Dendritic peptide release and peptide-dependent behaviours

REVIEWSArcuate nucleusA cell group located in the

mediobasal hypothalamus. It is

involved in regulating the

secretion of prolactin and

growth hormone, and in

appetite and metabolism.PrimingIn this context, priming refers

to the process by which LDCVs

are prepared and made

available for subsequent

activity-dependent release.Small synaptic vesicle

(SSV). A small secretory vesicle

(~50 nm in diameter)

containing neurotransmitters

that are released during

calcium-regulated exocytosis.

Release occurs mainly at the

presynaptic terminal into the

synaptic cleft. Under the

electron microscope, the

vesicle appears clear.Neurons use many chemical signals to communicate

information, including more than 100 different peptides1. In all brain areas there are subsets of neurons

that express particular peptides, but the diversity is

particularly apparent in the hypothalamus, where

many small populations of neurons have distinctive

functional and biochemical phenotypes. In one population of ~3,000 neurons in the arcuate nucleus, three

anorectic peptides are co-expressed: -melanocytestimulating hormone (-MSH), galanin-like peptide,

and cocaine-and-amphetamine-regulated transcript.

In another subpopulation, two orexigenic peptides are

co-expressed: neuropeptide Y (NPY) and agouti-related

peptide (AGRP). These are not the only peptides in the

arcuate nucleus: -endorphin, dynorphin, enkephalin,

galanin, ghrelin, growth hormone-releasing hormone,

neurotensin, neuromedin U and somatostatin are also

expressed in subpopulations of neurons. All of these are

released centrally and act on other neurons by binding

to specific, discretely expressed receptors2. Why are so

many different peptides needed many more than

the number of classical synaptic neurotransmitters?

Increasingly, we are recognizing that peptides have a

role in information processing that is quite unlike that

of conventional neurotransmitters3,4.Many neuropeptides have profound effects on behaviour that are exerted at sites that, in some cases, are rich

in peptide receptors but are innervated by few peptidecontaining projections. Here, we review evidence that

dendrites are a major source of peptides released in the

brain; this release is not specifically targeted at synapses,

and the long half-life of peptides in the CNS and their

abundance in the extracellular fluid mean that, after

release, they can diffuse to distant targets. At their targets, peptides seem to be able to functionally reorganize

neuronal networks, providing a substrate for prolonged

behaviours. One mechanism that might be important in

this remarkable action of neuropeptides is the recently

demonstrated ability of some peptides to prime vesicle

stores for activity-dependent release.Are...