denervation/ stimulation, injury) modalities While these synthetic challenges evoke striking compensatory or homeostatic responses in neurons in vivo (Aizenman et al, 2003; Braegelmann et al, 2017; Echegoyen et al, 2007; Frank, 2014; Gonzalez-Islas and Wenner, 2006; Hengen et al, 2013; Kline et al, 2007; Knogler et al, 2010; Lambo and Turrigiano, 2013; Rajman et al, 2017), how stabilizing mechanisms activated by these kinds of disturbances relate to non-pathological physiological scenarios is unclear, especially in mature animals. As failure to stabilize motor output from the brainstem to respiratory muscles has fatal consequences, these results implicate up-scaling of excitatory synapses on respiratory motoneurons as a critical mechanism for an adult vertebrate experiencing prolonged bouts of neural inactivity in a natural context
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