Elsevier

Neuroscience

Volume 119, Issue 4, 16 July 2003, Pages 1209-1219
Neuroscience

Research paper
State-dependent activity of neurons in the perifornical hypothalamic area during sleep and waking

https://doi.org/10.1016/S0306-4522(03)00173-8Get rights and content

Abstract

Neurons containing orexins are located in the perifornical hypothalamic area and are considered to have a role in sleep–wake regulation. To examine how this area is involved in the regulation of sleep and wakefulness, we recorded neuronal activity in undrugged, head-restrained rats across sleep–waking cycles. Recordings were made in the perifornical hypothalamic area where orexin-immunoreactive neurons are distributed (PFH), and in the area dorsal to the PFH, including the zona incerta and subincertal nucleus (collectively referred to as ZI). The 40 neurons recorded from in the PFH were divided into five groups: (1) neurons most active during paradoxical sleep (PS, n=14, 35%), (2) neurons active during both waking (W) and PS (n=12, 30%), (3) neurons most active during W (n=7, 18%), (4) neurons most active during slow-wave sleep (SWS, n=3, 7.5%), and (5) neurons whose activity had no correlation with sleep–waking states (n=4, 10%). Of 30 neurons recorded from in the ZI, the corresponding numbers were 13 (43%), seven (23%), six (20%), three (10%), and one (3.3%). In both areas, neuronal activity fluctuated more during PS than during W. Waking-specific neurons (group 3) in the PFH generated action potentials with longer durations than those produced by other types of neurons. About half of the neurons in the PFH that were classified in groups 1, 2, and 3 increased their firing rate after the transition from one state to another, while higher percentages of neurons of groups 1 and 2 in the ZI than those in the PFH increased their firing rate prior to the state shift from SWS to PS. In these ZI neurons, however, the firing rate varied considerably at the state shift.

These results suggest that the PFH and ZI are involved in the regulation of PS or W, especially the regulation of phasic events during PS or the maintenance of W. The ZI appears to be more closely involved than the PFH in the induction of PS or some phasic phenomena associated with PS.

Section snippets

Experimental procedures

The present study was carried out under the control of the Animal Research Committee in accordance with the Guidelines on Animal Experiments of Fukushima Medical University and the Animal Protection and Management Law of the Japanese Government (No. 105). All efforts were made to minimize animal suffering and to reduce the number of animals used.

Classification of neurons by their behavior

Activity during whole sleep–waking cycles (consisting of W, SWS, and PS) was recorded from 70 neurons. Fig. 1 is an example of recording sites which were marked by Pontamine Sky Blue and were confirmed to be located in a field of orexin-immunoreactive neurons. As shown in Fig. 2, the neurons were divided into five groups according to their firing rates during sleep–waking cycles. P-type neurons (Fig. 2A) were most active during PS and the firing rate during W was lower than or about the same

Discussion

A number of lesion and stimulation studies have revealed that the LHA, including the ZI, is involved in regulation of feeding Oomura et al., 1967, Walsh and Grossman, 1975, McDermott and Grossman, 1979, Rolls, 1984, drinking Mogenson and Stevenson, 1967, Clark et al., 1991, and locomotion Sinnamon and Stopford, 1987, Lammers et al., 1988. There are a large number of lesion or stimulation studies suggesting the role of the LHA in maintaining waking state or arousal Kolb et al., 1979, Stock et

Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research (12680797) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors thank N. Anzai for her technical assistance.

References (60)

  • B. Kolb et al.

    Effects of serial lateral hypothalamic destruction on feeding behavior, body weight, and neocortical and hippocampal EEG activity

    Exp Neurol

    (1979)
  • Y. Koyama et al.

    Firing of neurons in the preoptic/anterior hypothalamic areas in ratits possible involvement in slow wave sleep and paradoxical sleep

    Neurosci Res

    (1994)
  • Y. Koyama et al.

    In vivo electrophysiological distinction of histochemically-identified cholinergic neurons using extracellular recording and labelling in rat laterodorsal tegmental nucleus

    Neuroscience

    (1998)
  • Y. Koyama et al.

    Sensory responsiveness of “broad-spike” neurons in the laterodorsal tegmental nucleus, locus coeruleus and dorsal raphe of awake ratsimplications for cholinergic and monoaminergic neuron-specific responses

    Neuroscience

    (1994)
  • Y. Koyama et al.

    Modulation of presumed cholinergic mesopontine tegmental neurons by acetylcholine and monoamines applied iontophoretically in unanesthetized cats

    Neuroscience

    (2000)
  • J.H. Lammers et al.

    Hypothalamic substrates for brain stimulation-induced patterns of locomotion and escape jumps in the rat

    Brain Res

    (1988)
  • L. Lin et al.

    The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene

    Cell

    (1999)
  • A.D. Loewy

    Forebrain nuclei involved in autonomic control

    Prog Brain Res

    (1991)
  • L.J. McDermott et al.

    Regulation of calorie intake in rats with rostral zona incerta lesionseffects of caloric density or palatability of the diet

    Physiol Behav

    (1979)
  • G.J. Mogenson et al.

    Drinking induced by electrical stimulation of the lateral hypothalamus

    Exp Neurol

    (1967)
  • T. Nambu et al.

    Distribution of orexin neurons in the adult rat brain

    Brain Res

    (1999)
  • T. Ono et al.

    Feeding and diurnal related activity of lateral hypothalamic neurons in freely behaving rats

    Brain Res

    (1986)
  • Y. Oomura et al.

    Neuronal mechanism of feeding

    Prog Brain Res

    (1967)
  • C.B. Saper et al.

    The sleep switchhypothalamic control of sleep and wakefulness

    Trends Neurosci

    (2001)
  • J.E. Sherin et al.

    Activation of ventrolateral preoptic neurons during sleep

    Science

    (1996)
  • H.M. Sinnamon et al.

    Locomotion elicited by lateral hypothalamic stimulation in the anesthetized rat does not require the dorsal midbrain

    Brain Res

    (1987)
  • O.A. Smith et al.

    Functional analysis of hypothalamic control of the cardiovascular responses accompanying emotional behavior

    Fed Proc

    (1980)
  • M. Steriade et al.

    Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems

    J Neurosci

    (1990)
  • G. Stock et al.

    Cardiovascular changes during arousal elicited by stimulation of amygdala, hypothalamus and locus coeruleus

    J Auton Nerv Syst

    (1981)
  • R. Szymusiak et al.

    Preoptic area sleep-regulating mechanisms

    Arch Ital Biol

    (2001)
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