CCK-sensitive C fibers activate NTS leptin receptor-expressing neurons via NMDA receptors

Dec 18, 2023American journal of physiology. Regulatory, integrative and comparative physiology

Gut-sensitive nerve fibers activate brainstem neurons with leptin receptors through NMDA receptors

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Leptin receptors in the nucleus of the solitary tract are activated by CCK-sensitive vagal inputs, influencing food intake.

Leptin reduces food intake by acting on both peripheral and central nervous systems.
Knockdown of leptin receptors in specific NTS neurons increases food intake and body weight.
Activation of lepR-expressing neurons by leptin enhances vagal firing through increased NMDA receptor currents.
Monosynaptic inputs from C-type vagal afferents activate lepR neurons, responding to capsaicin.
CCK stimulates spontaneous glutamate release and action potential firing in lepR neurons via its receptors.
In vivo activation of lepR neurons by peripheral CCK is indicated by increased c-fos expression.

AI simplified

The hormone leptin reduces food intake through actions in the peripheral and central nervous systems, including in the hindbrain nucleus of the solitary tract (NTS). The NTS receives viscerosensory information via vagal afferents, including information from the gastrointestinal tract, which is then relayed to other central nervous system (CNS) sites critical for control of food intake. Leptin receptors (lepRs) are expressed by a subpopulation of NTS neurons, and knockdown of these receptors increases both food intake and body weight. Recently, we demonstrated that leptin increases vagal activation of lepR-expressing neurons via increased NMDA receptor (NMDAR) currents, thereby potentiating vagally evoked firing. Furthermore, chemogenetic activation of these neurons was recently shown to inhibit food intake. However, the vagal inputs these neurons receive had not been characterized. Here we performed whole cell recordings in brain slices taken from lepRCre × floxedTdTomato mice and found that lepR neurons of the NTS are directly activated by monosynaptic inputs from C-type afferents sensitive to the transient receptor potential vanilloid type 1 (TRPV1) agonist capsaicin. CCK administered onto NTS slices stimulated spontaneous glutamate release onto lepR neurons and induced action potential firing, an effect mediated by CCKR. Interestingly, NMDAR activation contributed to the current carried by spontaneous excitatory postsynaptic currents (EPSCs) and enhanced CCK-induced firing. Peripheral CCK also increased c-fos expression in these neurons, suggesting they are activated by CCK-sensitive vagal afferents in vivo. Our results indicate that the majority of NTS lepR neurons receive direct inputs from CCK-sensitive C vagal-type afferents, with both peripheral and central CCK capable of activating these neurons and NMDARs able to potentiate these effects. 1

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text ↗

CCK-sensitive C fibers activate NTS leptin receptor-expressing neurons via NMDA receptors

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief