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

Abstract

ObjectiveHypothalamic 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.MethodsIn 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.ResultsUsing 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.ConclusionsTogether, 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.

Intermittent Fasting and High-Intensity Exercise Elicit Sexual-Dimorphic and Tissue-Specific Adaptations in Diet-Induced Obese Mice

“…While the cellular properties of these neurons have been investigated in the context of obesity and diet, much less is known about the effects of exercise training. Recently, repeated bouts of HIIT training (3 × 20 min) demonstrated, in a time-dependent fashion, an inhibitory effect on NPY -expressing neurons while eliciting an overall excitatory effect in adjacent POMC -expressing neurons [ 28 ]. Conversely, others have shown no effect on NPY and POMC mRNAs expression levels and food intake after one month of high-intensity exercise [ 29 ].…”

Acute effects of zinc and insulin on arcuate anorexigenic proopiomelanocortin neurons

“…The 7–9 weeks pathogen‐free male POMC‐hrGFP::LepR‐cre::td‐tomato (POMC‐hrGFP mice RRID: IMSR_JAX:006421; LepR‐cre mice RRID: IMSR_JAX:008320; td‐tomato mice RRID: IMSR_JAX:007908) (He et al ., ; Huang et al ., ; Sohn and Williams, ; Williams et al ., ), POMC‐hrGFP::LepR‐cre::td‐tomato::TRPC5 KO (TRPC5 KO mice RRID: IMSR_JAX:030804) (Gao et al ., ), POMC‐creER::IR‐flox::LepR‐flox::td‐tomato (POMC‐CreER t2 mice RRID: MGI: 5569339, IR‐flox mice RRID: IMSR_JAX:006955, LpeR‐flox mice RRID: IMSR_JAX:018989) and NPY‐hrGFP mice (NPY‐hrGFP mice RRID: IMSR_JAX:006417) (Sun et al, ) were used for all experiments. All mice were housed under standard laboratory conditions (12 h on/off; lights on at 7:00 a.m.) and temperature‐controlled environment.…”

Beneficial metabolic role of β-arrestin-1 expressed by AgRP neurons

“…Brain slices were prepared from young adult male mice (10 to 18 weeks old), as previously described (44,62,63). Briefly, mice were deeply anesthetized with 7% chloral hydrate (i.p.)…”