Molecular Annotation of Integrative Feeding Neural Circuits

Abstract

SUMMARY The identity of higher-order neurons and circuits playing an associative role to control feeding is unknown. We injected pseudorabies virus, a retrograde tracer, into masseter muscle, salivary gland and tongue of BAC-transgenic mice expressing GFP in specific neural populations and identified several CNS regions that project multi-synaptically to the periphery. MCH and orexin neurons were identified in the lateral hypothalamus, and Nurr1 and Cnr1 in the amygdala and insular/rhinal cortices. Cholera Toxin-β tracing showed that insular Nurr1+ and Cnr1+ neurons project to the amygdala or lateral hypothalamus, respectively. Finally we show that cortical Cnr1+ neurons show increased Cnr1 mRNA and c-Fos expression after fasting, consistent with a possible role for Cnr1+ neurons in feeding. Overall, these studies define a general approach for identifying specific molecular markers for neurons in complex neural circuits. These markers now provide a means for functional studies of relevant neurons in feeding or other complex behaviors.

Cellular and molecular basis of decision‐making

“…However, optogenetic stimulation of MCH neurons alone is not sufficient to alter behaviour in the absence of taste , suggesting that these neurons are components of a reward‐encoding network that integrates information from multiple sources, including the nutrients, lingual taste buds and, possibly, other sites of glucose sensing, such as the gut. Consistent with this possibility, viral tracing from lingual taste buds shows that MCH neurons are part of a circuit processing gustatory information . This is also consistent with the requirement for both sweet taste and optogenetic activation of MCH neurons to drive reward.…”

Deletion of Melanin Concentrating Hormone Receptor-1 disrupts overeating in the presence of food cues

“…This includes the gustatory cortex, the ventroposteromedial thalamus and the parabrachial nucleus [16]. In addition, using retrograde viral tracers, descending projections from LH MCH neurons to peripheral sites critical for orosensory stimulation (masseter muscle and submandibular salivary gland) have been revealed [38]. Moreover, MCH-1R is densely expressed within the nucleus accumbens shell (ACB S ), a reward area thought to influence hedonic eating or so-called 'liking' of food [39].…”

Convergent neuronal projections from paraventricular nucleus, parabrachial nucleus, and brainstem onto gastrocnemius muscle, white and brown adipose tissue in male rats

“…There is some precedent for the concept of convergent target tissue innervation involving muscles and other tissues. For example, Pérez et al () delineated the hierarchy of the anatomical connections among diverse brain regions involved in motor and autonomic elements of feeding. To begin to establish the molecular identity of the neurons that compose these circuits, they injected PRV into masseter muscle, salivary gland, and tongue of mice and identified several CNS regions that project multisynaptically to these organs, including both double (pairwise) as well as triple labeled neurons.…”