Ultrastructural evidence for intra‐ and extranuclear projections of GABAergic neurons of the suprachiasmatic nucleus

Buijs, Ruud M.; Hou, Yang-Xun; Shinn, Susan; Renaud, Leo P.

doi:10.1002/cne.903400308

Cited by 123 publications

(100 citation statements)

References 30 publications

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“…This is important as GABA is the main neurochemical used to mediate synaptic transmission within the SCN (Moore and Speh 1993;Buijs et al 1994). Agonists of GABAa receptors phase advance the in vitro SCN of hamsters during the day (Tominaga et al 1994).…”

Section: Discussionmentioning

confidence: 99%

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Circadian clock resetting in the mouse changes with age

Biello

2009

AGE

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The most widely recognised consequence of normal age-related changes in biological timing is the sleep disruption that appears in old age and diminishes the quality of life. These sleep disorders are part of the normal ageing process and consist primarily of increased amounts of wakefulness and reduced amounts of deep sleep. Changes in the amplitude and timing of the sleep-wake cycle appear to represent, at least in part, a loss of effective circadian regulation of sleep. Understanding alterations in the characteristics of stimuli that help to consolidate internal rhythms will lead to recommendations to improve synchronisation in old age. Converging evidence from both human and animal studies indicate that senescence is associated with alterations in the neural structure thought to be primarily responsible for the generation of the circadian oscillation, the suprachiasmatic nuclei (SCN). Work has shown that there are changes in the anatomy, physiology and ability of the clock to reset in response to stimuli with age. Therefore it is possible that at least some of the observed age-related changes in sleep and circadian timing could be mediated at the level of the SCN. The SCN contain a circadian clock whose activity can be recorded in vitro for several days. We have tested the response of the circadian clock to a number of neurochemicals that reset the clock in a manner similar to light, including glutamate, N-methyl-D-aspartate (NMDA), gastrin-releasing peptide (GRP) and histamine (HA). In addition, we have also tested agents which phase shift in a pattern similar to behavioural 'non-photic' signals, including neuropeptide Y (NPY), serotonin (5HT) and gamma-aminobutyric acid (GABA). These were tested on the circadian clock in young and older mice (approximately 4 and 15 months old). We found deficits in the response to specific neurochemicals but not to others in our older mice. These results indicate that some changes seen in the responsiveness of the circadian clock to light with age may be mediated at the level of the SCN. Further, the responsiveness of the circadian clock with age is attenuated to some, but not all stimuli. This suggests that not all clock stimuli loose their effectiveness with age, and that it may be possible to compensate for deficits in clock performance by enhancing the strength of those stimulus pathways which are intact.

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Section: Discussionmentioning

confidence: 99%

“…The SCN receive extensive GABAergic innervation (Buijs et al 1994) and nearly all of the neurones in the SCN are GABA-producing (Moore and Speh 1993). Many phase shifting stimuli are thought to involve GABA in their actions on the circadian clock, and it is likely that it plays a significant role in regulating entrainment.…”

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confidence: 99%

Circadian clock resetting in the mouse changes with age

Biello

2009

AGE

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“…2 B). The nature of the nuclear labelling in GABAergic neurons in the SCN is unclear, both in terms of the identity of the immunoreactive epitopes and the functional implications, as noted also by Buijs et al (1994Buijs et al ( , 1995. Nevertheless, similar marking of GABAergic nuclei in other parts of the brain is regarded as not understood rather than nonspecific (P. Somogyi, personal communication).…”

Section: Gabaergic Somatamentioning

confidence: 99%

“…A number of immunocytochemical studies have shown that GABA appears to be the most ubiquitous neurotransmitter in the SCN (Okamura et al 1989 ;Castel et al 1990 a, b ;Decavel & Van den Pol, 1990 ;Moore & Speh, 1993 ;Buijs et al 1994Buijs et al , 1995Belenky et al 1996). However, less attention has been paid to the heterogeneity of the GABA-containing elements in the SCN, as a possible basis for the multiple roles played by this neurotransmitter in circadian regulation.…”

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confidence: 99%

“…In many SCN neurons, GABA or its synthesising enzyme glutamic acid decarboxylase (GAD), are coexpressed with these neuropeptides (Castel & Cohen, 1991 ;Buijs et al 1994Buijs et al , 1995Tanaka et al 1997 ;Pennartz et al 1998 b). Although colocalisation of peptides with GABA in the central nervous system is widespread (Somogyi et al 1985), the robust peptide\GABA association in the SCN may have a special significance for circadian physiology (Tanaka et al 1997).…”

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Morphological heterogeneity of the GABAergic network in the suprachiasmatic nucleus, the brain's circadian pacemaker

Castel

Morris

2000

Journal of Anatomy

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GABA (gamma-amino-butyric acid) is the predominant neurotransmitter in the mammalian suprachiasmatic nucleus (SCN), with a central role in circadian time-keeping. We therefore undertook an ultrastructural analysis of the GABA-containing innervation in the SCN of mice and rats using immunoperoxidase and immunogold procedures. GABA-immunoreactive (GABA-ir) neurons were identified by use of anti-GABA and anti-GAD (glutamic acid decarboxylase) antisera. The relationship between GABA-ir elements and the most prominent peptidergic neurons in the SCN, containing vasopressin-neurophysin (VP-NP) or vasoactive intestinal polypeptide (VIP), was also studied. Within any given field in the SCN, approximately 40-70 % of the neuronal profiles were GABA-ir. In GABA-ir somata, immunogold particles were prominent over mitochondria, sparse over cytoplasm, and scattered as aggregates over nucleoplasm. In axonal boutons, gold particles were concentrated over electron-lucent synaptic vesicles (diameter 40-60 nm) and mitochondria, and in some instances over dense-cored vesicles (DCVs, diameter 90-110 nm). GABA-ir boutons formed either symmetric or asymmetric synaptic contacts with somata, dendritic shafts and spines, and occasionally with other terminals (axo-axonic). Homologous or autaptic connections (GABA on GABA, or GAD on GAD) were common. Although GABA appeared to predominate in most neuronal profiles, colocalisation of GABA within neurons that were predominantly neuropeptide-containing was also evident. About 66 % of the VIP-containing boutons and 32 % of the vasopressinergic boutons contained GABA. The dense and complex GABAergic network that pervades the SCN is therefore comprised of multiple neuronal phenotypes containing GABA, including a wide variety of axonal boutons that impinge on heterologous and homologous postsynaptic sites.

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Differences in colocalization between Fos and PHI, GRP, VIP and VP in neurons of the rat suprachiasmatic nucleus after a light stimulus during the phase delay versus the phase advance period of the night

et al. 1996

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Two groups of four rats each received a 15-minute light stimulus during the first part of the night (ZT14) and the second part (ZT19), respectively. After 45-60 minutes, the animals were killed by perfusion fixation. Adjacent Vibratome sections through the suprachiasmatic nucleus (SCN) were double-immunostained for the presence of peptide histidine isoleucine (PHI), gastrin releasing peptide (GRP) or vasoactive intestinal peptide (VIP) with Fos by using fluorophore-conjugated secondary antibodies. A few sections were triple-immunostained for PHI, GRP or VIP with vasopressin (VP) and Fos. Sections were analyzed with a confocal laser scanning microscope. It turned out that the ZT19 light stimulus induced 4.2 times more nuclear profiles in the SCN immunoreactive for Fos than the light stimulus given at ZT14. The SCN of control animals did not show any Fos immunoreactivity. After the ZT14 light stimulus, approximately 33% of the Fos profiles showed colocalization with a perikaryal profile immunoreactive for PHI, GRP or VIP, whereas at ZT19, this percentage had doubled to approximately 65%. After the light stimulus at ZT14, the relatively low Fos induction was numerically and proportionally most prominent in the PHI-immunoreactive perikarya. As compared with ZT14, the increase of Fos after the ZT19 light stimulus was most pronounced in the GRP-immunoreactive perikarya (21x) followed by VIP (15x) and PHI (5x). This outcome suggests that at least three different cell groups characterized by, respectively, PHI alone, GRP, and VIP fully or partly colocalized with PHI, play a prominent role during light-induced phase shifts: the PHI neurons during light-induced phase delays, the GRP and VIP/(PHI) neurons during light-induced phase advances.

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Ultrastructural evidence for intra‐ and extranuclear projections of GABAergic neurons of the suprachiasmatic nucleus

Cited by 123 publications

References 30 publications

Circadian clock resetting in the mouse changes with age

Circadian clock resetting in the mouse changes with age

Morphological heterogeneity of the GABAergic network in the suprachiasmatic nucleus, the brain's circadian pacemaker

Differences in colocalization between Fos and PHI, GRP, VIP and VP in neurons of the rat suprachiasmatic nucleus after a light stimulus during the phase delay versus the phase advance period of the night

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