Review
The circadian visual system, 2005

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Abstract

The primary mammalian circadian clock resides in the suprachiasmatic nucleus (SCN), a recipient of dense retinohypothalamic innervation. In its most basic form, the circadian rhythm system is part of the greater visual system. A secondary component of the circadian visual system is the retinorecipient intergeniculate leaflet (IGL) which has connections to many parts of the brain, including efferents converging on targets of the SCN. The IGL also provides a major input to the SCN, with a third major SCN afferent projection arriving from the median raphe nucleus. The last decade has seen a blossoming of research into the anatomy and function of the visual, geniculohypothalamic and midbrain serotonergic systems modulating circadian rhythmicity in a variety of species. There has also been a substantial and simultaneous elaboration of knowledge about the intrinsic structure of the SCN. Many of the developments have been driven by molecular biological investigation of the circadian clock and the molecular tools are enabling novel understanding of regional function within the SCN. The present discussion is an extension of the material covered by the 1994 review, “The Circadian Visual System.”

Section snippets

Introduction and caveats

There have been a large number of new developments with respect to knowledge about the anatomy and physiology of circadian rhythm regulation since publication of our 1994 review, “The Circadian Visual System” (Morin, 1994). As is nearly always the case with such projects, many of the developments were well underway, and in some instances completed, prior to the actual publication of that review. Most notably, much of the presentation in the 1994 review concerning the serotonergic system was

Psychophysics of the circadian rhythm system

The Pickard et al. (1987) IGL lesion paper was one of the first to employ nonsaturating light stimuli to elicit circadian rhythm phase responses. The method eliminated ceiling effects caused by saturating light, providing a more accurate view of psychophysical sensitivity to light, rather than a simple statement that animals respond (or not) to the stimulus. Subsequently, the psychophysics of circadian rhythm phase response to light presented at CT19 has been explored in greater detail. The

Nomenclature

An accepted anatomical nomenclature affords the opportunity to standardize the description of brain structures. This has not yet happened with respect to the SCN intrinsic anatomy. Historically, there have been two approaches to SCN organization, one based on the rat model and the other based on the hamster. The rat SCN has been commonly divided into dorsomedial and ventrolateral divisions. Although these are geographic designations, the conceptualization is based on the fact that, in this

Retinal photoreceptors and projections

In nonmammalian species, the existence of photoreceptors not specialized for classical visual function has long been recognized (Gaston and Menaker, 1968, Menaker, 1968, Menaker and Keatts, 1968, Menaker and Underwood, 1976, Enaker et al., 1970, Underwood and Menaker, 1970). These photoreceptors regulate photoperiodism and entrainment of circadian rhythms in nonmammals. For the same purposes, mammals require photoreceptors in the eye (Foster et al., 2003, Yamazaki et al., 1999). A critical

Glutamate

It is generally believed, based on abundant indirect evidence, that glutamate is the primary neurotransmitter of the retinohypothalamic tract. This topic (up to 1996) has been extensively reviewed (Ebling, 1996, Hannibal, 2002a) and will not be considered in depth here. However, despite the numerous studies of function involving use of glutamate receptor agonists and antagonists, there is much less certainty regarding its actual presence in the RHT. Most convincing in this regard has been the

SCN structure–function relationships

The structure–function relationship that appears to be emerging is one of both time and space. That is to say, the phases of intrinsic oscillatory events vary according to SCN region. Attempts to refine the designation, “region,” according to cell phenotype are progressing, but must be considered as fluid. As is discussed below, the actual number of “regions” in the SCN is highly debatable (2, 3 or even 4 for the rat; Figs. 3A–E), even within a single species, as is the correspondence of a

Humoral factors

One of the more surprising results during the last decade of research on SCN function has been the demonstration that rhythmic events can be controlled, in all likelihood, by nonneural linkage to the circadian clock. The availability of perinatal SCN transplant methods enabled this conclusion. The procedure developed with hamsters by Ralph et al. (1990) used embryonic SCN to restore locomotor rhythms in lesioned, arrhythmic hosts, but SCN efferent connections were restored to an uncertain

Nomenclature

The IGL has been, and continues to be, confused with the ventral lateral geniculate nucleus. Focus on the term, “leaflet,” as a descriptor of the IGL has drawn attention away from the actual boundaries of the nucleus and, until fairly recently, has not had a clearly identifiable homolog in nonrodent species. It is now established that the medial division of the ventral lateral geniculate nucleus is the cat homolog of the IGL (Nakamura and Itoh, 2004, Van der Gucht et al., 2003, Pu and Pickard,

Serotonin and midbrain raphe contribution to circadian rhythm regulation

The 1994 review (Morin, 1994) fell victim to the typical problem of being partially out of date by the time it was published. No topic was more affected by this than serotonin and its effect on circadian rhythmicity. In the year of publication, research on the topic began to blossom and there have been several major reviews published (Morin, 1999, Rea and Pickard, 2000a, Mistlberger et al., 2000, Yannielli and Harrington, 2004).

One of the more important changes in perspective concerning the

Failure to re-entrain

It is axiomatic that an entrained animal will re-entrain to a shifted light–dark cycle. In this era of transgenic animals specifically designed to show abnormal behavioral traits that will allow novel probing of the way things usually work, it is ironic that one of the more provocative developments during the last decade has been the discovery that a standard laboratory rodent, the Siberian hamster, is a model for failure to re-entrain. The initial observation occurred in both young and old

Masking

Mrosovsky (1999) is synonymous with masking and has provided a substantial review of the topic. Masking is important to the study of circadian rhythms for several reasons. One is purely technical to the extent that, under a variety of circumstances in which there are questions concerning whether the evident rhythm is imposed by the environment or is from endogenous sources, tests must be conducted to obtain an explicit answer. For example, mice lacking the genes coding for cryptochrome1 (Cry1)

The future

Circadian rhythmicity is a pervasive feature of mammalian physiology and behavior. Thus, it should not be surprising that discoveries concerning regulation of the circadian visual system have importance with respect to understanding the workings of the brain and body. In this context, the discovery of melanopsin as a photoreceptive molecule in a subset of ganglion cells is one of the great strides forward in the study of the circadian visual system during the last decade. However, as is already

Acknowledgments

Supported by NIH grants NS22168 and MH64471 and National Space Biomedical Research Institute grant HPF0027 via Cooperative Agreement NCC9-58 with the National Aeronautics and Space Administration (to LPM) and NIH grants NS36607 and NS40782 (to CNA).

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