Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise

Abstract

Objective

Hypothalamic Pro-opiomelanocortin ( POMC) and Neuropeptide Y/Agouti-Related Peptide ( NPY/ AgRP) neurons are critical nodes of a circuit within the brain that sense key metabolic cues as well as regulate metabolism. Importantly, these neurons retain an innate ability to rapidly reorganize synaptic inputs and electrophysiological properties in response to metabolic state. While the cellular properties of these neurons have been investigated in the context of obesity, much less is known about the effects of exercise training.

Methods

In order to further investigate this issue, we utilized neuron-specific transgenic mouse models to identify POMC and NPY/AgRP neurons for patch-clamp electrophysiology experiments.

Results

Using whole-cell patch-clamp electrophysiology, we found exercise depolarized and increased firing rate of arcuate POMC neurons. The increased excitability of POMC neurons was concomitant with increased excitatory inputs to these neurons. In agreement with recent work suggesting leptin plays an important role in the synaptic (re)organization of POMC neurons, POMC neurons which express leptin receptors were more sensitive to exercise-induced changes in biophysical properties. Opposite to effects observed in POMC neurons, NPY neurons were shunted toward inhibition following exercise.

Conclusions

Together, these data support a rapid reorganization of synaptic inputs and biophysical properties in response to exercise, which may facilitate adaptations to altered energy balance and glucose metabolism.

Highlights

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  Exercise inhibited arcuate NPY neurons.

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  Exercise activated arcuate POMC neurons.

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  Leptin receptor expressing POMC neurons are much more sensitive to response to exercise.

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  Exercise effects are transient, lasting only hours for NPY, while sustainable for days in POMC neurons.