What do you do when counting sheep just doesn’t cut it? Look at neurocircuitry!

Most of us can attest to having trouble getting a good night’s sleep from time-to-time. We lie awake worrying about something that happened during the day, or the room is the wrong temperature or a scary movie we just watched seems a little too plausible. These little disturbances are common, but if you have trouble sleeping most nights there may be a more serious problem. According to the Centers for Disease Control and Prevention (CDC), 70 million Americans suffer from chronic sleep problems.  Sleep is a complex process influenced by many neurotransmitters and hormones.

Figure 1.  A simplified representation of sleep-wake neurocircuitry shows the major brain centers and neuroendocrine parameters involved.  Thick arrows represent active pathways during sleep.  The absence of daylight leads to a net inhibition of excitatory efferent projections to central and peripheral systems active during wakefulness.  Green arrows are excitatory pathways, red are inhibitory pathways.  Abbreviations: 5-HT-Serotonin, Ach-Acetylcholine, ACTH-Adrenocorticotropic hormone, AD-Adrenaline (Epinephrine), Cort-Cortisol, CRF-Corticotropin-releasing factor, DA-Dopamine, DMH-Dorsal medial hypothalamus, DRN-Dorsal raphe nucleus, GABA-Gamma-aminobutyric acid, Glut-Glutamate, HA-Histamine, HCRT-Hypocretin (orexin) neuropeptide precursor, LC-Locus ceruleus, LH-Lateral hypothalamus, Mela-Melatonin, MRN-Medial raphe nucleus, NE/NA-Norepinephrine/Noradrenaline, PVN-Paraventricular nucleus, RVLM-Rostral ventrolateral medulla, SCN-Hypothalamic suprachiasmatic nucleus, TMN-Tuberomammillary nucleus, VLPO-Ventral lateral preoptic area, VTA-Ventral tegmental area

Figure 1. A simplified representation of sleep-wake neurocircuitry shows the major brain centers and neuroendocrine parameters involved. Thick arrows represent active pathways during sleep. The absence of daylight leads to a net inhibition of excitatory efferent projections to central and peripheral systems active during wakefulness. Green arrows are excitatory pathways, red are inhibitory pathways.
Abbreviations: 5-HT-Serotonin, Ach-Acetylcholine, ACTH-Adrenocorticotropic hormone, AD-Adrenaline (Epinephrine), Cort-Cortisol, CRF-Corticotropin-releasing factor, DA-Dopamine, DMH-Dorsal medial hypothalamus, DRN-Dorsal raphe nucleus, GABA-Gamma-aminobutyric acid, Glut-Glutamate, HA-Histamine, HCRT-Hypocretin (orexin) neuropeptide precursor, LC-Locus ceruleus, LH-Lateral hypothalamus, Mela-Melatonin, MRN-Medial raphe nucleus, NE/NA-Norepinephrine/Noradrenaline, PVN-Paraventricular nucleus, RVLM-Rostral ventrolateral medulla, SCN-Hypothalamic suprachiasmatic nucleus, TMN-Tuberomammillary nucleus, VLPO-Ventral lateral preoptic area, VTA-Ventral tegmental area

During the day, wake-promoting brain centers in the brain such as the hypothalamic suprachiasmatic nucleus (SCN), tuberomammillary nucleus (TMN) or locus ceruleus (LC) use excitatory neurotransmitters such as glutamate, histamine, and norepinephrine to keep us awake (Figure 1).  Sleep is the result of a signal cascade that starts when the brain senses a lack of sunlight to the eye.  When the brain senses darkness, inhibitory neurotransmitters and hormones including GABA, serotonin, and melatonin reduce the activity of the wake-promoting brain centers.

Imbalances in neurotransmitters and hormones can lead to excessive activity in the wake-promoting brain centers.  This can contribute to sleep difficulties.  Neurotransmitters and hormones can become imbalanced by a number of different factors including stress, poor diet, infections, toxins, and hypersensitivities.

If your patients are not getting their healthy dose of quality sleep each night, assessing their neurotransmitter and hormone imbalances can provide the information required to develop personalized treatments for their sleep difficulties.

References:
Black, J, et al. (2005). Sleep and Wakefulness: Neurophysiologic Pathways and Pharmacologic Targets. A CME-Certified Monograph.
Chou, TC, et al. (2003). Journal of Neuroscience, 23(33):10691-702.
Freeman, DA, et al. (2007). Behav Neurosci, 121(40):689-97.
Lechin, F, et al. (2002). Neurocircuitry and Neuroautonomic Disorders: Reviews and Terapeutic Strategies. Basel (Switzerland): S. Karger AG.
Pace-Schott, EF, et al. (2002). Chapter 128: Basic Mechanisms of Sleep, In Davis, KL, et al (Eds.), Neuropsychopharmacology: The Fifth Generation of Progress (1859-1877).
Saper, CB, et al. (2005). Nature, 437(27):1257-63.
Simonneaux, V, et al. (2003). Pharmacol Rev, 55(2):352-95.
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One Response to What do you do when counting sheep just doesn’t cut it? Look at neurocircuitry!

  1. Pingback: Norepinephrine: responsible for focus, mood, energy…and sleep? | The NEI Connection

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