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Centre for Integrative Physiology Research Briefings Are Neuropeptides Brain Hormones? NEURONS USE MANY NEUROTRANSMITTERS VERSUS neuron, including nerve endings, DIFFERENT CHEMICAL NEUROPEPTIDES somata and dendrites. Indeed, SIGNALS TO COMMUNICATE Neuropeptides are a large and typically 85% of the peptide content INFORMATION, INCLUDING important class of messenger is in the dendrites. The release MORE THAN 100 DIFFERENT molecules that carry information mechanisms for dendritic between neurons in the brain. There neuropeptide release can be very are at least 100 different different from axon terminal release, neuropeptides in the mammalian and for vasopressin and oxytocin, brain, and most of these are made in differentially regulated release allows and released from the hypothalamus. peptide effects in the body to be Some are released into the blood, independent from peptide effects in with peripheral effects as endocrine the brain. PEPTIDES. MANY OF THESE NEUROPEPTIDES EVOKE SPECIFIC AND COHERENT BEHAVIOURS AND HAVE BEEN LINKED TO A NUMBER OF NEUROLOGICAL DISORDERS. INCREASINGLY, WE ARE RECOGNISING THAT PEPTIDE hormones. Of these, the magnocellular vasopressin and SECRET MESSAGE VERSUS SIGNALS PLAY A ROLE IN oxytocin neurons have proved to be PUBLIC ANNOUNCEMENT INFORMATION PROCESSING a good model system for revealing Neuropeptides usually interact with G THAT IS QUITE UNLIKE THAT important aspects of many neuronal protein-coupled receptors to activate OF CONVENTIONAL functions, including neuropeptide intrasignalling pathways that can NEUROTRANSMITTERS. release. The classical way that affect many different aspects of cells. neurons communicate with each Neuropeptides often act back on their other is by neurotransmitter cells of origin, for example to molecules that are packaged in small facilitate the development of vesicles that are released at patterned electrical activity. They can synapses between neurons. However, also act on their neighbours to bind neuropeptides are packaged the collective activity of a neural separately from neurotransmitters, population into a coherent signalling and are released by different entity. Finally, the co-ordinated mechanisms from many parts of a population output can transmit waves of peptide secretion that act as a patterned hormonal Mike Ludwig, PhD Professor of Neurophysiology Tel: +44 (0)131 650 3275 Email: [email protected] analogue signal within the brain. At their distant targets, peptides can reprogramme neural networks, by effects on gene expression, synaptogenesis, and by functionally rewiring connections by substrate for prolonged behavioural disorder, depression, schizophrenia priming activity-dependent release. effects. and autism spectrum disorder. In Classical neurotransmitters pass addition, disorders of appetite “whispered secrets” from one NEUROPEPTIDES AND regulation, libido, and mood are particular cell to another; they carry BEHAVIOUR among many potential targets of a message that matters only at a Many different peptides evoke peptide-based therapies. In the particular time and a particular place. specific effects on behaviour. For future, ‘sniffing’ neuropeptide By contrast, neuropeptides are example, oxytocin is involved in analogues (intranasal administration) “public announcements”, the social behaviours, including bonding may open a gateway to the brain, messages endure, at least for a and maternal behaviour, and and diffusion of the peptides to its while; they are messages not from vasopressin acts in the brain to affect receptor sites may be an alternative one cell to another, but from one social recognition and aggression. way for treatment of some of these population of neurones to another – Other nerve cells release other disorders. these are hormone-like signals. peptides and they have effects on other emotions and behaviours. PRIMING OF RELEASE Evidence of the hormonal nature of In the hypothalamus, large amounts the behaviour effects of peptides of oxytocin and vasopressin are comes from experiments involving released from neuronal dendrites gene manipulation, either through independently of release from nerve transgenic mutations or viral gene terminals. Dendritic peptide release transfer, showing that behavioural can be modulated by priming. traits accompany alterations in the Priming involves making vesicles distribution of peptide receptor readily available for subsequent expression. Thus, it appears that it is activity-dependent release, thus not the distribution of fibres of enhancing the capacity for the local peptidergic neurons in the brain that interactions that co-ordinate determines particular behaviours, but neuronal activity. By enhancing the distribution of the peptide intercommunication, peptides can receptors. “reprogram” the behaviour of a It is now time to bridge the insights neuronal system. Peptides might also emerging from studies of social prime target areas within the brain cognition and social behaviour in which harbour their receptors, animals to human research. triggering a cascade of temporary Vasopressin and oxytocin have been functional reorganisation of the linked to human neurological neuronal networks, providing the disorders such as social anxiety Selected references: Leng G & Ludwig M (2008) Neurotransmitters and peptides: whispered secrets and public announcements. J Physiol 586: 5625-5632. Ludwig M & Leng G (2006) Dendritic neuropeptide release and peptide dependent behaviours. Nat Rev Neurosci 7: 126-136 Ludwig M & Pittman QJ. (2003) Talking back: dendritic neurotransmitter release. Trends Neurosci 26: 255-261 Ludwig M, et al. (2002) Intracellular calcium stores regulate activity-dependent release from dendrites. Nature 418: 85-89 “Dendritic neurotransmitter release”. Ed: M. Ludwig, Springer, New York, 2005 ISBN: 978-0-387-22933-1 Nov 2012