Hypothalamic proopiomelanocortin (POMC) neurons have a cholinergic phenotype

Neuronal networks originating in the hypothalamic arcuate nucleus play fundamental roles in the control of energy balance. Neuropeptide Y (NPY)‐producing neurons in the arcuate nucleus stimulate food intake, whereas arcuate nucleus neurons that release the proopiomelanocortin (POMC)‐derived peptide α‐melanocyte‐stimulating hormone (α‐MSH) potently reduce food intake. Relatively little attention has been focused on classical neurotransmitters in regulation of food intake. Here, we have investigated the potential presence of acetylcholine (ACh) in NPY‐ and POMC‐containing neuronal populations of the arcuate nucleus. Antisera to proteins required for cholinergic neurotransmission, including choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT), were employed in double‐labeling immunohistochemical experiments. In colchicine‐treated rats, ChAT‐ and VAChT‐immunopositive cell bodies were located in the ventral aspect of the arcuate nucleus. ChAT and VAChT immunoreactivities were demonstrated in α‐MSH‐ and cocaine‐ and amphetamine‐regulated transcript (CART)‐containing cell bodies of the arcuate nucleus, whereas cell bodies containing NPY or agouti‐related peptide (AGRP) were distinct from VAChT‐immunoreactive neuronal perikarya. VAChT immunoreactivity was also present in a large number of α‐MSH‐containing nerve fiber varicosities throughout the central nervous system. In the commissural part of the nucleus tractus solitarius, no α‐MSH‐containing cell bodies were found to have ChAT or VAChT immunoreactivity. The presence of markers for cholinergic neurotransmission in a subpopulation of hypothalamic POMC/CART neurons suggests co‐release of ACh with peptides derived from the POMC precursor and CART. The results indicate a role for ACh in control of energy balance, mediating the effects of peripheral hormones such as leptin and insulin.